Clinical trial NCT02064387
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma BCMA expressing Lymphomas
Sponsor: GlaxoSmithKline
Start date: 2014-07-29; Completion date: 2019-08-01
Enrollment: 79 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
This study will assess the safety, pharmacokinetic (PK), pharmacodynamic (PD) and the therapeutic potential of GSK2857916 in subjects with multiple myeloma (MM) and lymphomas that express B cell maturation antigen (BCMA). The hypothesis is that GSK2857916 can be safely administered to subjects with MM and with BCMA positive malignancies at doses where target engagement can be demonstrated. This study will determine if adequate target engagement of BCMA receptors translates into clinical benefit for subjects with MM and BCMA positive lymphomas. The study will consists of two parts: a Part 1 dose escalation phase and a Part 2 expansion phase for safety, tolerability, PK, PD, and clinical activity testing. The study will enroll a total of approximately 80-95 subjects with relapsed/refractory MM or BCMA-expressing hematologic malignancies. The maximum dose to be administered in this trial will not exceed 5 milligram/kilogram(mg/kg).

Detailed description:

Arms: arm 1: Participants will receive GSK2857916 intravenously over 60 minutes (one dose) every 3 weeks (21 day cycle) for a maximum of 16 cycles. arm 2: Participants may receive GSK2857916 intravenously over 60 minutes (one dose) once weekly for three consecutive weeks followed by 1 week of rest (28 day cycle) for a maximum of 16 cycles. arm 3: Participants will receive the dose and schedule of GSK2857916 evaluated in Part 1 that is selected for further evaluation in Part 2 for up to 16 cycles. arm 4: Participants may receive the dose and schedule of GSK2857916 evaluated in Part 1 that is selected for further evaluation in Part 2 for a maximum of 16 cycles.
Interventions: intervention 1: GSK2857916
Intervention descriptions: intervention 1: A clear or opalescent solution for IV infusion with unit dose strength of 20 mg/mililiter (mL) for multiple dose levels.

Protocol documents:
SAP_002.pdf: 
CONFIDENTIAL
The GlaxoSmithKline group of companies
BMA117159
1
Division
:
Worldwide Development
Information Type
:
Reporting and Analysis Plan (RAP)
Title
:
DREAMM-1: A Phase I Open-label, Dose Escalation Study 
to Investigate the Safety, Pharmacokinetics, 
Pharmacodynamics, Immunogenicity and Clinical Activity of 
the Antibody Drug Conjugate GSK2857916 in Subjects with 
Relapsed/Refractory Multiple Myeloma and Other Advanced 
Hematologic Malignancies Expressing BCMA
Compound Number 
:
GSK2857916
Effective Date 
:
18-NOV-2019
Description:

The purpose of this RAP is to describe the planned analyses and output to be 
included in the End of Study Clinical Study Report for Protocol GSK Document 
Number 2012N155299_05.

This RAP is intended to describe the safety, clinical activity and pharmacokinetic
analyses required for the study. 

This RAP will be provided to the study team members to convey the content of the 
Statistical Analysis Complete (SAC) deliverable.
RAP Author(s):
Approver
Date
Approval Method
15-NOV-2019
E-mail
Principal Statistician (Oncology, Clinical 
Statistics)
18-NOV-2019
E-mail
Director (Clinical Pharmacology Modelling & 
Simulation)
Copyright 2020 the GlaxoSmithKline group of companies. All rights reserved.  
Unauthorised copying or use of this information is prohibited.
PPD
PPD


CONFIDENTIAL
BMA117159
2
RAP Team Approvals:
Approver
Date
Approval Method
(PPL and Medical Monitor)
16-NOV-2019
E-mail
Director Clinical Development (Oncology, ES 
Clinical)
(OSL)
18-NOV-2019
E-mail
Clinical Development Manager (Oncology, 
Therapy Area Delivery CPSSO Management)
18-NOV-2019
E-mail
Programming Manager (Oncology, Clinical 
Programming)
18-NOV-2019
E-mail
Medical Writing and Clinical Submission 
Planning Director
Clinical Statistics and Clinical Programming Line Approvals:
Approver
Date
Approval Method
18-NOV-2019
E-mail
Senior Statistics Director (Oncology, Clinical 
Statistics)
18-NOV-2019
E-mail
Director Programming (Oncology, Clinical 
Programming)
PPD
PPD
PPD
PPD
PPD
PPD


CONFIDENTIAL
BMA117159
3
TABLE OF CONTENTS
PAGE
1.
INTRODUCTION......................................................................................................4
1.1.
RAP Amendments ........................................................................................5
2.
SUMMARY OF KEY PROTOCOL INFORMATION ..................................................6
3.
REFERENCES.........................................................................................................7
4.
APPENDICIES.........................................................................................................8
4.1.
Appendix 12: List of Data Displays................................................................8
4.1.1.
Data Display Numbering................................................................8
4.1.2.
Deliverables...................................................................................8
4.1.3.
Study Population Tables................................................................9
4.1.4.
Safety Tables...............................................................................11
4.1.5.
Pharmacokinetic Tables...............................................................15
4.1.6.
Pharmacokinetic Figures .............................................................16
4.1.7.
Pharmacokinetic / Pharmacodynamic (and / or Biomarker) 
Figures ........................................................................................17
4.1.8.
ICH Listings .................................................................................17
4.1.9.
Non-ICH Listings..........................................................................28


CONFIDENTIAL
BMA117159
4
1.
INTRODUCTION
The purpose of this reporting and analysis plan (RAP) is to update the list of displays to 
be included in the End of Study Clinical Study Report for Protocol:
Revision Chronology:
2012N155299_00
2013-DEC-26
Original
2012N155299_01
2014-MAR-01
Amendment No. 1. Country specific Amendment for the 
United Kingdom to address required changes per MHRA.  
Updated Exclusion Criteria to exclude subjects with current 
corneal disease or history of corneal disease.  Updated 
QTc withdrawal criterion to modify QTc withdrawal for QTc 
>500msec and to include > 60 msec increase from 
baseline.  Updated Data Management Section 12 to 
include details on dissemination of data and 
communication plan.  
2012N155299_02
2014-MAR-20
Amendment No. 2. Global Amendment to address required 
changes per the FDA.  Updated Inclusion Criteria with 
minimum weight requirement.  Updated Blood Volumes.  
Revised Time and Events Tables. Corrected typographical 
errors.
2012N155299_03
2014-MAY-05
Amendment No. 3. Country specific Amendment for 
Canada to address required changes per Health Canada.  
Updated preparation instructions of GSK2857916.
2012N155299_04
2016-MAY-05
Amendment No. 4. Global Amendment to include patient 
reported outcome instruments in the Part 2 multiple 
myeloma cohort and refine the lymphoma histologies 
eligible in Part 2 BCMA-expressing lymphoma cohort. 
Additionally, the requirement for 60% of tumor cells 
staining positive for BCMA expression was removed. The 
total number of subjects that may be enrolled is presented 
by a range of 80 to 95 to provide an updated estimate 
based on the number of subjects who enrolled at the time 
of the amendment.  Additional modifications include: 
changing the time-point specific blood specimens are 
collected for baseline/pre-treatment immunogenicity and 
biomarker measurements, and the visit window for certain 
assessments.
2012N155299_05
2017-NOV-02
Global amendment to include additional follow up of 
multiple myeloma subjects for ocular exams (for those 
whose corneal signs or symptoms have not resolved), 
additional patient reported outcome instruments, addition of 
time-to-event endpoints as exploratory objectives. Subjects 
who have completed treatment or the 3 month follow up 
visit (end of study) prior to amendment 5 will be 
reconsented for further follow up and survival status. Other 
administrative changes are also included


CONFIDENTIAL
BMA117159
5
1.1.
RAP Amendments 
Revision chronology: updated the list of displays (Appendix 12 of RAP Amendment 1
for primary analysis) for multiple myeloma and lymphoma subjects to be included in the 
End of Study Clinical Study Report for Protocol. For multiple myeloma subjects, only 
displays with information that may significantly change after primary analysis are 
included. For lymphoma subjects, given the small number of subjects, the majority of the 
displays will be listings. 


CONFIDENTIAL
BMA117159
6
2.
SUMMARY OF KEY PROTOCOL INFORMATION
There are no changes to the planned analyses, analysis method and data handling 
convention as described in RAP amendment 1. The only update is the list of displays for 
end of study analysis.


CONFIDENTIAL
BMA117159
7
3.
REFERENCES
GlaxoSmithKline Document, Reporting and Analysis Plan Amendment 1 for study ID 
BMA117159: Phase I Open-label, Dose Escalation Study to Investigate the Safety, 
Pharmacokinetics, Pharmacodynamics, Immunogenicity and Clinical Activity of the 
Antibody Drug Conjugate GSK2857916 in Subjects with Relapsed/Refractory Multiple 
Myeloma and Other Advanced Hematologic Malignancies Expressing BCMA. Effective 
date as 06-NOV-2018.


CONFIDENTIAL
BMA117159
8
4.
APPENDICIES
4.1.
Appendix 12: List of Data Displays
4.1.1.
Data Display Numbering
The following numbering will be applied for RAP generated displays:
Section
Tables
Figures
Study Population
1.0010 to 1.xxxx
11.0010 to 11.xxxx
Efficacy
2.0010 to 2.xxxx
12.0010 to 12.xxxx
Safety
3.0010 to 3.xxxx
13.0010 to 13.xxxx
Pharmacokinetic
4.0010 to 4.xxxx
14.0010 to 14.xxxx
Population Pharmacokinetic (PopPK)
5.0010 to 5.xxxx
15.0010 to 15.xxxx
Pharmacodynamic and / or Biomarker
6.0010 to 6.xxxx
16.0010 to 16.xxxx
Pharmacokinetic / Pharmacodynamic
7.0010 to 7.xxxx
17.0010 to 17.xxxx
Section
Listings
ICH Listings
1.0010 to 1.xxxx
Other Listings
30.0010 to 30.xxxx
4.1.2.
Deliverables
Delivery [Priority] [1]
Description
DS [X]
During Study
DE [X]
Dose Escalation
IA SAC [X]
Interim Analysis Statistical Analysis Complete
SAC [X]
Final Statistical Analysis Complete
NOTES: 
1.
Indicates priority (i.e. order) in which displays will be generated for the reporting effort.


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9
4.1.3.
Study Population Tables
Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Subject Disposition
1.0010
All Treated
ES8
Summary of Subject Status and Reason for Study Withdrawal 
(Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total). 
EOS SAC
1.0011
All Treated
ES8
Summary of Subject Status and Reason for Study Withdrawal 
(Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). 
EOS SAC
1.0013
All Treated
ES8
Summary of Subject Status and Reason for Study Withdrawal 
(Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
EOS SAC
1.0020
All Treated
SD4
Summary of Treatment Status and Reasons for Discontinuation 
of Study Treatment (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total). Only 
deliver if data change after primary 
analysis SAC
EOS SAC
1.0021
All Treated
SD4
Summary of Treatment Status and Reasons for Discontinuation 
of Study Treatment (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
EOS SAC
1.0023
All Treated
SD4
Summary of Treatment Status and Reasons for Discontinuation 
of Study Treatment (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
EOS SAC
1.0053
All Treated
IE1
Summary of Inclusion/Exclusion Criteria Deviations (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
EOS SAC
Protocol Deviation
1.0043
All Treated
DV1
Summary of Important Protocol Deviations (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL). 
EOS SAC
Demographic and Baseline Characteristics
1.0073
All Treated
DM1
Summary of Demographic Characteristics (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
EOS SAC


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10
Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0291
Enrolled
DM11
Summary of Age Ranges (NHL)
Include columns "No Treatment", 
"Part 2 NHL", "Total"
EOS SAC
1.0083
All Treated
DM5
Summary of Race and Racial Combinations (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
EOS SAC
1.0193
All Treated
MH1
Summary of Past Medical Conditions (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
EOS SAC
1.0203
All Treated
MH1
Summary of Current Medical Conditions (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL). 
EOS SAC
1.0213
All Treated
CM8
Summary of Concomitant Medications (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL). 
EOS SAC
Exposure and Treatment Compliance
1.0243
All Treated
OEX5
Summary of Exposure to GSK2857916 (Part 2 NHL)
Report for population: 3.4 NHL, 
(Summarize: Total)
Do not need "Dose Intensity " 
section. Use 4, <4, >4 cycles
EOS SAC
Duration of Follow-up
1.0310
All Treated
FAC2
Summary of Duration of Follow-up (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total). 
Include all optional columns. 
EOS SAC
1.0311
All Treated
FAC2
Summary of Duration of Follow-up (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Include all optional 
columns. 
EOS SAC
1.0313
All Treated
FAC2
Summary of Duration of Follow-up (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL). 
Include all optional columns. 
EOS SAC


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11
4.1.4.
Safety Tables
Safety: Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Adverse Events (AEs)
3.0030
All Treated
OAE01
Summary of All Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
EOS SAC
3.0031
All Treated
OAE01
Summary of All Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). 
EOS SAC
3.0033
All Treated
OAE01
Summary of All Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) 
EOS SAC
3.0793
All Treated
AE3
Summary of Common (>=5%) Grade 2-4 Adverse Events by 
Overall Frequency (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) 
EOS SAC
3.0060
All Treated
OAE01
Summary of All Drug-Related Adverse Events by System Organ 
Class and Preferred Term and Maximum Grade (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
EOS SAC
3.0061
All Treated
OAE01
Summary of All Drug-Related Adverse Events by System Organ 
Class and Preferred Term and Maximum Grade (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). 
EOS SAC
3.0063
All Treated
OAE01
Summary of All Drug-Related Adverse Events by System Organ 
Class and Preferred Term and Maximum Grade (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) 
EOS SAC
3.0693
All Treated
AE15
Summary of Common (>=5%) Non-serious Adverse Events by 
System Organ Class and Preferred Term (Number of 
Participants and Occurrences) (Part 2 NHL)
Report for: Part 2 NHL, (Summarize 
for Total). Include baseline values.
EOS SAC
3.0713
All Treated
AE3
Summary of Common (>=5%) Drug-Related Grade 2-4 Adverse 
Events by Overall Frequency (Part 2 NHL)
Report for: Part 2 NHL, (Summarize 
for Total). Include baseline values. 
EOS SAC
3.0700
All Treated
AE16
Summary of Serious Adverse Events by System Organ Class 
and Preferred Term (Number of Participants and Occurrences) 
(Part 1)
Report for: Part 1, (Summarize by 
ascending dose level, Total). 
EOS SAC


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BMA117159
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Safety: Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0701
All Treated
AE16
Summary of Serious Adverse Events by System Organ Class 
and Preferred Term (Number of Participants and Occurrences) 
(Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). 
EOS SAC
3.0703
All Treated
AE16
Summary of Serious Adverse Events by System Organ Class 
and Preferred Term (Number of Participants and Occurrences) 
(Part 2 NHL)
Report for: Part 2 NHL, (Summarize 
for Total). 
EOS SAC
3.0131
All Treated
AE1
Summary of Adverse Events Leading to Dose Reduction by 
System Organ Class and Preferred Term (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
EOS SAC
3.0133
All Treated
AE1
Summary of Adverse Events Leading to Dose Reduction by 
System Organ Class and Preferred Term (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
EOS SAC
3.0141
All Treated
AE1
Summary of Adverse Events Leading to Dose Interruptions or 
Delays by System Organ Class and Preferred Term (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
EOS SAC
3.0143
All Treated
AE1
Summary of Adverse Events Leading to Dose Interruptions or 
Delays by System Organ Class and Preferred Term (Part 2 
NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
EOS SAC
3.0273
All Treated
LB1
Summary of Chemistry Changes from Baseline (Part 2 NHL)
Report for: Part 2 NHL, (Summarize 
for Total). Include baseline values. 
EOS SAC
3.0283
All Treated
OLB11B
Summary of Chemistry Changes from Baseline with Respect to 
the Normal Range (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) 
Include only 'worst-case post-
baseline' 
EOS SAC
3.0293
All Treated
OLB9B
Summary of Chemistry Grade Changes from Baseline Grade 
(Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: Total). Produce only 
for lab tests that are graded. For 
laboratory tests that are graded for 
both low and high values, 
EOS SAC


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BMA117159
13
Safety: Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
summaries will be done separately 
and labeled by direction. Include 
only 'worst-case post-baseline' 
3.0303
All Treated
LB1
Summary of Hematology Changes from Baseline (Part 2 NHL)
Report for: Part 2 NHL, (Summarize 
for Total). Include baseline values. 
EOS SAC
3.0313
All Treated
OLB11B
Summary of Hematology Changes from Baseline with Respect 
to the Normal Range (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) 
Include only 'worst-case post-
baseline' 
EOS SAC
3.0323
All Treated
OLB9B
Summary of Hematology Grade Changes from Baseline Grade 
(Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: Total). Produce only 
for lab tests that are graded. For 
laboratory tests that are graded for 
both low and high values, 
summaries will be done separately 
and labeled by direction. Include 
only 'worst-case post-baseline' 
EOS SAC
ECG
3.0223
All Treated
VS1
Summary of Change from Baseline in Vital Signs (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) Add 
Cycle, Visit. Include baseline 
values. 
EOS SAC
3.0373
All Treated
EG1
Summary of ECG Findings (Part 2 NHL)
Report for: All Treated MM, 
(Summarize for Total). Include 
baseline values.
EOS SAC
3.0393
All Treated
OECG1B
Summary of Worst-case Increases in Fridericia's QTc (Part 2 
Report for: Part 2 NHL, 
EOS SAC


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BMA117159
14
Safety: Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
NHL)
(Summarize: Total). Include only 
'worst-case post-baseline'
3.0403
All Treated
OECG2B
Summary of Worst-case Amount of Increase from Baseline 
Value in Fridericia's QTc (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: Total). Include only 
'worst-case post-baseline'
EOS SAC
Death
3.0570
All Treated
DTH1a
Summary of Deaths (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
EOS SAC
3.0571
All Treated
DTH1a
Summary of Deaths (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). 
EOS SAC
3.0573
All Treated
DTH1a
Summary of Deaths (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) 
EOS SAC
Anti-Drug Antibody
3.0843
All Treated
SAFE_T
4
Summary of Human Anti-GSK2857916 Antibodies (ADA) Over 
Time (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) 
EOS SAC
3.0853
All Treated
SAFE_T
5
Summary of Anti-GSK2857916 Antibodies (ADA) (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) 
EOS SAC


CONFIDENTIAL
BMA117159
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4.1.5.
Pharmacokinetic Tables
Pharmacokinetic: Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Concentration
4.0013
PK
PK01
Summary of Plasma GSK2857916 (ADC) PK Concentration-
Time Data (Part 2 NHL)
EOS SAC
4.0023
PK
PK01
Summary of Plasma GSK2857916 (Total Antibody) PK 
Concentration-Time Data (Part 2 NHL)
EOS SAC
4.0043
PK
PK01
Summary of Plasma cys-mcMMAF PK Concentration-Time 
Data (Part 2 NHL)
EOS SAC


CONFIDENTIAL
BMA117159
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4.1.6.
Pharmacokinetic Figures
Pharmacokinetic: Figures
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Concentration
14.0013
PK
PK16
Individual Plasma GSK2857916 (ADC) Concentration-Time 
Plots (Linear and Semi-Log) (Part 2 NHL)
EOS SAC
14.0023
PK
PK16
Individual Plasma GSK2857916 (Total Antibody) 
Concentration-Time Plots (Linear and Semi-Log) (Part 2 NHL)
EOS SAC
14.0043
PK
PK16
Individual Plasma cys-mcMMAF Concentration-Time Plots 
(Linear and Semi-Log) (Part 2 NHL)
EOS SAC
14.0053
PK
PK17
Mean Plasma GSK2857916 (ADC) Concentration-Time Plots 
(Linear and Semi-Log) (Part 2 NHL)
EOS SAC
14.0063
PK
PK17
Mean Plasma GSK2857916 (Total Anti-body) Concentration-
Time Plots (Linear and Semi-Log) (Part NHL)
EOS SAC
14.0083
PK
PK17
Mean Plasma GSK2857916 (cys-mcMMAF) Concentration-
Time Plots (Linear and Semi-Log) (Part 2 NHL)
EOS SAC
14.0093
PK
PK18
Median Plasma GSK2857916 (ADC) Concentration-Time 
Plots (Linear and Semi-Log) (Part 2 NHL)
EOS SAC
14.0103
PK
PK18
Median Plasma GSK2857916 (Total Anti-body) 
Concentration-Time Plots (Linear and Semi-Log) (Part 2 NHL)
EOS SAC
14.0123
PK
PK18
Median Plasma GSK2857916 (cys-mcMMAF) Concentration-
Time Plots (Linear and Semi-Log) (Part 2 NHL)
EOS SAC


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17
4.1.7.
Pharmacokinetic / Pharmacodynamic (and / or Biomarker) Figures
Pharmacokinetic / Pharmacodynamic: Figures
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
16.0014
PK/PD
PK_F2
Plot of Fridericia’s QTc Change from Baseline versus PK 
Concentration for GSK2857916 (ADC) (All Treated)
disease type color-coded
EOS SAC
16.0024
PK/PD
PK_F2
Plot of Fridericia’s QTc Change from Baseline versus PK 
Concentration for GSK2857916 (Total Antibody) (All Treated)
disease type color-coded
EOS SAC
16.0044
PK/PD
PK_F2
Plot of Fridericia’s QTc Change from Baseline versus PK 
Concentration for cys-mcMMAF (All Treated)
disease type color-coded
EOS SAC
4.1.8.
ICH Listings
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Subject Disposition
1.0010
All Treated
ES2
Listing of Reasons for Study Withdrawal (All Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
1.0011
All Treated
ES2
Listing of Reasons for Study Withdrawal (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
1.0021
All Treated
CP_RA1p
Listing of Planned and Actual Treatments (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
1.0030
All Treated
SD2
Listing of Reasons for Study Treatment Discontinuation (All 
Report for sub-population: All 
EOS SAC


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18
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Treated MM)
Treated MM.
1.0031
All Treated
SD2
Listing of Reasons for Study Treatment Discontinuation (Part 2 
NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
Protocol Deviations
1.0040
All Treated
DV2
Listing of Important Protocol Deviations (All Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
1.0041
All Treated
DV2
Listing of Important Protocol Deviations (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
1.0050
All Treated
IE3
Listing of Subjects with Inclusion/Exclusion Criteria Deviations 
(All Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
1.0051
All Treated
IE3
Listing of Subjects with Inclusion/Exclusion Criteria Deviations 
(Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
Populations Analysed
1.0061
All Treated
SA3a
Listing of Subjects Excluded from Any Population (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
Demographic and Baseline Characteristics
1.0071
All Treated
DM2
Listing of Demographic Characteristics (Part 2 NHL)
Report for sub-population: Part 2 
NHL. Add BMI (kg/m2).
EOS SAC
1.0081
All Treated
DM9
Listing of Race (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC


CONFIDENTIAL
BMA117159
19
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Prior and Concomitant Medications
1.0620
All Treated
OCM1A
Listing of Concomitant Medications (All Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
1.0621
All Treated
OCM1A
Listing of Concomitant Medications (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
Exposure and Treatment Compliance
1.0090
All Treated
OEX8A
Listing of Exposure Data (All Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
1.0091
All Treated
OEX8A
Listing of Exposure Data (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
1.0100
All Treated
ODMOD10A
Listing of Dose Reductions (All Treated MM)
Report for sub-population: All 
Treated MM. Include Planned 
Time. 
EOS SAC
1.0101
All Treated
ODMOD10A
Listing of Dose Reductions (Part 2 NHL)
Report for sub-population: All 
Treated MM. Include Planned 
Time. 
EOS SAC
1.0110
All Treated
ODMOD12A
Listing of Dose Delays (All Treated MM)
Report for sub-population: All 
Treated MM. Include Planned 
Time. IDSL standard does not 
report demographic info.  
 to check with
 
 regarding planned time and 
cycle day. If it is too much 
programming work to change now, 
we can keep it as it is.
EOS SAC
PPD
PPD
PPD


CONFIDENTIAL
BMA117159
20
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0111
All Treated
ODMOD12A
Listing of Dose Delays (Part 2 NHL)
Report for sub-population: All 
Treated MM. Include Planned 
Time. IDSL standard does not 
report demographic info.  
 to check with 
 regarding planned time and 
cycle day. If it is too much 
programming work to change now, 
we can keep it as it is.
EOS SAC
1.0120
All Treated
ODMOD15A
Listing of Dose Escalations (All Treated MM)
Report for sub-population: All 
Treated MM. Include 
Age(y)/Sex/Race, Cycle, Visit.
For C2MD, list the dose 
escalations where a dose 
escalation is indicated in the data –
from the site.
EOS SAC
1.0121
All Treated
ODMOD15A
Listing of Dose Escalations (Part 2 NHL)
Report for sub-population: All 
Treated MM. Include 
Age(y)/Sex/Race, Cycle, Visit.
For C2MD, list the dose 
escalations where a dose 
escalation is indicated in the data –
from the site.
EOS SAC
1.0490
All Treated
ODMOD14A
Listing of Incomplete Infusions (All Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
1.0491
All Treated
ODMOD14A
Listing of Incomplete Infusions (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
PPD
PPD
PPD


CONFIDENTIAL
BMA117159
21
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0500
All Treated
ODMOD17A
Listing of Infusion Interruptions (All Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
1.0501
All Treated
ODMOD17A
Listing of Infusion Interruptions (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
Adverse Events
1.0140
All Treated
OAE04
Listing of All Adverse Events (All Treated MM)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
EOS SAC
1.0141
All Treated
OAE04
Listing of All Adverse Events (Part 2 NHL)
Report for population subgroup: 
Part 2 NHL. Remove onset cycle 
and cycle day from all AE related 
listings.
EOS SAC
1.0150
All Treated
OAE03
Listing of Subject Numbers for Individual Adverse Events (All 
Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
1.0151
All Treated
OAE03
Listing of Subject Numbers for Individual Adverse Events (Part 
2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
1.0160
All Treated
AE2
Listing of Relationship Between Adverse Event System Organ 
Classes, Preferred Terms, and Verbatim Text (All Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
1.0161
All Treated
AE2
Listing of Relationship Between Adverse Event System Organ 
Classes, Preferred Terms, and Verbatim Text (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC


CONFIDENTIAL
BMA117159
22
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Serious and Other Significant Adverse Events
1.0180
All Treated
OAE04
Listing of Fatal Serious Adverse Events (All Treated MM)
Report for sub-population: All 
Treated MM. Include column to 
indicate relationship to study 
treatment.
EOS SAC
1.0181
All Treated
OAE04
Listing of Fatal Serious Adverse Events (Part 2 NHL)
Report for sub-population: All 
Treated MM. Include column to 
indicate relationship to study 
treatment.
EOS SAC
1.0190
All Treated
OAE04
Listing of Non-Fatal Serious Adverse Events (All Treated MM)
Report for sub-population: All 
Treated MM. Include column to 
indicate relationship to study 
treatment.
EOS SAC
1.0191
All Treated
OAE04
Listing of Non-Fatal Serious Adverse Events (Part 2 NHL)
Report for sub-population: All 
Treated MM. Include column to 
indicate relationship to study 
treatment.
EOS SAC
1.0460
All Treated
AE14
Listing of Reasons for Considering as a Serious Adverse Event 
(All Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
1.0461
All Treated
AE14
Listing of Reasons for Considering as a Serious Adverse Event 
(Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
1.0470
All Treated
OAE04
Listing of Adverse Events Leading to Withdrawal from Study / 
Permanent Discontinuation of Study Treatment (All Treated 
MM)
Report for sub-population: All 
Treated MM.
EOS SAC
1.0471
All Treated
OAE04
Listing of Adverse Events Leading to Withdrawal from Study / 
Permanent Discontinuation of Study Treatment (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC


CONFIDENTIAL
BMA117159
23
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0200
All Treated
OAE04
Listing of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment (All Treated MM)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
EOS SAC
1.0201
All Treated
OAE04
Listing of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment (Part 2 NHL)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
EOS SAC
1.0240
All Treated
OAE04
Listing of Adverse Events Leading to Dose Reduction (All 
Treated MM)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
EOS SAC
1.0241
All Treated
OAE04
Listing of Adverse Events Leading to Dose Reduction (Part 2 
NHL)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
EOS SAC
1.0250
All Treated
OAE04
Listing of Adverse Events Leading to Dose Interruptions or 
Delays (All Treated MM)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
EOS SAC
1.0251
All Treated
OAE04
Listing of Adverse Events Leading to Dose Interruptions or 
Delays (Part 2 NHL)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
EOS SAC
1.0510
All Treated
OAE04
Listing of Adverse Events Leading to Incomplete Infusions (All 
Treated MM)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
EOS SAC


CONFIDENTIAL
BMA117159
24
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
listings.
1.0511
All Treated
OAE04
Listing of Adverse Events Leading to Incomplete Infusions (Part 
2 NHL)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
EOS SAC
1.0520
All Treated
OAE04
Listing of Adverse Events Leading to Infusion Interruptions (All 
Treated MM)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
EOS SAC
1.0521
All Treated
OAE04
Listing of Adverse Events Leading to Infusion Interruptions 
(Part 2 NHL)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
EOS SAC
1.0270
All Treated
OAE04
Listing of Corneal Events (All Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
1.0271
All Treated
OAE04
Listing of Corneal Events (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
1.0530
All Treated
OAE04
Listing of Thrombocytopenia (All Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
1.0531
All Treated
OAE04
Listing of Thrombocytopenia (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
1.0540
All Treated
OAE04
Listing of Hematologic Toxicity (All Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
1.0541
All Treated
OAE04
Listing of Hematologic Toxicity (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC


CONFIDENTIAL
BMA117159
25
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0550
All Treated
OAE04
Listing of Neutropenia (All Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
1.0551
All Treated
OAE04
Listing of Neutropenia (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
1.0260
All Treated
OAE04
Listing of Infusion Related Reactions (All Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
1.0261
All Treated
OAE04
Listing of Infusion Related Reactions (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
Hepatobiliary (Liver)
1.0410
All Treated
MH2
Listing of Medical Conditions for Subjects with Liver Stopping 
Events (All Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
1.0411
All Treated
MH2
Listing of Medical Conditions for Subjects with Liver Stopping 
Events (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
1.0420
All Treated
SU2
Listing of Substance Use for Subjects with Liver Stopping 
Events (All Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
1.0421
All Treated
SU2
Listing of Substance Use for Subjects with Liver Stopping 
Events (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC


CONFIDENTIAL
BMA117159
26
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
All Laboratory
1.0330
All Treated
OLB7
Listing of All Laboratory Data for Subjects with Any Value of 
Potential Clinical Importance (All Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
1.0331
All Treated
OLB7
Listing of All Laboratory Data for Subjects with Any Value of 
Potential Clinical Importance (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
1.0320
All Treated
OLB13
Listing of Laboratory Data with Character Results (All Treated 
MM)
Report for sub-population: All 
Treated MM.
EOS SAC
1.0321
All Treated
OLB13
Listing of Laboratory Data with Character Results (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
1.0350
All Treated
UR2A
Listing of Urinalysis Data for Subjects with Any Value of 
Potential Clinical Importance (All Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
1.0351
All Treated
UR2A
Listing of Urinalysis Data for Subjects with Any Value of 
Potential Clinical Importance (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
ECOG Performance Status
1.0430
All Treated
PS5A
Listing of ECOG Performance Status (All Treated MM)
Report for sub-population: Part 2 
NHL.
EOS SAC
1.0431
All Treated
PS5A
Listing of ECOG Performance Status (Part 2 NHL)
Report for sub-population: All 
Treated MM.
EOS SAC
Response
1.0560
All Treated
RE5
Listing of Investigator-Assessed Responses (All Treated MM)
Report for sub-population: All 
Treated MM. List investigator 
reported response by visit.
EOS SAC
1.0561
All Treated
RE5
Listing of Investigator-Assessed Responses (Part 2 NHL)
Report for sub-population: Part 2 
NHL. List investigator reported 
EOS SAC


CONFIDENTIAL
BMA117159
27
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
response by visit.
Death
1.0390
All Treated
DTH3
Listing of Deaths (All Treated MM)
Report for sub-population: All 
Treated MM. include the time from 
last dose in the listing and Number 
of Cycles/Last Dose (optional 
columns in DTH3). 
EOS SAC
1.0391
All Treated
DTH3
Listing of Deaths (Part 2 NHL)
Report for sub-population: Part 2 
NHL. include the time from last 
dose in the listing and Number of 
Cycles/Last Dose (optional 
columns in DTH3).
EOS SAC
PK
1.0631
PK
PK07
Listing of Plasma GSK2857916 (ADC) Pharmacokinetic 
Concentration-Time Data (NHL)
EOS SAC
1.0641
PK
PK07
Listing of Plasma GSK2857916 (Total Antibody) 
Pharmacokinetic Concentration-Time Data (NHL)
EOS SAC
1.0661
PK
PK07
Listing of Plasma cys-mcMMAF Pharmacokinetic 
Concentration-Time Data (NHL)
EOS SAC


CONFIDENTIAL
BMA117159
28
4.1.9.
Non-ICH Listings
Non-ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Medical Conditions
30.0011
All Treated
MH2
Listing of Past Cancer-Related and Non-Cancer Related 
Medical Conditions (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
30.0021
All Treated
MH2
Listing of Current Cancer-Related and Non-Cancer Related 
Medical Conditions (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
Concomitant Medications
30.0310
All Treated
OCM1A
Listing of Prophylactic Medication for Infusion-Related 
Reactions (All Treated MM)
Report for sub-population: All 
Treated MM. Please replace the 
2nd column as ‘Drug Class/Drug 
Name’ and the last column as 
‘Reason for Medication’ 
EOS SAC
30.0311
All Treated
OCM1A
Listing of Prophylactic Medication for Infusion-Related 
Reactions (Part 2 NHL)
Report for sub-population: Part 2 
NHL. Please replace the 2nd 
column as ‘Drug Class/Drug 
Name’ and the last column as 
‘Reason for Medication’ 
EOS SAC
30.0320
All Treated
OCM1A
Listing of Eye Medications (All Treated MM)
Report for sub-population: All 
Treated MM. Please replace the 
2nd column as ‘Drug Class/Drug 
Name’ and the last column as 
‘Reason for Medication’
EOS SAC
30.0321
All Treated
OCM1A
Listing of Eye Medications (Part 2 NHL)
Report for sub-population: Part 2 
NHL. Please replace the 2nd 
column as ‘Drug Class/Drug 
EOS SAC


CONFIDENTIAL
BMA117159
29
Non-ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Name’ and the last column as 
‘Reason for Medication’
Blood and Blood Supportive Care Products
30.0380
All Treated
BP4
Listing of Blood Products (All Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
30.0381
All Treated
BP4
Listing of Blood Products (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
30.0390
All Treated
BP5
Listing of Blood Supportive Care Products (All Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
30.0391
All Treated
BP5
Listing of Blood Supportive Care Products (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
Substance Use
30.0370
All Treated
SU2
Listing of Substance Use (All Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
30.0371
All Treated
SU2
Listing of Substance Use (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
Anti-Cancer Therapy, Radiotherapy and Surgical Procedures
30.0041
All Treated
AC6
Listing of Prior Anti-Cancer Therapy (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
30.0050
All Treated
AC7
Listing of Anti-Cancer Radiotherapy (All Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
30.0051
All Treated
AC7
Listing of Anti-Cancer Radiotherapy (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
30.0060
All Treated
OSP3
Listing of Prior/On Treatment Cancer and Non-Cancer 
Report for sub-population: All 
EOS SAC


CONFIDENTIAL
BMA117159
30
Non-ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Related Surgical Procedures (All Treated MM)
Treated MM.
30.0061
All Treated
OSP3
Listing of Prior/On Treatment Cancer and Non-Cancer 
Related Surgical Procedures (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
30.0400
All Treated
FAC3
Listing of Follow-Up Anti-Cancer Therapy (All Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
30.0401
All Treated
FAC3
Listing of Follow-Up Anti-Cancer Therapy (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
Disease Characteristics
30.0081
All Treated
DC4
Listing of Disease Characteristics at Screening (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
30.0361
All Treated
DC3
Listing of Disease Characteristics at Initial Diagnosis (Part 2 
NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
Exposure
30.0130
All Treated
OEX9
Summary Listing of Overall Exposure and Dose Modifications 
(All Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
30.0131
All Treated
OEX9
Summary Listing of Overall Exposure and Dose Modifications 
(Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
Adverse Events
30.0540
All Treated
OAE4
Listing of Serious Adverse Events (All Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
30.0541
All Treated
OAE4
Listing of Serious Adverse Events (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
30.0550
All Treated
OAE04
Listing of Drug-Related Adverse Events (All Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC


CONFIDENTIAL
BMA117159
31
Non-ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
30.0551
All Treated
OAE04
Listing of Drug-Related Adverse Events (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
30.0560
All Treated
OAE4
Listing of Drug-Related Serious Adverse Events (All Treated 
MM)
Report for sub-population: All 
Treated MM.
EOS SAC
30.0561
All Treated
OAE4
Listing of Drug-Related Serious Adverse Events (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
30.0450
All Treated
AE2
Listing of Relationship Between SOC and Verbatim Text for 
AEs Collapsed to Corneal Events 
EOS SAC
30.0460
All Treated
AE2
Listing of Relationship Between SOC and Verbatim Text for 
AEs Collapsed to Thrombocytopenia 
EOS SAC
30.0470
All Treated
AE2
Listing of Relationship Between SOC and Verbatim Text for 
AEs Collapsed to Neutrupenia 
EOS SAC
30.0480
All Treated
AE2
Listing of Relationship Between SOC and Verbatim Text for 
AEs Collapsed to Hematologic Toxicity 
EOS SAC
30.0490
All Treated
AE2
Listing of Relationship Between SOC and Verbatim Text for 
AEs Collapsed to Infusion related reactions 
EOS SAC
Deaths
30.0570
All Treated
DTH5
Listing of Subject Numbers for Specific Causes of Deaths (All 
Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
30.0571
All Treated
DTH5
Listing of Subject Numbers for Specific Causes of Deaths 
(Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
Laboratory
30.0530
All Treated
OLB7
Listing of Grade 3 and Grade 4 Laboratory Data (All Treated 
MM)
Report for sub-population: All 
Treated MM.
EOS SAC


CONFIDENTIAL
BMA117159
32
Non-ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
30.0531
All Treated
OLB7
Listing of Grade 3 and Grade 4 Laboratory Data (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
30.0580
All Treated
LIVER13
Listing of Subjects Meeting Hepatobiliary Laboratory Criteria 
Post-Baseline (All Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
30.0581
All Treated
LIVER13
Listing of Subjects Meeting Hepatobiliary Laboratory Criteria 
Post-Baseline (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
30.0160
All Treated
LIVER5
Listing of Liver Monitoring/Stopping Event Reporting (All 
Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
30.0161
All Treated
LIVER5
Listing of Liver Monitoring/Stopping Event Reporting (Part 2 
NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
Constitutional Symptoms and Organ Examinations
30.0510
All Treated
OCS3
Listing of Constitutional Symptoms (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
30.0520
All Treated
OOE2
Listing of Organ Examinations (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
Left Ventricular Ejection Fraction
30.0500
All Treated
OLVEF2A
Listing of Left Ventricular Ejection Fraction Results (All 
Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
30.0501
All Treated
OLVEF2A
Listing of Left Ventricular Ejection Fraction Results (Part 2 
NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
ECG
30.0140
All Treated
OECG5A
Listing of Fridericia’s QTc Values of Potential Clinical 
Importance (All Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
30.0141
All Treated
OECG5A
Listing of Fridericia’s QTc Values of Potential Clinical 
Report for sub-population: Part 2 
EOS SAC


CONFIDENTIAL
BMA117159
33
Non-ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Importance (Part 2 NHL)
NHL.
Vital Signs
30.0440
All Treated
OVT7A
Listing of Vital Sign Values of Potential Clinical Importance
(All Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
30.0441
All Treated
OVT7A
Listing of Vital Sign Values of Potential Clinical Importance 
(Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
Ocular Exam
30.0260
All Treated
SAFE_L2
Listing of Visual Acuity and Abnormal Corneal Exam Results 
(All Treated MM)
Report for sub-population: All 
Treated MM.
EOS SAC
30.0261
All Treated
SAFE_L2
Listing of Visual Acuity and Abnormal Corneal Exam Results 
(Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC
30.0330
All Treated
SAFE_L2
Listing of Abnormal Conjunctival Exam Results (All Treated 
MM)
Report for sub-population: All 
Treated MM. Please include 
screening results and any post-
baseline abnormal results for 
each patient. Include: Centre ID/
Subj., Age(y)/ Sex/ Race, 
Reported Corneal Events (Y/N), 
Cycle/Visit, Time Since 1st 
Dose/ Time Since last Dose, 
Eye, Exam Test, Result
EOS SAC
30.0331
All Treated
SAFE_L2
Listing of Abnormal Conjunctival Exam Results (Part 2 NHL)
Report for sub-population: Part 2 
NHL. Please include screening 
results and any post-baseline 
abnormal results for each 
patient. Include: Centre ID/
EOS SAC


CONFIDENTIAL
BMA117159
34
Non-ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Subj., Age(y)/ Sex/ Race, 
Reported Corneal Events (Y/N), 
Cycle/Visit, Time Since 1st 
Dose/ Time Since last Dose, 
Eye, Exam Test, Result
30.0340
All Treated
SAFE_L2
Listing of Abnormal Slit Lamp Anterior Chamber and Slit 
Lamp Lens Exam Results (All Treated MM)
Report for sub-population: All 
Treated MM. Please include 
screening results and any post-
baseline abnormal results for 
each patient. Include: Centre ID/
Subj., Age(y)/ Sex/ Race, 
Reported Corneal Events (Y/N), 
Cycle/Visit, Time Since 1st 
Dose/ Time Since last Dose, 
Eye, Exam Test, Result
EOS SAC
30.0341
All Treated
SAFE_L2
Listing of Abnormal Slit Lamp Anterior Chamber and Slit 
Lamp Lens Exam Results (Part 2 NHL)
Report for sub-population: Part 2 
NHL. Please include screening 
results and any post-baseline 
abnormal results for each 
patient. Include: Centre ID/
Subj., Age(y)/ Sex/ Race, 
Reported Corneal Events (Y/N), 
Cycle/Visit, Time Since 1st 
Dose/ Time Since last Dose, 
Eye, Exam Test, Result
EOS SAC
30.0350
All Treated
SAFE_L2
Listing of Indirect Fundoscopic Exam and Intraocular 
Pressure Results (All Treated MM)
Report for sub-population: All 
Treated MM. Include: Centre ID/
Subj., Age(y)/ Sex/ Race, 
EOS SAC


CONFIDENTIAL
BMA117159
35
Non-ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Reported Corneal Events (Y/N), 
Cycle/Visit, Time Since 1st 
Dose/ Time Since last Dose, 
Eye, Exam Test, Result
30.0351
All Treated
SAFE_L2
Listing of Indirect Fundoscopic Exam and Intraocular 
Pressure Results (Part 2 NHL)
Report for sub-population: Part 2 
NHL. Include: Centre ID/ Subj., 
Age(y)/ Sex/ Race, Reported 
Corneal Events (Y/N), 
Cycle/Visit, Time Since 1st 
Dose/ Time Since last Dose, 
Eye, Exam Test, Result
EOS SAC
30.0810
All Treated
SAFE_L2
Listing of Visual Acuity and Abnormal Corneal Exam Results 
for Subjects with Ocular Exam Results in Follow-up (All 
Treated MM)
EOS SAC
30.0811
All Treated
SAFE_L2
Listing of Visual Acuity and Abnormal Corneal Exam Results 
for Subjects with Ocular Exam Results in Follow-up (Part 2 
NHL)
EOS SAC
Health Outcomes
30.0590
All Treated
VS4
Listing of Symptom Impact and HRQoL Item Scores (All 
Treated MM)
Report for sub-population: All 
Treated MM. Use the format of 
VS4, use collected visit dates. 
List scores for Bone Pain Worst, 
Bone Pain Average, Fatigue
EOS SAC
30.0591
All Treated
VS4
Listing of Symptom Impact and HRQoL Item Scores (Part 2 
NHL)
Report for sub-population: Part 2 
NHL. Use the format of VS4, use 
collected visit dates. List scores 
for Bone Pain Worst, Bone Pain 
EOS SAC


CONFIDENTIAL
BMA117159
36
Non-ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Average, Fatigue
30.0600
All Treated
VS4
Listing of NEI-VFQ-25 Scores (All Treated MM)
Report for sub-population: All 
Treated MM. Use the format of 
VS4, use collected visit dates. 
List overall composite score and 
11 sub-scores.
EOS SAC
30.0601
All Treated
VS4
Listing of NEI-VFQ-25 Scores (Part 2 NHL)
Report for sub-population: Part 2 
NHL. Use the format of VS4, use 
collected visit dates. List overall 
composite score and 11 sub-
scores.
EOS SAC
30.0610
All Treated
VS4
Listing of OSDI Scores (All Treated MM)
Report for sub-population: All 
Treated MM. Use the format of 
VS4, use collected visit dates. 
List total score and 3 sub-
scores.
EOS SAC
30.0611
All Treated
VS4
Listing of OSDI Scores (Part 2 NHL)
Report for sub-population: Part 2 
NHL. Use the format of VS4, use 
collected visit dates. List total 
score and 3 sub-scores.
EOS SAC
Anti-Drug Antibody
30.0620
All Treated
SAFE_L3
Listing of Anti-GSK2857916 antibody results (All Treated 
MM)
Report for sub-population: All 
Treated MM.
EOS SAC
30.0621
All Treated
SAFE_L3
Listing of Anti-GSK2857916 antibody results (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
EOS SAC


CONFIDENTIAL
BMA117159
37
Non-ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
PKPD
30.0691
PKPD
Listing of Fridericia’s QTc Change from Baseline and 
GSK2857916 (ADC) Pharmacokinetic Concentration-Time 
Data (NHL)
List QTc change from baseline 
concentration for each visit
EOS SAC
30.0701
PKPD
Listing of Fridericia’s QTc Change from Baseline and 
GSK2857916 (Total Antibody) Pharmacokinetic 
Concentration-Time Data (NHL)
List QTc change from baseline 
concentration for each visit
EOS SAC
30.0721
PKPD
Listing of Fridericia’s QTc Change from Baseline and cys-
mcMMAF Pharmacokinetic Concentration-Time Data (NHL)
List QTc change from baseline 
concentration for each visit
EOS SAC


CONFIDENTIAL
The GlaxoSmithKline group of companies
BMA117159
1
Division
:
Worldwide Development
Information Type
:
Reporting and Analysis Plan (RAP)
Title
:
DREAMM-1: A Phase I Open-label, Dose Escalation Study 
to Investigate the Safety, Pharmacokinetics, 
Pharmacodynamics, Immunogenicity and Clinical Activity of 
the Antibody Drug Conjugate GSK2857916 in Subjects with 
Relapsed/Refractory Multiple Myeloma and Other Advanced 
Hematologic Malignancies Expressing BCMA
Compound Number 
:
GSK2857916
Effective Date 
:
06-NOV-2018
Description:

The purpose of this RAP is to describe the planned analyses and output to be 
included in the Clinical Study Report for Protocol GSK Document Number 
2012N155299_05.

This RAP is intended to describe the safety, clinical activity and pharmacokinetic
analyses required for the study. 

This RAP will be provided to the study team members to convey the content of the 
Statistical Analysis Complete (SAC) deliverable.
RAP Author(s):
Approver
Date
Approval Method
06-NOV-2018
E-mail
Principal Statistician (Oncology, Clinical 
Statistics)
05-NOV-2018
E-mail
Director (Clinical Pharmacology Modelling & 
Simulation)
Copyright 2018 the GlaxoSmithKline group of companies. All rights reserved.  
Unauthorised copying or use of this information is prohibited.
PPD
PPD


CONFIDENTIAL
BMA117159
2
RAP Team Approvals:
Approver
Date
Approval Method
 (PPL and Medical Monitor)
05-NOV-2018
E-mail
Director Clinical Development (Oncology, ES 
Clinical)
 (CRL)
05-NOV-2018
E-mail
Clinical Development Director (Oncology, 
CPSSO)
(CIL)
05-NOV-2018
E-mail
Clinical Development Director (Oncology, 
Therapy Area Delivery CPSSO Management)
(OSL)
05-NOV-2018
E-mail
Clinical Development Manager (Oncology, 
Therapy Area Delivery CPSSO Management)
 (Global Regulatory Lead)
05-NOV-2018
E-mail
Senior Director (Oncology Therapeutic Group, 
Global Regulatory Affairs)
 (SDL)
05-NOV-2018
E-mail
Safety Development Leader (Pharmacovigilance, 
GCSP)
05-NOV-2018
E-mail
SERM Director (Pharmacovigilance, GCSP)
06-NOV-2018
E-mail
VEO Director (Oncology Value Evidence and 
Outcomes, Value Evidence & Outcomes)
 
05-NOV-2018
E-mail
Director (Patient Centered Outcomes)
05-NOV-2018
E-mail
Director, Statistics (Oncology, Clinical Statistics)
06-NOV-2018
E-mail
Manager Data Management (Oncology, CPSSO 
Data Management)
05-NOV-2018
E-mail
Programming Manager (Oncology, Clinical 
Programming)
06-NOV-2018
E-mail
Head of Medical Writing (Oncology, ES 
Clinical)
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


CONFIDENTIAL
BMA117159
3
Approver
Date
Approval Method
05-NOV-2018
E-mail
Scientific Leader (Immunogenicity and Clinical 
Immunology, In vitro / In vivo Translation)
Clinical Statistics and Clinical Programming Line Approvals:
Approver
Date
Approval Method
05-NOV-2018
E-mail
Senior Statistics Director (Oncology, Clinical 
Statistics)
05-NOV-2018
E-mail
Director Programming (Oncology, Clinical 
Programming)
PPD
PPD
PPD


CONFIDENTIAL
BMA117159
4
TABLE OF CONTENTS
PAGE
1.
INTRODUCTION......................................................................................................8
1.1.
RAP Amendments ........................................................................................9
2.
SUMMARY OF KEY PROTOCOL INFORMATION ................................................10
2.1.
Changes to the Protocol Defined Statistical Analysis Plan..........................10
2.2.
Study Objective(s) and Endpoint(s).............................................................12
2.3.
Study Design ..............................................................................................14
2.4.
Statistical Hypotheses / Statistical Analyses ...............................................15
3.
PLANNED ANALYSES ..........................................................................................16
3.1.
Interim Analyses .........................................................................................16
3.1.1.
Part 1: Dose Escalation Phase ....................................................16
3.1.1.1.
Description of the New Continual 
Reassessment Method...............................................16
3.1.1.2.
Prior Probability Distribution .......................................17
3.1.1.3.
Displays To Be Created For Dose Escalation 
Review .......................................................................18
3.1.2.
Part 2 Expansion Phase ..............................................................18
3.1.2.1.
Multiple Myeloma Expansion Cohort ..........................18
3.1.2.1.1.
Operating Characteristics of the 
Stopping Rules for Futility.......................19
3.1.2.2.
Lymphoma Expansion Cohort ....................................20
3.2.
Administrative Interim Analyses ..................................................................20
3.3.
Final Analyses ............................................................................................20
4.
ANALYSIS POPULATIONS ...................................................................................21
4.1.
Protocol Deviations.....................................................................................22
5.
CONSIDERATIONS FOR DATA ANALYSES AND DATA HANDLING 
CONVENTIONS.....................................................................................................23
5.1.
Study Treatment & Sub-group Display Descriptors.....................................23
5.2.
Baseline Definitions ....................................................................................23
5.2.1.
Examination of Subgroups...........................................................24
5.3.
Other Considerations for Data Analyses and Data Handling 
Conventions................................................................................................25
6.
STUDY POPULATION ANALYSES .......................................................................26
6.1.
Overview of Planned Study Population Analyses........................................26
6.2.
Disposition of Subjects................................................................................26
6.3.
Demographic and Baseline Characteristics.................................................26
6.4.
Treatment Compliance................................................................................27
6.5.
Extent of Exposure .....................................................................................27
6.6.
Concomitant Medications............................................................................28
6.7.
Subsequent Anti-Cancer Therapies ............................................................29
7.
EFFICACY ANALYSES..........................................................................................30
7.1.
Primary Efficacy Analyses ..........................................................................30
7.2.
Secondary Efficacy Analyses......................................................................30


CONFIDENTIAL
BMA117159
5
7.2.1.
Multiple Myeloma.........................................................................30
7.2.1.1.
Endpoint / Variables ...................................................30
7.2.1.1.1.
Overall Response Rate...........................30
7.2.1.1.2.
Response Confirmation Algorithm ..........30
7.2.1.2.
Summary Measure .....................................................34
7.2.1.3.
Population of Interest..................................................34
7.2.2.
Lymphoma...................................................................................34
7.2.2.1.
Endpoint / Variables ...................................................34
7.2.2.1.1.
Overall Response Rate...........................34
7.2.2.2.
Summary Measure .....................................................34
7.2.2.3.
Population of Interest..................................................34
7.2.3.
Strategy for Intercurrent (Post-Randomization) Events ................34
7.2.4.
Statistical Analyses / Methods .....................................................35
7.3.
Exploratory Efficacy Analyses.....................................................................35
7.3.1.
Multiple Myeloma.........................................................................35
7.3.1.1.
Endpoint / Variables ...................................................35
7.3.1.2.
Summary Measure .....................................................35
7.3.1.2.1.
Progression-Free Survival ......................35
7.3.1.2.2.
Time to Progression................................38
7.3.1.2.3.
Duration of Response.............................39
7.3.1.2.4.
Time to Response ..................................39
7.3.1.2.5.
Time to Best Response ..........................39
7.3.1.2.6.
Overall Survival ......................................40
7.3.1.3.
Monoclonal Protein and Serum Free Light 
Chain..........................................................................40
7.3.1.4.
Subgroup Analysis of ORR.........................................41
7.3.1.5.
Population of Interest..................................................41
7.3.2.
Strategy for Intercurrent (Post-Randomization) Events ................41
7.3.3.
Statistical Analyses / Methods .....................................................41
8.
SAFETY ANALYSES .............................................................................................42
8.1.
Adverse Events Analyses ...........................................................................42
8.2.
Adverse Events of Interest Analyses...........................................................43
8.3.
Deaths and Serious Adverse Events...........................................................44
8.4.
Adverse Events Leading to Discontinuation of Study Treatment 
and/or Withdrawal from the Study and Other Significant Adverse 
Events ........................................................................................................45
8.5.
Pregnancies................................................................................................45
8.6.
Clinical Laboratory Analyses.......................................................................45
8.6.1.
Analyses of Liver Function Tests .................................................46
8.7.
Other Safety Analyses ................................................................................46
9.
PHARMACOKINETIC ANALYSES.........................................................................49
9.1.
Endpoint / Variables....................................................................................49
9.1.1.
Drug Concentration Measures .....................................................49
9.1.2.
Derived Pharmacokinetic Parameters..........................................49
9.1.2.1.
Non-compartmental Analysis......................................49
9.2.
Population of Interest..................................................................................50
9.3.
Statistical Analyses / Methods ....................................................................50
9.3.1.
Statistical Methodology Specification...........................................50
9.3.1.1.
Exploratory assessment of dose 
proportionality:............................................................50


CONFIDENTIAL
BMA117159
6
9.3.1.2.
Assessment of Accumulation Ratio: ...........................51
9.3.1.3.
Assessment of Analyte Ratios: ...................................53
9.3.2.
Model Checking & Diagnostics ....................................................54
10. POPULATION PHARMACOKINETIC (POPPK) ANALYSES..................................55
11. PHARMACODYNAMIC (AND / OR BIOMARKER) ANALYSES .............................56
12. PHARMACOKINETIC / PHARMACODYNAMIC ANALYSES .................................57
12.1.
Exposure-Response for Efficacy and Corneal Events.................................57
12.2.
Concentration-QTc Analyses ......................................................................57
13. HEALTH OUTCOMES ANALYSES........................................................................58
14. ANTI-DRUG ANTIBODY ANALYSES.....................................................................59
15. REFERENCES.......................................................................................................60
16. APPENDICES........................................................................................................61
16.1.
Appendix 1: Protocol Deviation Management and Definitions for Per 
Protocol Population.....................................................................................61
16.2.
Appendix 2: Schedule of Activities ..............................................................62
16.2.1.
Protocol Defined Schedule of Events...........................................62
16.2.2.
Dose Escalation...........................................................................63
16.2.2.1.
Every 3 Weeks Dosing Schedule for Multiple 
Myeloma.....................................................................63
16.2.2.2.
Weekly Dosing Schedule (Dose Escalation) for 
Multiple Myeloma .......................................................67
16.2.3.
Dose Expansion...........................................................................71
16.2.3.1.
Every 3 Weeks Dosing Schedule for Multiple 
Myeloma.....................................................................71
16.2.3.2.
Dose Expansion Weekly Dosing Schedule for 
Multiple Myeloma .......................................................76
16.2.3.3.
Dose Expansion Every 3 Weeks Dosing 
Schedule for Lymphomas...........................................80
16.2.3.4.
Dose Expansion Weekly Dosing Schedule for 
Lymphomas................................................................84
16.3.
Appendix 3: Assessment Windows .............................................................87
16.4.
Appendix 4: Study Phases and Treatment Emergent Adverse 
Events ........................................................................................................88
16.4.1.
Study Phases ..............................................................................88
16.4.1.1.
Study Time Periods for Concomitant 
Medications and Blood and Blood Supportive 
Care Products ............................................................88
16.4.2.
Treatment Emergent Flag for Adverse Events .............................89
16.5.
Appendix 5: Data Display Standards & Handling Conventions....................90
16.5.1.
Reporting Process .......................................................................90
16.5.2.
Reporting Standards....................................................................90
16.5.3.
Reporting Standards for Pharmacokinetic Data ...........................91
16.5.4.
Extended Loss to Follow-up or Extended Time without an 
Adequate Assessment.................................................................92
16.5.5.
Date Associated with Response ..................................................92
16.6.
Appendix 6: Derived and Transformed Data ...............................................93


CONFIDENTIAL
BMA117159
7
16.6.1.
General........................................................................................93
16.6.2.
Study Population..........................................................................93
16.6.3.
Efficacy........................................................................................93
16.6.4.
Safety ..........................................................................................94
16.7.
Appendix 7: Reporting Standards for Missing Data.....................................95
16.7.1.
Premature Withdrawals................................................................95
16.7.2.
Handling of Missing Data.............................................................95
16.7.2.1.
Handling of Missing and Partial Dates ........................96
16.8.
Appendix 8: Values of Potential Clinical Importance ...................................97
16.8.1.
Laboratory Parameters ................................................................97
16.8.2.
ECG Parameters and vital signs..................................................97
16.9.
Appendix 9: Population Pharmacokinetic (PopPK) Analyses ......................98
16.9.1.
Population Pharmacokinetic (PopPK) Dataset 
Specification ................................................................................98
16.9.2.
Population Pharmacokinetic (PopPK) Methodology...................115
16.10. Appendix 10: Pharmacokinetic / Pharmacodynamic Analyses ..................117
16.10.1. Pharmacokinetic / Pharmacodynamic Dataset 
Specification ..............................................................................117
16.10.2. Pharmacokinetic / Pharmacodynamic Methodology...................125
16.10.2.1. Exposure-Response Analyses..................................126
16.10.2.1.1. Corneal Events.....................................126
16.10.2.1.2. Clinical Response.................................126
16.11. Appendix 11: Abbreviations & Trade Marks ..............................................127
16.11.1. Abbreviations.............................................................................127
16.11.2. Trademarks ...............................................................................129
16.12. Appendix 12: List of Data Displays............................................................130
16.12.1. Data Display Numbering............................................................130
16.12.2. Mock Example Shell Referencing ..............................................130
16.12.3. Deliverables...............................................................................130
16.12.4. Study Population Tables............................................................131
16.12.5. Study Population Figures...........................................................149
16.12.6. Efficacy Tables ..........................................................................150
16.12.7. Efficacy Figures .........................................................................159
16.12.8. Safety Tables.............................................................................162
16.12.9. Safety Figures ...........................................................................201
16.12.10.Pharmacokinetic Tables.............................................................204
16.12.11.Pharmacokinetic Figures ...........................................................211
16.12.12.Pharmacokinetic / Pharmacodynamic (and / or Biomarker) 
Figures ......................................................................................217
16.12.13.ICH Listings ...............................................................................218
16.12.14.Non-ICH Listings........................................................................233
16.13. Appendix 13: Example Mock Shells for Data Displays ..............................245


CONFIDENTIAL
BMA117159
8
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:
Revision Chronology:
2012N155299_00
2013-DEC-26
Original
2012N155299_01
2014-MAR-01
Amendment No. 1. Country specific Amendment for the 
United Kingdom to address required changes per MHRA.  
Updated Exclusion Criteria to exclude subjects with current 
corneal disease or history of corneal disease.  Updated 
QTc withdrawal criterion to modify QTc withdrawal for QTc 
>500msec and to include > 60 msec increase from 
baseline.  Updated Data Management Section 12 to 
include details on dissemination of data and 
communication plan.  
2012N155299_02
2014-MAR-20
Amendment No. 2. Global Amendment to address required 
changes per the FDA.  Updated Inclusion Criteria with 
minimum weight requirement.  Updated Blood Volumes.  
Revised Time and Events Tables. Corrected typographical 
errors.
2012N155299_03
2014-MAY-05
Amendment No. 3. Country specific Amendment for 
Canada to address required changes per Health Canada.  
Updated preparation instructions of GSK2857916.
2012N155299_04
2016-MAY-05
Amendment No. 4. Global Amendment to include patient 
reported outcome instruments in the Part 2 multiple 
myeloma cohort and refine the lymphoma histologies 
eligible in Part 2 BCMA-expressing lymphoma cohort. 
Additionally, the requirement for 60% of tumor cells 
staining positive for BCMA expression was removed. The 
total number of subjects that may be enrolled is presented 
by a range of 80 to 95 to provide an updated estimate 
based on the number of subjects who enrolled at the time 
of the amendment.  Additional modifications include: 
changing the time-point specific blood specimens are 
collected for baseline/pre-treatment immunogenicity and 
biomarker measurements, and the visit window for certain 
assessments.
2012N155299_05
2017-NOV-02
Global amendment to include additional follow up of 
multiple myeloma subjects for ocular exams (for those 
whose corneal signs or symptoms have not resolved), 
additional patient reported outcome instruments, addition of 
time-to-event endpoints as exploratory objectives. Subjects 
who have completed treatment or the 3 month follow up 
visit (end of study) prior to amendment 5 will be 
reconsented for further follow up and survival status. Other 
administrative changes are also included


CONFIDENTIAL
BMA117159
9
1.1.
RAP Amendments 
Revision chronology: 
RAP Section
Amendment Details
Reporting and Analysis Plan_Study#_Final_V1 [26-JUN-2018]
Reporting and Analysis Plan_Study#_Amendment_Final_V1 [Insert Date]
Section 2.1 Changes to Protocol-
Specified Analysis Plan

Clarified that EOI concentration is not Cmax for cys-
mcMMAF

Clarified definition of urine PK interval parameters

Added analyte ratio determination and summaries
Section 5.2.2. Examination of 
Subgroups

Added a subgroup of “Penta-refractory”, defined as refractory to: 
Bortezomib and Carfilzomib and Lenalidomide and Pomalidomide 
and Daratumumab. Accordingly, the existing forest plot described 
in Section 7.3.1.4 Subgroup Analysis of ORR (exploratory 
analysis) will also include this added subgroup.
Section 8.7. Other Safety Analyses 
(Ocular Exam)

Added summary of best corrected visual acuity (BCVA) at 
additional visits (i.e. the last follow-up exam) to existing displays.

Added summary of subjects who experienced corneal clinical signs 
at additional visits (i.e. end of study treatment visit and last follow-
up exam) to existing displays
Section 9.1.2.1. Noncompartmental 
Analysis

Clarified that EOI concentration is not Cmax for cys-
mcMMAF

Clarified definition of urine PK interval parameters
Section 9.3.1.1. Exploratory 
assessment of dose proportionality 
(PK analyses)

Clarified that dose proportionality assessment is based on 
Part 1 Cycle 1 data
Section 9.3.1.2. Assessment of 
Accumulation Ratio (PK analyses)

Clarified definition of accumulation ratio for consistency with 
study design 

Changed analyses from model approach to descriptive 
statistics
Section 9.3.1.3. Assessment of 
Analyte Ratios (PK analyses)

Clarified definition of analyte ratio for consistency with study 
design

Changed analyses from model approach to descriptive 
statistics
Section 16.9.1. Population 
Pharmacokinetic (PopPK) Dataset 
Specification

Updated PopPK dataset specification
Section 16.10.1. Pharmacokinetic / 
Pharmacodynamic Dataset 
Specification

Updated PK/PD dataset specification
Section 16.12.4.Study Population 
Tables and Section 16.12.13.ICH 
Listings

Remove summary tables and listing of screening failure. The 
data was not collected


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2.
SUMMARY OF KEY PROTOCOL INFORMATION
2.1.
Changes to the Protocol Defined Statistical Analysis Plan
Changes from the originally planned statistical analysis specified in the protocol are 
outlined in Table 1.
Table 1
Changes to Protocol Defined Analysis Plan
Protocol
Reporting & Analysis Plan
Statistical Analysis Plan
Statistical Analysis Plan
Rationale for Changes

Time to response (TTR) is 
defined as the time between the 
date of first dose and the first 
documented evidence of 
response (PR or better). 
Subjects without confirmed 
response (PR or better) will be 
censored at the censoring date 
for TTP.

Time to response (TTR) is 
defined as the time 
between the date of first 
dose and the first 
documented evidence of 
response (PR or better), 
among subjects who 
achieve a response (i.e., 
confirmed PR or better).

To be consistent with GSK
Integrated Data Standards 
Library (IDSL) standard

Time to best response (TTBR) 
analyses was not planned.

Time to best response 
(TTBR), defined as the time 
between the date of first 
dose and the best response 
(PR or better), among 
subjects who achieve a 
response (i.e., confirmed 
PR or better), was added as 
an exploratory endpoint.

To further evaluate clinical 
activity of GSK2857916.

The ‘Pharmacokinetic (PK) 
Population’ is defined as those 
subjects in the “All Treated” 
population from whom at least 
one PK sample was obtained, 
analyzed, and was measurable.

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).

To be consistent with the 
latest GSK (IDSL) standard.

For cys-mcMMAF, after single 
dose, Cmax and AUC(0-t) will be 
derived and after repeat dose 
Cmax and Ctrough.

For cys-mcMMAF, after 
single dose, Cmax and 
AUC(0-t) will be derived 
and after repeat dose 
Ctrough.

Preliminary analysis of Part 
1 data found that cys-
mcMMAF Cmax did not 
occur at or near EOI in 
most cases; therefore, 
sparse sampling schedule 
did not measure cys-
mcMMAF Cmax.

Urinary recovery of unchanged 
cys-mcMMAF within the 24 h 
period collection (Ae(0-24)) will 
be calculated. Fraction of total 
cys-mcMMAF dose excreted 
(Fe) in the 24-h interval will be 

Urinary recovery of 
unchanged cys-mcMMAF 
within t hours after the start 
of infusion (Ae(0-t)) will be 
calculated.  Fraction of total 
cys-mcMMAF dose 

The 24-h urine collection 
period may start at a time 
other than the start of 
infusion; therefore, the urine 
collection period may not be 
24 h from the start of 


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Protocol
Reporting & Analysis Plan
Statistical Analysis Plan
Statistical Analysis Plan
Rationale for Changes
estimated as Ae(0-24)/cys-
mcMMAF Dose
excreted within t hours after 
the start of infusion (Fe(0-t)) 
will be estimated as 
Ae(0-t)/cys-mcMMAF dose.  
Time t is the time from the 
start of the infusion to the 
end of the urine collection 
period (24 h)..
infusion, and the 
pharmacokinetic parameter 
definitions have been 
changed to reflect this.

Not included

Calculation of analyte ratios 
as CEOI (total mAb, 
unbound mAb, or cys-
mcMMAF) to CEOI (ADC) 
or Ctrough (total mAb, 
unbound mAb, or cys-
mcMMAF) to Ctrough 
(ADC) at each cycle at 
which they are determined, 
adjusted for molecular 
weights

To assess exposures to 
each compound relative to 
ADC at EOI and trough for 
each cycle 

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

Descriptive statistics (mean, 
standard deviation, median, 
range) will be used to 
summarize change from 
baseline in observed value 
at each scheduled visit, as 
appropriate

To be consistent with the 
latest GSK (IDSL) standard.


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2.2.
Study Objective(s) and Endpoint(s)
Objectives
Endpoints
Primary Objectives
Primary Endpoints

To determine safety, tolerability, 
maximum tolerated dose (MTD), and 
recommended phase (RP2) dose and 
schedule of GSK2857916 
administered

Adverse events (AE) and changes in clinical signs and 
laboratory parameters
Secondary Objectives
Secondary Endpoints

To evaluate the pharmacokinetic (PK) 
profile of GSK2857916 and the 
breakdown product cys-mcMMAF
after intravenous (IV) single and 
repeat dose administration in subjects 
with relapsed/refractory MM and 
BCMA expressing lymphomas

GSK2857916 and cys-mcMMAF PK parameters following 
IV single and repeat dose administration during dose 
escalation as data permit (e.g., AUCs Cmax, tmax, CL, 
VSS, t½ [single dose], Cmax and Ctrough [repeat dose]).
GSK2857916 population PK parameters in expansion 
cohorts at the RP2 dose (e.g. clearance (CL), volume of 
distribution (Vd)), and relevant covariates which may 
influence exposure (e.g. age, weight, or disease-related 
covariates e.g. BCMA expression) 

To assess anti-drug antibody (ADA) 
formation after IV single and repeat 
dose administration of GSK2857916

ADA incidence and titers after single and repeat IV dosing 
of GSK2857916

To explore the initial anti-tumor activity 
of GSK2857916 in subjects with 
relapsed/refractory MM and BCMA 
expressing lymphomas

Clinical activity measured as Overall Response Rate 
(ORR) which is defined as follows:
o
For MM: the percentage of subjects achieving 
confirmed partial response or better (PR) 
o
In addition, the percentage of subjects with minimal 
response (MR) will be assessed for clinical benefit 
rate (CBR) (Appendix 1 of protocol)

For Lymphomas: the percentage of subjects achieving 
PR or better (PR) (Appendix 2 of protocol)
Exploratory Objectives
Exploratory Endpoints

To evaluate PD markers in MM after 
treatment with GSK2857916

sBCMA levels, BCMA receptor occupancy and cell death 
markers in subjects with MM. 

To explore relationships of 
GSK2857916 plasma 
concentrations/exposure with 
pharmacodynamics (PD), safety and 
clinical activity 

Relationship between receptor occupancy, tumor cell 
death markers, sBCMA and GSK2857916 plasma PK 
parameters;

Relationship between safety/clinical activity (e.g. ORR) 
and GSK2857916 PK parameters 

To characterize the relationship 
between clinical response and other 
biologic tumor characteristics (DNA, 
protein analysis)

BCMA expression levels on malignant cells as measured 
by IHC and/or flow cytometry in tumor tissue, serum 
sBCMA levels and their relationship to clinical response

To investigate the relationship 
between genetic variants in the host 
and response to study medicine, or 
susceptibility, severity and 
progression of disease 

Relationship between host genetic variation and response 
to study medicine or susceptibility, severity and 
progression of disease


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Objectives
Endpoints

To explore the effect of GSK2857916 
on symptoms (including bone pain, 
fatigue and visual symptoms) and 
impacts on HRQoL in subjects with 
relapsed/refractory MM (Part 2)

Changes from baseline in bone pain/fatigue and 
analgesic use as measured by the eDiary

Interviews with subjects to further characterize changes in 
symptoms (including bone pain/, fatigue and visual 
symptoms) and impacts on HRQoL

To explore changes in visual 
symptoms and function following 
discontinuation of treatment with 
GSK2857916

Changes in visual symptoms and impacts as measured 
by the OSDI and NEI-VFQ-25 following treatment 
discontinuation

Follow-up telephone interviews conducted to further 
understand subjects experience with visual symptoms 
and changes in symptoms and related impacts following 
treatment discontinuation

To explore the initial anti-tumor activity 
of GSK2857916 in subjects with 
relapsed/refractory MM in terms of 
time-to-event (TTE) endpoints (Part 2 
MM)

Time to progression (TTP), defined as: the time from 
first dose until the earliest date of PD per International 
Multiple Myeloma Working Group (IMWG), or death due 
to PD.

Duration of response (DOR), defined as: the time from 
first documented evidence of PR or better; until the time 
when disease progression (PD) is documented per 
IMWG; or death due to PD occurs in subjects who 
achieve a response, i.e. confirmed PR or better.

Time to response (TTR), defined as: the time between 
the date of first dose and the first documented evidence 
of response (PR or better), among subjects who achieve 
a response, i.e. confirmed PR or better. 

Time to best response (TTBR), defined as the time 
between the date of first dose and first documented 
evidence of the best response (PR or better), among 
subjects who achieve a response (i.e., confirmed PR or 
better).

Progression-free survival (PFS), defined as: the time 
from first dose until the earliest date of disease 
progression (PD) per IMWG, or death due to any cause.

Number of deaths.


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2.3.
Study Design
Overview of Study Design and Key Features
MTD1
4
3
1
2
25% of MTD1/RP2D1
MTD2/RP2D2
BCMA-positive Lymphomas (n =≈10)
Multiple myeloma  (n ≈ 40)
PART 1: Dose Escalation
(n≈30)
PART 2: Expansion Cohorts 
(n≈50)
2
3
1
*Cohort size to increase, n≈3 if ≥Grade 2 
drug related toxicity reported
5-9
4
RP2D1
Design
Features

Part 1 Dose Escalation 
o
Population: Subjects with relapsed/refractory MM (originally planned to enrol up 
to 30 subjects. However, additional subjects were enrolled to explore a new 
intermediate dose group)
o
Objective: characterize safety, PK, PD, immunogenicity and establish RP2 dose 
of GSK2857916
o
Two dosing schedules (Schedule 1 and Schedule 2) may be explored:

Schedule 1: GSK2587916 once every 3 weeks (21-day cycle) (n=~20)

Schedule 2: GSK2587916 once weekly for 3 consecutive weeks, 1-week rest 
(28-day cycle) (n=~9). Schedule 2 was not actually explored.
o
Serial PK samples will be collected from all subjects in Part 1

Part 2 Expansion Cohort(s) (n=~50 subjects)
o
Population: 

Subjects with relapsed/refractory MM (up to 40 subjects)

Subjects with lymphomas expressing BCMA (up to 10 subjects)
o
Objective: Further evaluate the safety, PK, immunogenicity, and clinical activity of 
GSK2857916 at the RP2 dose identified in Part 1
o
MM and Lymphoma expansion cohorts will be analyzed separately
o
Sparse PK samples will be collected from all subjects

Genetics research samples will be collected predose from all subjects


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Overview of Study Design and Key Features
Dosing

Part 1 Dose Escalation
Initially, GSK2857916 will be administered (IV) via 60 min infusion once every three 
weeks (21 days = 1 cycle) on Schedule 1. Once an MTD1 or RP2D has been 
established on the once every 21-day (Schedule 1), the safety, tolerability, PK, and 
PD of once-weekly dosing (Schedule 2) of GSK2857916 may be explored as an 
additional cohort(s).

Part 2: Dose Expansion Phase
Subjects enrolled in Part 2 dose expansion phase will be administered GSK2857916 
at recommended phase 2 dose (RP2D) established based on Part 1 outcomes.
Time & 
Events

Refer to Appendix 2: Schedule of Activities
Treatment 
Assignment

This is a non-randomized open-label study.
Interim 
Analysis

Part 1: Dose Escalation Phase
No formal interim analysis is planned for Part 1. Safety, pharmacokinetic and 
pharmacodynamic marker data will be examined on an ongoing basis to support dose 
escalation decisions.

Part 2: Dose Expansion Phase
o
For MM cohort, one futility analysis based on ORR data was performed after 
approximately 30 subjects are evaluable (originally 3 futility analyses are planned 
after approximately 15, 22 and 30 subjects are evaluable).
The number of confirmed responses (PR or better) observed will be compared 
with the stopping rules provided in Section 13.6.2 of the protocol.
o
For the lymphomas expressing BCMA cohort, no interim analyses will be 
performed, though consideration would be given to closing the cohort should the 
enrolment be stopped in the MM cohort.
2.4.
Statistical Hypotheses / Statistical Analyses
No formal statistical hypotheses will be tested in Part 1. Analysis of the data obtained 
from Part 1 will only utilize descriptive methods. In Part1, dose escalation/de-escalation 
decisions will be informed by the Bayesian approach: N-CRM (Neuenschwander-
Continuous Reassessment Method) [Neuenschwander, 2008]. Details of the N-CRM 
model used for this study is described in Section 3.1.1. 
The assumption for ORR in part 2 MM cohort is:
The null hypothesis H0: ORR ≤ 20% 
The alternative hypothesis HA: ORR ≥ 40%. 
No hypothesis testing is planned for part 2 MM cohort. The methodology utilized is 
based on the predictive probability of success if enrollment continues to 40 subjects [Lee, 
2008]. The predictive probability design is similar to a Green-Dahlberg design in that it 
allows for early stopping for futility. The differences are that the predictive probability 
design allows for evaluation of stopping rules as often as after each subject, rather than at 
only two stages.  While the two designs have similar type I and type II error rates, the 


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probability of early termination is greater with the predictive probability design. In this 
particular study, one futility analysis based on ORR data was performed after 
approximately 30 subjects are evaluable (originally 3 futility analyses are planned after 
approximately 15, 22 and 30 subjects are evaluable).
3.
PLANNED ANALYSES
3.1.
Interim Analyses
3.1.1.
Part 1: Dose Escalation Phase
While no formal interim analysis is planned for Part 1, safety, pharmacokinetic and 
pharmacodynamic marker data will be examined on an ongoing basis to support dose 
escalation decisions. Prior to determining the GSK2857916 dose for the next cohort 
enrolled, exploratory analysis will be conducted to assess the relationship of 
GSK2857916 dose levels with safety, PK and PD parameters using all data from 
available cohorts. 
Dose escalation/de-escalations decisions will take into account all available data, 
including but not limited to the safety parameters, PD and PK data of all cohorts 
assessed. Dose escalation/de-escalation decisions will be informed by the N-CRM 
(Neuenschwander-Continuous Reassessment Method) [Neuenschwander, 2008]. The N-
CRM model used for Schedule 1 is described in detail in Section 3.1.1.1 and Section 
3.1.1.2. The method is fully adaptive and makes use of all DLT information available at 
the time of each dose assignment. 
3.1.1.1.
Description of the New Continual Reassessment Method
The N-CRM is a type of Bayesian adaptive dose-escalation scheme that estimates the 
parameters of a statistical model relating dose and toxicity, and is expected to locate the 
MTD efficiently while minimizing the number of subjects exposed to pharmacologically 
inactive or unsafe dose levels. The method is fully adaptive and makes use of all the 
toxicity information available at the time of each dose assignment. N-CRM estimates 
may be provided at dose escalation meetings as supportive material to the primary 3+3 
dose escalation design.
The N-CRM estimates, for each potential dose, the (Bayesian) posterior probabilities that 
the DLT rate lies in each of four predefined toxicity ranges:

A dose falls in the Under-dosing range if the rate of a DLT at the dose is in the 
interval [0%, 16%).

A dose falls in the Target toxicity range if the rate of a DLT at the dose is in the 
interval [16%, 33%).

A dose falls in the Excessive toxicity range if the rate of a DLT at the dose is in the 
interval [33%, 60%).


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
A dose falls in the Unacceptable toxicity range if the rate of a DLT at the dose is in 
the interval [60%, 100%].
Additionally, the following over-dose constraints for the recommended dose will be 
maintained: 

The posterior probability of the DLT rate lying in the Excessive Toxicity or 
Unacceptable Toxicity range is 0.25 or less. 

The recommended dose is no more than 2 times that of the previous dose. 

Note that a de-escalation recommendation is possible using this method. At the time 
of each dose-escalation decision, the dose with the highest posterior probability of 
lying in the Target Toxicity range (subject to the given constraints) will be the 
model-recommended dose for the next cohort.
The N-CRM procedure for Schedule 1 will utilize a single subject/cohort run-in phase.
The single subject (small cohort) run-in will be halted when the first ≥ Grade 2 toxicity 
for which relationship to the investigational agent cannot be ruled out occurs in one 
subject in Cycle 1 (21 days).  At this point, the cohort will be expanded to 3 or more 
subjects at the same dose level and the escalation will continue to follow the N-CRM 
procedure as outlined in Table 2
Table 2
Single Subject (Small Cohort) Run-In Procedure for GSK2857916 
given on Schedule 1 (once every 21 days)
Dose Level 
Number of subjects 
with ≥G2 toxicity
Dose Escalation/Action
Dose Level 1/Cohort 1
0 out of 1 subject
(Sentinel subject)
Predicted starting dose 0.03 mg/kg every 21 days
Dose Level 2/Cohort 2
0 out of 1 subject
Escalate to the next dose level with increase   
≤100%  of the starting dose
Dose Level 3 and 
beyond/Cohort 3 and 
beyond
0 out of 1 subject
Escalate to the next dose level with increase of 
≤100% of the dose tested in the previous cohort 
1 out of 1 subject*
Switch to Cohort size of 3 or more subjects 
*Increase of doses up to 100% of the previous dose may continue until the first ≥ Grade 2 toxicity for which 
relationship to the investigational agent cannot be ruled out occurs in one subject in Cycle 1 (21 days).  At this point the 
single subject (small cohort) run-in is halted.  Continue with N-CRM, with cohort sizes of 3 or more subjects.  Increase 
of doses 100% will be considered for subsequent cohorts of 3 or more subjects. 
3.1.1.2.
Prior Probability Distribution 
Elicited prior probabilities of a DLT at each dose were used to determine the prior 
distribution of the parameters of an explicit logistic dose-toxicity model, namely


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,
where pd is the probability of a DLT at dose d, and dm is a reference dose. 
The prior distribution of (, ln()) will be assumed to be bivariate normal with means 
(standard deviations):  E[]=-1.3281 (1.7153), E[ln()]=-0.795 (1), with correlation 
between and ln() set to ρ=-0.9352 and dm=0.72 mg/kg.
3.1.1.3.
Displays To Be Created For Dose Escalation Review
Review of preliminary data will be performed after completion of each dosing cohort in 
Part 1. Preliminary safety and study population data may include a demographic 
summary, adverse event (AE) summary, AE summary by maximum toxicity category, 
SAE listing, listing of AEs that are reported to be DLT’s, and listing of AEs leading to 
dose modification. Spreadsheets containing relevant study data may also be supplied by 
the study data manager.
Further, after single subject run-in was halted, after each expanded cohort in dose 
escalation, the recommended dose from the N-CRM method and updated posterior 
estimates of the probabilities of being in each dose-toxicity range may be provided. The 
Fixed and Adaptive Clinical Trial Simulator (FACTS) (Version 2.4 or higher) software 
from Tessella will be used to make N-CRM calculations. 
Prior to determining a dose for the next cohort, exploratory analyses will be conducted to 
assess the relationship of dose levels with safety, PK, and pharmacodynamic parameters 
using all data from available cohorts.
The GSK study team, in collaboration with study investigators, will review all relevant 
data to support:

whether the current dose had acceptable toxicity, and

the decision regarding the next dose level based on the totality of the data
3.1.2.
Part 2 Expansion Phase
3.1.2.1.
Multiple Myeloma Expansion Cohort
During Part 2 (Expansion Cohort), futility analyses of response data will be conducted in 
order to determine whether the futility criteria for stopping have been met. The study will 
not be stopped early for efficacy, but is designed to stop early for futility if the predictive 
probability of success is less than 5%.
For Multiple Myeloma cohort, response data will be reviewed once approximately 30 
subjects are evaluable at the RP2D dose and the number of confirmed responses (PR, 
VGPR, CR, and sCR) will be compared with the stopping rules provided in Table 3 based 
on predictive probability design of Lee et al. [Lee, 2008].


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In addition to considering the recommendations of the futility analyses, final decisions on 
stopping enrolment in the MM cohort will depend on the totality of the data collected. 
Should the recommendation to stop for futility be disregarded in favour of a decision to
continue the trial based on the totality of the data, the overall type I error rate of the 
expansion phase will be inflated.
Table 3
Futility Stopping Region for Multiple Myeloma Expansion Cohort
Number of Overall Responses
Number of Evaluable Subjects
0
1
2
3
4
5
6
7
8
9
10
11
>11
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
3.1.2.1.1.
Operating Characteristics of the Stopping Rules for Futility
The stopping rule in Table 3 is based on the methodology of Lee et al. [Lee, 2008]. For 
the MM expansion cohort, starting with 15 subjects and allowing for a maximum sample 
size of 40, this design will have a type I error rate of 0.075 and 89.8% power. Under the 
null hypothesis, if the true response rate is 20%, the expected sample size of the design is 
23.4 subjects and probability of early termination (PET) is 88.9%.  Under the alternative 
hypothesis, if the true response rate is 40%, the expected sample size of the design is 38.6 
subjects and probability of early termination (PET) is 8.5%.


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3.1.2.2.
Lymphoma Expansion Cohort
No interim analyses will be performed on the BCMA positive lymphomas cohort; though 
consideration would be given to closing the cohort should the enrolment be stopped in the 
MM cohort.
3.2.
Administrative Interim Analyses
Additional administrative interim analysis may be performed to inform patient safety and 
efficacy of the drug as needed.
3.3.
Final Analyses
The final planned primary analyses will be performed after the completion of the 
following sequential steps:
1.
All participants have completed the study as defined in the protocol.
2.
All required database cleaning activities have been completed and final database 
release (DBR) and database freeze (DBF) has been declared by Data Management.
A final analysis of the MM population can be done separately, before the NHL cohort 
completes, and will necessitate separate DBR/DBF activities.


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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 (Reserve, Not Used) 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.

Sub-populations:
o
Part 1: all Part 1 subjects of All Treated 
population. Note, subjects in Part 1 are 
exclusively multiple myeloma patients. (2.5 mg/kg 
will be included in Part 1)
o
Part 2 MM: all Part 2 MM subjects of All Treated 
population
o
All Treated MM: comprise of subjects in Part 1 
and Part 2 MM.
o
Part 2 NHL: all Part 2 lymphoma subjects of All 
Treated population.

Study Population

Safety

Efficacy
Evaluable (MM)

This population is a subset of the ‘All Treated’ 
population, who were initially treated at RP2D in the 
expansion cohort and have at least two post-baseline 
disease assessments or they have progressed or died 
or permanently discontinued treatment. 

futility analyses of 
MM Expansion 
cohort only
DLT Evaluable

All subjects fulfilling the ‘All Treated’ population 
criteria, and having met the following adequate 
exposure criteria: 
o
For Schedule 1 (once every 3 weeks dosing) 
subjects received a complete infusion in cycle 1. 
o
For Schedule 2 (once weekly dosing for 3 
consecutive weeks, 1 week rest) subjects receive 
three infusions, two of which must be complete 
infusions, in cycle 1. (as increases up to ≤30% 
are implemented between cohorts, less than 2 
complete infusions would result in a total dose 
closer to the previous dose investigated). 
(Schedule 2 was not explored in the study)
o
Any subject in the “All Treated” population who 
experiences a DLT, as defined in Section 3.3.3 of 
the protocol will also be included in the DLT 
evaluable population regardless of exposure. 

Summary of DLT, 
for Part 1 only


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Population
Definition / Criteria
Analyses Evaluated
Pharmacodynamic 

The ‘Pharmacodynamic (PD) Population’ is defined as 
those subjects in the “All Treated” population from 
whom at least one PD sample was obtained, 
analyzed, and was measurable.

PD
Pharmacokinetic 
(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
Refer to Appendix 12: List of Data Displays which details the population used for each display.
4.1.
Protocol Deviations
Important protocol deviations (including deviations related to study inclusion/exclusion 
criteria, conduct of the trial, patient management or patient assessment) will be 
summarised and listed.
Protocol deviations will be tracked by the study team throughout the conduct of the study 
in accordance with the Protocol Deviation Management Plan [08May2017, Version 6.0].
o Data will be reviewed prior to freezing the database to ensure all important 
deviations are captured and categorised on the protocol deviations dataset. 
o This dataset will be the basis for the summaries and listings of protocol 
deviations.
A separate summary and listing of all inclusion/exclusion criteria deviations will also be 
provided. This summary will be based on data as recorded on the inclusion/exclusion 
page of the eCRF.


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5.
CONSIDERATIONS FOR DATA ANALYSES AND DATA
HANDLING CONVENTIONS
5.1.
Study Treatment & Sub-group Display Descriptors
Treatment Group Descriptions
RandAll NG
Data Displays for Reporting 
Code
Description [1]
Description [2]
Data Display
Order in TLF 
A
Active 
Treatment
GSK2857916 0.03 mg/kg (Part 1 MM) 
0.03 mg/kg  
1
GSK2857916 0.06 mg/kg (Part 1 MM)  
0.06 mg/kg  
2
GSK2857916 0.12 mg/kg (Part 1 MM)  
0.12 mg/kg  
3
GSK2857916 0.24 mg/kg (Part 1 MM)
0.24 mg/kg  
4
GSK2857916 0.48 mg/kg (Part 1 MM)
0.48 mg/kg  
5
GSK2857916 0.96 mg/kg (Part 1 MM)
0.96 mg/kg  
6
GSK2857916 1.92 mg/kg (Part 1 MM)
1.92 mg/kg
7
GSK2857916 2.50 mg/kg (Part 1 MM)
2.50 mg/kg
8
GSK2857916 3.40 mg/kg (Part 1 MM)
3.40 mg/kg
9
GSK2857916 4.60 mg/kg (Part 1 MM)
4.60 mg/kg
10
GSK2857916 3.40 mg/kg (Part 2 MM)
3.40 MM
11
GSK2857916 3.40 mg/kg (Part 2 NHL)
3.40 NHL
12
Notes: 
[1] This is a single-arm study and only active treatment is planned for the study.
[2] Part 1: dose escalation phase; Part 2: Expansion Cohort; MM: multiple myeloma; NHL: Lymphoma.
5.2.
Baseline Definitions
For all endpoints (except as noted in baseline definitions) the baseline value will be the 
latest pre-dose assessment with a non-missing value, including those from unscheduled 
visits. If time is not collected, Day 1 assessments are assumed to be taken prior to first 
dose and used as baseline.
For subjects who did not receive study treatment during the study, baseline will be 
defined as the latest, non-missing collected value.
For ECG analyses, subject level baseline is defined as the mean of triplicate baseline 
assessments.
Unless otherwise stated, if baseline data is missing no derivation will be performed and 
baseline will be set to missing.


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5.2.1.
Examination of Subgroups
The list of subgroups may be used in descriptive summaries. Additional subgroups of 
clinical interest may also be considered.
Subgroup
Categories 
Age
18 to <65, 65 to <75, >=75
Sex
Male, Female
Ethnic Background
White, Other
ISS Staging at Screening
I, II, III, Other (Unknown or Missing)
Number of prior lines of therapy
<=3,4-5, >5
Type of myeloma
IgG, Non-IgG
Prior Daratumumab Treatment
Yes, No
Refractory to prior anti-cancer 
therapy
Any Proteasome Inhibitor (PI)
    Bortezomib
    Carfilzomib
    Ixazomib
Any Immunomodulator (IMiD)
   Thalidomide
    Lenalidomide
    Pomalidomide
Monoclonal Antibodies
    Daratumumab
       Daratumumab alone [1]
       Daratumumab in combination [2]
    PI+IMiD
Daratumumab+PI+IMiD
Penta-refractory [3]
Cytogenetics Risk [4]W
High, Other (non-high risk, not done, or missing)
Prior anti-cancer therapy of 
interest

With prior Daratumumab Treatment and Refractory to Both 
Immunomodulators and Proteasome Inhibitors.

Without prior Daratumumab Treatment.

Refractory to Both Immunomodulators and Proteasome Inhibitors.
NOTES:
[1] Defined as prior CTX regimen with Daratumumab as the only drug in the regimen.
[2] Defined as prior CTX regimen with Daratumumab and other drugs in the regimen.
[3] Penta-refractory= refractory to: Bortezomib and Carfilzomib and Lenalidomide and Pomalidomide and 
Daratumumab.
[4] A subject is considered as high risk if the subject has any of the following cytogenetics: t(4;14), del17p, 
t(14;16).


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5.3.
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
16.3
Appendix 3: Assessment Windows
16.4
Appendix 4: Study Phases and Treatment Emergent Adverse Events
16.5
Appendix 5: Data Display Standards & Handling Conventions
16.6
Appendix 6: Derived and Transformed Data
16.7
Appendix 7: Reporting Standards for Missing Data
16.8
Appendix 8: Values of Potential Clinical Importance


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6.
STUDY POPULATION ANALYSES
6.1.
Overview of Planned Study Population Analyses
The study population analyses will be based on the “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, 
and exposure and treatment compliance will be based on GSK Core Data Standards.  
Details of the planned displays are presented in Appendix 12: List of Data Displays.
6.2.
Disposition of Subjects
A summary of the number of subjects in each of the analysis populations described in 
Section 4 will be provided (for final analysis, Evaluable population will not be included). 
In addition, the number of subjects enrolled by center will be summarized by Study Part 
and Tumor Type using the “Enrolled” population. A separate summary for exclusions 
from each study population will be displayed (for final analysis, Evaluable population 
will not be included). A listing of subjects excluded from analysis populations will also 
be provided.
A summary of subject status and reason for study withdrawal will be provided. This 
display will show the number and percentage of subjects who withdrew from the study, 
including primary reasons for study withdrawal. Reasons for study withdrawal will be 
presented in the order they are displayed in the eCRF. 
A summary of study treatment status will be provided. This display will show the number 
and percentage of subjects who are ongoing or discontinued study treatment and a 
summary of the primary reasons for discontinuation of study treatment. Reasons for study 
treatment discontinuation will be presented in the order they are displayed in the eCRF. A
listing of study treatment discontinuation will be generated. The listing will include last 
dose date, and reasons for study treatment discontinuation. 
6.3.
Demographic and Baseline Characteristics
The demographic characteristics (e.g., age, race, ethnicity, sex, baseline height, and 
baseline body weight and baseline BMI will be summarized and listed. Age, height,
weight and BMI will be summarized using the mean, standard deviation, minimum, 
median, and maximum. The count and percentage will be computed for sex and ethnicity.
Race and racial combinations will be summarized and listed.
Disease history and characteristics (e.g. time since initial diagnosis in years, stage at 
initial diagnosis, date of initial diagnosis) at initial diagnosis and screening will be listed. 
Separate summaries of disease characteristics at initial diagnosis and screening will be 
provided. Disease characteristics 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 summarized and listed.


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Medical conditions present at screening will be listed and will be summarized by past and 
current and by cancer-related and non-cancer related categories. 
Genetic characteristics for multiple myeloma subjects at screening will be summarized 
and listed. Cytogenetic risk for multiple myeloma subjects at screening will be 
summarized. A subject is considered as having high cytogenetic risk if the subject has 
any of the following cytogenetics: t(4;14), del17p, t(14;16).
Substance use, including smoking history and alcohol use will be summarized and listed.
Prior anti-cancer therapy will be coded using GSK Drug coding dictionary, then 
summarized by type of therapy and listed. A listing of prior anti-cancer therapy will show 
the relationship between ATC Level 1, Ingredient, and verbatim text. A summary of the 
best response to the most recent prior anti-cancer therapy will be provided. A summary of 
the number of prior anti-cancer therapy regimens will also be produced. 
Prior anti-cancer therapy for multiple myeloma subjects will also be summarized by type 
of therapy, drug class and subclass. A summary of multiple myeloma subjects refractory 
to prior anti-cancer therapy by drug class will be provided. 
A multiple myeloma subject is defined to be refractory to prior anti-cancer therapy if 
[1] the subject’s best response to prior anti-cancer therapy is PD or SD, OR
[2] the subject’s most recent response to prior anti-cancer therapy is PD or SD, OR
[3] the subject progress within 60 days of completion of prior anti-cancer therapy.
Summary of subjects with multiple myeloma double refractory to prior 
Immunomodulator (IMID) and Proteasome Inhibitor (PI) will also be provided. For 
definition of “double refractory”, IMID and PI are not necessary to be in the same 
regimen.
Anti-cancer radiotherapy will be listed. Prior cancer and non-cancer related surgeries will 
be summarized. Prior and on treatment cancer and non-cancer related surgeries will be 
listed. 
6.4.
Treatment Compliance
Summaries of study treatment exposure and dose modifications (e.g., number of dose 
reductions, number of dose interruptions) will further characterize compliance. These 
analyses are described in Section 6.5 ‘Extent of Exposure’.
6.5.
Extent of Exposure
Extent of exposure to GSK2857916 will be summarized.
The number of cycles administered to study treatment will be summarised with mean, 
median, standard deviation, minimum, and maximum. The number and percentage of 
subjects who received a given number of cycles (<4, 4, and >4 cycles) will be reported. 


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Dose intensity (dose delivered per cycle) will be summarized using mean, median, 
standard deviation, minimum, and maximum by cycle and overall. Dose intensity is the 
cumulative actual dose divided by the total number of cycles across the entire treatment 
period. 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 1-21, 22-42 and >42 days will 
be computed. Primary reasons for dose reductions and dose delays will also be 
summarized by cycle. 
Duration of delays is defined as period from the expected start date of dose to actual start 
date of current dose. Calculation: (actual start date of current dose - expected start date of 
dose). Expected start date of dose = actual start date of previous dose + 21.
The summaries of dose modifications will be provided only if the data warrant.
All the dose reductions, dose escalations, infusion interruptions, incomplete infusions and 
dose delays will be listed separately.
A plot showing the number and percentage of subjects treated at different dose levels 
over time will be provided.
The duration of exposure to study treatment in days (from first day to last day of 
treatment) will be calculated. A horizontal bar graph of duration of treatment will be 
produced that displays duration of treatment in days for each subject.
6.6.
Concomitant Medications
Concomitant medications will be coded using GSK Drug coding dictionary, summarized, 
and listed. The summary of concomitant medications will show the number and 
percentage of subjects taking concomitant medications by Ingredient. Multi-ingredient 
products will be summarized by their separate ingredients rather than as a combination of 
ingredients. Anatomical Therapeutic Chemical (ATC) classification Level 1 (Body 
System) information will be included in the dataset created but will not appear on the 
listing or summary. 
Prophylactic Medication for Infusion-Related Reactions will be summarized by drug 
class and drug name and listed separately. Eye medications will be listed.
In the summary of concomitant medications, each subject is counted once within each 
unique ingredient. For example, if a subject takes Amoxycillin on two separate occasions, 
the subject is counted only once under the ingredient “Amoxycillin”. In the summary of 
concomitant medications, the ingredients will be summarized by the base only, using 
CMBASECD and CMBASE. Note: In order to be considered a concomitant medication, 
the concomitant medication must have been taken at some point during the on-therapy 
window.


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Blood products or blood supportive care products with onset date within the on-therapy 
window will be included in the summary tables. The frequency and percentage of 
subjects using blood products and blood supportive care products after the start of study 
medication will be provided. Supporting listings will also be provided.
6.7.
Subsequent Anti-Cancer Therapies
The number and percentage of subjects that received chemotherapy, immunotherapy, 
hormonal therapy, biologic therapy, radioactive therapy, small molecule targeted therapy, 
as post study treatment anti-cancer therapy will be summarized. Time from study 
treatment discontinuation to the first post study treatment anti-cancer therapy will also be 
included in this summary table. 
Follow-up anti-cancer therapy will be coded using GSK Drug coding dictionary, then 
summarized by ingredient. A listing of the type of follow-up anti-cancer therapy received 
(chemotherapy, immunotherapy, hormonal therapy, biologic therapy, radioactive therapy, 
and small molecule targeted therapy for each subject will be provided).


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7.
EFFICACY ANALYSES
7.1.
Primary Efficacy Analyses
No primary efficacy analyses were planned.
7.2.
Secondary Efficacy Analyses
Details of the planned displays are provided in Appendix 12: List of Data Displays and 
will be based on GSK data standards and statistical principles.
Unless otherwise specified, endpoints / variables defined in Section 7.2.1.1 and Section 
7.2.2.1 will be summarised using descriptive statistics, graphically presented (where 
appropriate) and listed.
7.2.1.
Multiple Myeloma
7.2.1.1.
Endpoint / Variables
7.2.1.1.1.
Overall Response Rate
Overall Response Rate (ORR), is defined as the percentage of responders (subjects with 
confirmed stringent complete response (sCR), complete response (CR), very good partial 
response (VGPR), and partial response (PR) as assessed according to 2011 International 
Myeloma Working Group (IMWG) criteria (Appendix 1 in the protocol) ). Only the 
assessments from the start of treatment up to the earlier of disease progression or the start 
of new anti-cancer therapy will be considered. Only new systemic anti-cancer drugs 
taken are considered as anti-cancer therapy (radiotherapy and surgeries are not 
considered as systemic anti-cancer therapy for the purpose of this analysis). . 
Subjects with only one assessment (therefore not confirmed), or assessments of Not 
Evaluable or missing response will be treated as non-responders; i.e. they will be 
included in the denominator when calculating the percentage.
7.2.1.1.2.
Response Confirmation Algorithm
The definitions and details to derive unconfirmed and confirmed response are outlined 
below. For both confirmed and unconfirmed response derivations, only responses 
assessments from the start of treatment up to the earlier of disease progression or the start 
of new anti-cancer therapy will be considered. Date associated with response was defined 
in Section 16.5.5
Definitions:
1. The hierarchy of response classifications from high to low is as following: 
sCR, CR, VGPR, PR, MR, SD, PD and NE. Response was assessed according 
to the 2011 Uniform Criteria Consensus recommendations of the International 
Myeloma Working Group (See Appendix 1 of protocol).


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2. Definition of two consecutive assessments: the two consecutive assessments 
should be taken from two different samples, and NOT based upon the splitting 
of a single sample.
a.
No minimum time separation between two consecutive assessments is 
required to confirm response.
b. If there are two assessments separated by not evaluable (NE) or 
Missing assessment(s), collapse data by ignoring NE or Missing 
assessments. 
c.
If two consecutive assessments are on different dates, it is assumed 
that the two assessments are from different samples
d. If there are multiple assessments on the same date and there is no data 
to show that they are from different samples, it is assumed these 
assessments are from the same sample. Then only the response with 
the lowest magnitude will be selected as the response for that date.
Two-step algorithm for determining the best confirmed response
Step1. Determine the confirmed response sequentially at each time of disease assessment.
A. For confirmed sCR, CR, VGPR, PR, MR, SD, two consecutive assessments are 
required. 
a.
For any two consecutive assessments with different magnitudes, the confirmed 
response is the response of lower magnitude.
b. For any two consecutive assessments with the same magnitude, the confirmed 
response is the response of that magnitude.
c.
Although the response will be confirmed at the time of the second one of the two 
consecutive assessments, the date of the first one of the two consecutive 
assessments will be the date of this confirmed response.
Table 4
Summary of the criteria for confirmation of sCR, CR, VGPR, PR, MR, 
SD
Response at one time-point of two 
consecutive assessments
Response at the other time-point 
of two consecutive assessments
Confirmed 
Response
sCR/CR/VGPR/PR/MR/SD
SD
SD
sCR/CR/VGPR/PR/MR
MR
MR
sCR/CR/VGPR/PR
PR
PR
sCR/CR/VGPR
VGPR
VGPR
sCR/CR
CR
CR
sCR
sCR
sCR


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B. For PD, since for this study, no confirmation of PD is required, only one PD 
assessment is required. Any PD assessment will be confirmed by itself at the time of 
the PD’s assessment.
C. If the subject has only one non-PD /non-NE assessment then the confirmed response 
is NE at the date of that assessment.
D. If all assessments were NE then the confirmed response is NE at the date for each 
assessment.
Step 2. Determine the best overall confirmed response in Step 1. If assessments at all 
visits are missing then the best confirmed response is NE.
Examples: 
Example 1.
Step1. 
Visit
Response
Confirmed 
response
1
PR
2
SD
SD
3
SD
SD
Step 2. 
The best overall confirmed response is SD 
Example 2.
Step1. 
Visit
Response
Confirmed 
response
1
VGPR
2
NE
3
NE
4
PR
PR
Step 2. 
The best overall confirmed response is PR 


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Example 3.
Step1. 
Visit
Response
Confirmed 
response
1
sCR
2
sCR
sCR
3
CR
CR
4
PR
PR
Step 2. 
The best overall confirmed response is sCR 
Example 4.
Step1. 
Visit
Response
Confirmed 
response
1
sCR
2
CR
CR
3
CR
CR
4
PR
PR
Step 2. 
The best overall confirmed response is CR 
Example 5.
Step1. 
Visit
Response
Confirmed 
response
1
CR
2
VGPR
VGPR
Step 2. 
The best overall confirmed response is VGPR.


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7.2.1.2.
Summary Measure
Overall response rate (ORR) and the associated 2-sided 95% exact confidence intervals 
will be provided by dose level and study part. In addition, Clinical Benefit Rate (CBR), 
defined as the percentage of subjects with minimal response (MR) will be summarized 
in the same way as ORR by dose level and study part. Unconfirmed response summaries 
may be provided for interim analyses. A list of investigator-assessed response at each 
visit will be listed.
7.2.1.3.
Population of Interest 
The secondary efficacy analyses will be based on the “All Treated” population, unless 
otherwise specified. Response data for multiple myeloma will be summarized by Study 
Part using the All Treated MM population and in subgroup: Prior anti-cancer therapy of 
interest as defined in Section 5.2.1.
7.2.2.
Lymphoma
7.2.2.1.
Endpoint / Variables
7.2.2.1.1.
Overall Response Rate
For lymphoma patients, clinical activity for lymphomas will be calculated based on ORR 
defined as the percentage of subjects with confirmed CR or PR, as described in the 
Revised Response Criteria for Malignant Lymphoma (RRCML, Appendix 2 in the 
protocol) from the start of treatment until disease progression or the start of new anti-
cancer therapy. 
A summary of investigator-assessed best response with confirmation will be presented. 
Subjects with Not Evaluable or missing response will be treated as non-responders; and 
they will be included in the denominator when calculating the percentage. To be assigned 
a status of complete response or partial response, all responses must be confirmed by 
repeat assessments performed no less than four weeks after the criteria for CR or PR were 
met (RRCML, Appendix 2 in the protocol).
7.2.2.2.
Summary Measure
Overall response rate and the associated 2-sided 95% exact confidence intervals will be 
provided. A list of investigator-assessed response at each visit will be listed.
7.2.2.3.
Population of Interest 
The secondary efficacy analyses will be based on the “All Treated” population, unless 
otherwise specified. Response data for lymphoma will be summarized using the Part 2 
NHL population.
7.2.3.
Strategy for Intercurrent (Post-Randomization) Events
Not applicable to this study.


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7.2.4.
Statistical Analyses / Methods
Details of the planned displays are provided in Appendix 12: 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.
7.3.
Exploratory Efficacy Analyses
7.3.1.
Multiple Myeloma
7.3.1.1.
Endpoint / Variables
Time-to-event endpoint - Multiple Myeloma
Progression-Free 
Survival (PFS)
defined as the time from first dose until the earliest date of confirmed 
disease progression (PD) per IMWG (2011), or death due to any cause.
Time to 
Progression (TTP)
defined as the time from first dose until the earliest date of PD per IMWG 
(2011), or death due to PD.
Duration of 
Response (DOR)
defined as the time from first documented evidence of confirmed PR or 
better until the time when disease progression (PD) is documented per 
IMWG (2011), or death due to PD among subjects who achieve a 
response (i.e. confirmed PR or better). 
Time to Response 
(TTR)
defined as the time between the date of first dose and the first documented 
evidence of confirmed response (PR or better), among subjects who 
achieve a response (i.e., confirmed PR or better). 
Time to Best 
Response (TTBR)
defined as the time between the date of first dose and the best confirmed 
response (PR or better), among subjects who achieve a response (i.e., 
confirmed PR or better).
Overall survival 
(OS)
defined as the time from the date of first dose until death from any cause.
In addition, monoclonal protein and serum free light chain lab test values will be plotted. 
Subgroup analysis for ORR will be performed 
7.3.1.2.
Summary Measure
7.3.1.2.1.
Progression-Free Survival
PFS is defined as the interval of time between the date of first dose and the earlier of the 
date of first disease progression and the date of death due to any cause. Disease 
progression will be based on the assessments by the Investigator. 
If there is no adequate baseline assessment, the subjects will be censored at their date of 
first dose. Subjects without any adequate post-baseline tumor assessments will be 
censored at the date of first dose.


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Subjects who progressed or died after an extended period without adequate assessment 
will be censored at their date of last adequate assessment prior to progression or death 
even if subsequent information is available regarding progression or death. An adequate 
assessment is defined as an assessment where the Investigator determined response is 
sCR, CR, VGPR, PR, MR or SD. The date of response at that assessment will be used for 
censoring. As the assessment schedule may change through the course of the protocol, 
specific rules for identifying extended loss to follow-up or extended time without an 
adequate assessment are provided in Section 16.5.4.
For subjects who receive subsequent anti-cancer therapy the following rules will apply:

If the start date of the anti-cancer therapy is partial (i.e. either missing the day but 
has the month and year available or missing both day and month), the imputation 
rules described in Section 16.7.2.1 will be applied. No imputation will be made for 
completely missing dates.

If anti-cancer therapy is started without documented disease progression or death OR 
is started prior to documented disease progression or death, then PFS will be 
censored at the date of the last adequate assessment that is no later than the date of 
initiation of anti-cancer therapy (i.e. if an assessment occurs on the same day as the 
start of new anti-cancer therapy the assessment will be used - as it will be assumed 
the assessment occurred prior to the administration of new anti-cancer therapy). The 
date of response at the last adequate assessment will be used as the censoring value.

If a subject has only a baseline visit or does not have an adequate assessment that is 
no later than the date of initiation of anti-cancer therapy, PFS will be censored at the 
date of first dose.

If a subject has neither progressed nor died nor started new anti-cancer therapy, then 
PFS will be censored at the date of the last adequate assessment defined as an 
assessment where the Investigator determined response is sCR, CR, VGPR, PR, MR 
or SD. The date of response will be used as the censoring date.
A summary of the assignments for progression and censoring dates for PFS are specified 
in Table 5.


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Table 5
Assignments for Progression and Censoring Dates for PFS Analysis
Situation
Date of Event 
(Progression/Death) or 
Censoring 
Outcome Event 
(Progression/Death) Or 
Censored
No (or inadequate) baseline 
tumor assessments [1] and the 
subject has not died (if the subject 
has died follow the rules for death 
indicted at the bottom of the table)
First dose date
Censored
No post-baseline assessments 
and the subject has not died (if 
the subject has died follow the 
rules for death indicted at the 
bottom of the table)
First dose date
Censored
Progression documented 
between scheduled visits
Date of assessment of 
progression [1]
Event
No progression (or death)
Date of last ‘adequate’ 
assessment of response [2]
Censored
New anticancer treatment started 
(prior to documented disease 
progression or death) [3].
Date of last ‘adequate’ 
assessment of response [2] (on or 
prior to starting anti-cancer 
therapy) 
Censored
Death before first PD assessment 
(or Death at baseline or prior to 
any adequate assessments)
Date of death
Event
Death between adequate 
assessment visits 
Date of death
Event
Death or progression after an 
extended loss-to-follow-up time 
(two or more missed cycles + 7 
day window) [4]
Date of last ‘adequate’ 
assessment of response [2] (prior 
to missed assessments)
Censored
1. In part 1, adequate baseline assessment is defined as at baseline, a patient has at least one of the following 
measurements: a. Serum M-protein or b. Urine M-protein or c. Serum FLC assay or d. Biopsy proven plasmacytoma 
(should be measured within 28 days of Screening Visit). 
In part 2, adequate baseline assessment is defined as at baseline, a patient has at least one of the following 
measurements: a. Serum M-protein ≥0.5 g/dL (≥5 g/L) or b. Urine M-protein ≥200 mg/24h or c. Serum FLC assay: 
Involved FLC level ≥5 mg/dL (≥50 mg/L) and an abnormal serum free light chain ratio (<0.26 or >1.65) or d. Biopsy 
proven plasmacytoma (should be measured within 28 days of Screening Visit and no later than the first dose date).
2. An adequate assessment is defined as an assessment where the Investigator determined response is sCR, CR, 
VGPR, PR, MR, or SD.
3. If PD or death and New anti-cancer therapy occur on the same day assume the progression or death was 
documented first (e.g., outcome is progression or death and the date is the date of the assessment of progression or 
death). If anti-cancer therapy is started prior to any adequate assessments, censoring date should be the date of first 
dose.
4. Refer to Section 16.5.4 “Extended Loss to Follow-up or Extended Time without an Adequate Assessment”.
PFS will be summarized using Kaplan-Meier curves. If there are a sufficient number of 
progressions or deaths, median PFS, first and third quartiles and 95% CI, will be 
estimated using the Brookmeyer-Crowley method [Brookmeyer, 1982]. A figure and 
listing of PFS time will also be provided. Summary and figure of PFS will be based on 


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Part 2 MM sub-population and subgroup prior anti-cancer therapy of interest; listing of 
PFS will be based on All Treated MM population.
7.3.1.2.2.
Time to Progression
TTP is defined as the interval of time between the date of first dose and the earlier of the 
date of first documented evidence of PD, or death due to PD, whichever occurs first.
A summary of the assignments for progression and censoring dates for TTP are specified 
in Table 6
Table 6
Assignments for Progression and Censoring Dates for TTP Analysis
Situation
Date of Event 
(Progression/Death) or 
Censoring 
Outcome Event 
(progression/Death) Or 
Censored
No (or inadequate) baseline 
tumor assessments [1] and the 
subject has not died (if the subject 
has died follow the rules for death 
indicted at the bottom of the table)
First dose date
Censored
No post-baseline assessments 
and the subject has not died (if 
the subject has died follow the 
rules for death indicted at the 
bottom of the table)
First dose date
Censored
Progression documented at or 
between scheduled visits
Date of assessment of 
progression [1]
Event
No progression (or death)
Date of last ‘adequate’ 
assessment of response [2]
Censored
New anticancer treatment started 
(prior to documented disease 
progression or death) [3].
Date of last ‘adequate’ 
assessment of response [2] (on or 
prior to starting anti-cancer 
therapy) 
Censored
Death from causes other than 
progression
Date of death
Censored
Death or progression after an 
extended loss-to-follow-up time 
(two or more missed cycles + 7 
day window) [4]
Date of last ‘adequate’ 
assessment of response [2] (prior 
to missed assessments)
Censored
[1] In part 1, adequate baseline assessment is defined as at baseline, a patient has at least one of the following 
measurements: a. Serum M-protein or b. Urine M-protein or c. Serum FLC assay or d. Biopsy proven plasmacytoma 
(should be measured within 28 days of Screening Visit). 
In part 2, adequate baseline assessment is defined as at baseline, a patient has at least one of the following 
measurements: a. Serum M-protein ≥0.5 g/dL (≥5 g/L) or b. Urine M-protein ≥200 mg/24h or c. Serum FLC assay: 
Involved FLC level ≥5 mg/dL (≥50 mg/L) and an abnormal serum free light chain ratio (<0.26 or >1.65) or d. Biopsy 
proven plasmacytoma (should be measured within 28 days of Screening Visit and no later than the first dose date).
[2] An adequate assessment is defined as an assessment where the Investigator determined response is sCR, CR, 
VGPR, PR, MR, or SD.
[3] If PD and New anti-cancer therapy occur on the same day assume the progression was documented first e.g., 
outcome is progression and the date is the date of the assessment of progression). If anti-cancer therapy is started 
prior to any adequate assessments, censoring date should be the date of first dose. Refer to Section 16.5.4 “Extended 
Loss to Follow-up or Extended Time without an Adequate Assessment”.


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TTP will be summarized using Kaplan-Meier curves. If there are a sufficient number of 
progressions or death due to PD, median TTP, first and third quartiles and 95% CI, will 
be estimated using the Brookmeyer-Crowley method [Brookmeyer, 1982]. A figure and 
listing of TTP time will also be provided. Summary and figure of TTP will be based on 
Part 2 MM population; listing of TTP will be based on All Treated MM population.
7.3.1.2.3.
Duration of Response
Duration of Response (DOR) is defined, for subjects with a confirmed response (PR or 
better) as the time between first documented evidence of confirmed response and disease 
progression or death due to PD, whichever occurs first.

Duration of response is derived for patients with a confirmed PR or better only. 

Censoring rules will follow those of the TTP analysis.
DOR will be summarized using Kaplan-Meier curves. If there are a sufficient number of 
progressions or death due to PD among the responders, median DOR, first and third 
quartiles and 95% CI, will be estimated using the Brookmeyer-Crowley method 
[Brookmeyer, 1982]. A figure and listing of DOR time will also be provided. Summary 
and figure of DOR will be based on Part 2 MM population and subgroup: prior anti-
cancer therapy of interest; listing of DOR will be based on All Treated MM population.
7.3.1.2.4.
Time to Response
Time to Response (TTR) is defined as the time from first dose to the first documented 
evidence of confirmed PR or better, among subjects who achieve a response (i.e., 
confirmed PR or better).
TTR will be summarized using Kaplan-Meier method. If data permits, median TTR, first 
and third quartiles and 95% CI, will be estimated using the Brookmeyer-Crowley method 
[Brookmeyer, 1982]. A listing of TTR time will also be provided. Summary of TTR will 
be based on Part 2 MM population; listing of TTR will be based on All Treated MM 
population.
7.3.1.2.5.
Time to Best Response
Time to Response (TTBR) is defined as the time from first dose to the best confirmed 
response (PR or better), among subjects who achieve a response (i.e., confirmed PR or 
better).
TTBR will be summarized using Kaplan-Meier method. If data permits, median TTBR, 
first and third quartiles and 95% CI, will be estimated using the Brookmeyer-Crowley 
method [Brookmeyer, 1982]. A listing of TTBR time will also be provided. Summary of 
TTBR will be based on Part 2 MM population; listing of TTBR will be based on All 
Treated MM population.


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7.3.1.2.6.
Overall Survival
Overall survival (OS) is defined as the time from the date of first dose until death from 
any cause. For subjects who do not die, time of death will be censored at the date of last 
contact.
The protocol is amended to collect long-term survival data (i.e. up to 1 year after last 
subject completes or discontinues treatment). Subjects who are already completed the 
study will be contacted to request re-consent.
If all the patients (who were alive at the time of study completion) can be re-consented, 
OS landmark analysis may be performed at 9 and 12 months using Kaplan-Meier analysis 
as data permits. A listing of OS will also be provided. The OS landmark analysis will be 
based on Part 2 MM population; listing of OS will be based on All Treated MM 
population.
Otherwise, only descriptive analysis (number and % of deaths and lost to follow-up) will 
be performed.
7.3.1.3.
Monoclonal Protein and Serum Free Light Chain
A waterfall plot showing the maximum percent reduction from baseline in Serum M-
protein, or Urine M-protein, or difference between two types Serum FLC [Kappa light 
chain (Kappa LC) and Lambda light chain (Lambda LC)] for each subject will be 
produced using Part1 and Part 2 MM populations. Only the assessments from the start of 
treatment up to the start of new anti-cancer therapy will be considered. Only new 
systemic anti-cancer drugs taken are considered as anti-cancer therapy (radiotherapy and 
surgeries are not considered as systemic anti-cancer therapy for the purpose of this 
analysis). The maximum percent reduction will be plotted in the following hierarchical 
order: 
[1] Plot Serum M-protein maximum percent reduction from baseline if data is 
available;
[2] If [1] is not feasible, plot Urine M-protein maximum percent reduction from 
baseline if data is available;
[3] If both [1] and [2] are not feasible, plot maximum percent reduction from baseline
for difference between two types of Serum FLC if data is available;
Difference between two types Serum FLC
The percent change from baseline for difference between two types of Serum FLC is 
defined as: 
(post-baseline difference-baseline difference) / baseline difference *100%
To calculate the difference, the “involved” and “non-involved” light chains must be 
determined at first based on the ratio of non-missing values for Serum Kappa LC protein 
and Serum Lambda LC protein at baseline.


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Detailed algorithm is provided as below:

If the baseline ratio of (Kappa LC/Lambda LC)>1.65, then Kappa LC is defined as 
involved FLC, and Lambda LC is defined as non-involved FLC. Then
o
Difference between involved and uninvolved = Kappa LC-Lambda LC

If the baseline ratio of (kappa/lambda)<0.26, then Lambda light chain is defined as 
involved FLC, and Kappa light chain is defined as non-involved FLC
o
Difference between involved and uninvolved = Lambda LC-Kappa LC

If the baseline ratio of (Kappa LC/Lambda LC) 1.65 and 0.26, then “involved” 
and “non-involved” FLC can not be determined (ratio is normal), and maximum 
percent reduction from baseline for difference between two types of Serum FLC
won’t be available.
In addition, a scatter plot of free soluble BCMA at pre-dose (cycle 1) and maximum 
percent change from baseline in Serum M-protein, Urine M-protein or difference between 
two types Serum FLC will be provided following the hierarchical order specified above.
7.3.1.4.
Subgroup Analysis of ORR
A forest plot of ORR analysis will be provided for the following subgroups: Age, Sex, 
Ethnic Background, ISS Staging at Screening, Number of prior lines of therapy, Type of 
myeloma, Prior Daratumumab Treatment, Refractory to prior anti-cancer therapy, 
Cytogenetics Risk as defined in Section 5.2.1.
7.3.1.5.
Population of Interest 
The secondary efficacy analyses will be based on the “All Treated” population, unless 
otherwise specified (as in Section 4). 
7.3.2.
Strategy for Intercurrent (Post-Randomization) Events
Not applicable to this study.
7.3.3.
Statistical Analyses / Methods
Details of the planned displays are provided in Appendix 12: List of Data Displays and 
will be based on GSK data standards and statistical principles.
Unless otherwise specified, endpoints / variables defined in Section 7.2.1 will be 
summarised using descriptive statistics, graphically presented (where appropriate) and 
listed.


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8.
SAFETY ANALYSES
The safety analyses will be based on the “All Treated” population, unless otherwise 
specified.
8.1.
Adverse Events Analyses
Adverse events analyses including the analysis of adverse events (AEs), Serious (SAEs)
and other significant AEs will be based on GSK Core Data Standards. The details of the 
planned displays are provided in Appendix 12: List of Data Displays.
An overview summary of AEs, including counts and percentages of subjects with any 
AE, AEs related to study treatment, AEs leading to permanent discontinuation of study 
treatment, AE leading to dose reductions, AEs leading to dose delays OR interruptions, 
SAEs, SAEs related to study treatment, fatal SAEs, and fatal SAEs related to study 
treatment will be produced.
A summary of non-serious AEs that occurred in strictly 5% of the subjects or above will 
be provided (no rounding for the percentage will be used in terms of 5% threshold, e.g., 
event with 4.9% incidence rate should not be included in this table). The summary will be 
displayed by SOC and PT.
The relationship between MedDRA SOC, PT, and Verbatim Text will be displayed.
Adverse events (AEs) will be graded according to the CTCAE, Version 4.0. Adverse 
events will be coded to the preferred term (PT) level using the Medical Dictionary for 
Regulatory Affairs (MedDRA dictionary). 
A summary of number and percentage of subjects with any adverse events by maximum 
grade will be produced. AEs will be sorted by Preferred term (PT) in descending order 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 adverse event will be counted only 
once at the maximum grade no matter how many events they have.
In addition, the frequency and percentage of AEs (all grades) will be summarized and 
displayed in two ways: 1) in descending order of total incidence by PT only and 2) in 
descending order of total incidence by System Organ Classes (SOC) and PT and 
Maximum Grade. In the SOC row, the number of subjects with multiple events under the 
same system organ class will be counted once.
A separate summary will be provided for study treatment-related AEs. A study treatment-
related AE is defined as an AE for which the investigator classifies the relationship to 
study treatment as “Yes”. A worst-case scenario approach will be taken to handle missing 
relatedness data, i.e. the summary table will include events with the relationship to study 


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treatment as ‘Yes’ or missing. The summary table will be displayed in descending order 
of total incidence by SOC and PT and Maximum Grade.
All AEs will be listed. Additionally, a listing of subject IDs for each individual AE will 
be produced. 
A listing of adverse events recorded as dose-limiting toxicities will be provided. 
Additionally, a summary of the number of patients experiencing DLT’s in each cohort 
will be provided.
The summary of adverse event by SOC and PT and maximum grade, and AE by PT will
also be produced for the following subgroups:
Prior anti-cancer therapy of interest: 

With prior Daratumumab Treatment and Refractory to Both Immunomodulators and 
Proteasome Inhibitors

Without prior Daratumumab Treatment

Refractory to Both Immunomodulators and Proteasome Inhibitors
8.2.
Adverse Events of Interest Analyses
There are no pre-defined Adverse Events of Special Interest in the protocol, as it was a 
first time in human (FTIH) trial. During the course of the study, the analyses of the 
following adverse events of interest were included upon the safety review team (SRT) 
requests.

Corneal events

Thrombocytopenia

Neutropenia

Hematologic Toxicity

Infusion-related Reactions as collected in the eCRF
For Corneal events, Thrombocytopenia, Neutropenia Hematologic Toxicity, a
comprehensive list of MedDRA terms based on clinical review will be used to identify 
each type of event. Changes to the MedDRA dictionary may occur between the start of 
the study and the time of reporting and/or emerging data from on-going studies may 
highlight additional adverse events of interest, therefore the list of terms to be used for 
each event of interest and the specific events of interest will be based on the SRT 
agreements in place at the time of reporting. The details of the planned displays are 
provided in Appendix 12: List of Data Displays.
Summaries of the number and percentage of subjects with these events will be provided 
for each type of events separately by preferred term and maximum grade. The time of 


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onset and duration of first occurrence of each type of events will be summarized using 
summary statistics mean, standard deviation, median, minimum value, and maximum. 
The number and percentage of subjects who have time of onset of first occurrence (1-21, 
22-42, 43-63, >63 days) will be reported. The number and percentage of subjects who 
have duration of first occurrence (1-21, 22-42, >42 days) will be reported.
The summary of event characteristics will also be provided, including number of subjects 
with any event, number of events, number of subjects with any event that is serious, 
number of subjects with any event that is related to study treatment, number of 
occurrences (One, Two, Three or more), maximum grade 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, 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.
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 time of death relative 
to the last dose of medication (>30 days or 30 days) and primary cause of death (disease 
under study, SAE related to study treatment, or other). A supportive listing will be 
generated to provide subject-specific details on subjects who died. 
All SAEs will be tabulated based on the number and percentage of subjects who 
experienced the event. Separate summaries will also be provided for study treatment-
related SAEs. The summary tables will be displayed in descending order of total 
incidence by SOC and PT.
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.
AEs of maximum grade of 3 or higher will be summarized separately by SOC and PT.


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8.4.
Adverse Events Leading to Discontinuation of Study 
Treatment and/or Withdrawal from the Study and Other 
Significant Adverse Events
The following categories of AEs will be summarized separately in descending order of 
total incidence by SOC and PT and separate supportive listings will be generated with 
subject level details for those subjects:

AEs Leading to Permanent Discontinuation of Study Treatment or Withdrawal from 
Study

AEs Leading to Discontinuation of Study Treatment

AEs Leading to Dose Interruptions or Delays

AEs Leadings to Dose Reductions
8.5.
Pregnancies 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be recorded 
as an AE or SAE as described in the protocol. If subjects and subjects’ partner become 
pregnant while on the study, the information will be included in the narratives and no 
separate table or listing will be produced.
8.6.
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 12: List of Data Displays.
Summary of change from baseline by scheduled visits using mean, median, standard 
deviation, minimum and maximum will be provided.
Summaries of worst case grade increase from baseline grade will be provided for all the 
lab tests that are gradable by CTCAE v4.0. These summaries will display the number and 
percentage of subjects with a maximum post-baseline grade increasing from their 
baseline grade. Any increase in grade from baseline will be summarized along with any 
increase to a maximum grade of 3 and any increase to a maximum grade of 4. Missing 
baseline grade will be assumed as grade 0. For laboratory tests that are graded for both 
low and high values, summaries will be done separately and labelled by direction, e.g., 
sodium will be summarized as hyponatremia and hypernatremia.
For lab tests that are not gradable by CTCAE v4.0, summaries of worst case changes 
from baseline with respect to normal range will be generated. Decreases to low, changes 
to normal or no changes from baseline, and increases to high will be summarized for the 
worst case post-baseline. If a subject has a decrease to low and an increase to high during 
the same time interval, then the subject is counted in both the “Decrease to Low” 
categories and the “Increase to High” categories. 


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Separate summary tables for hematology, and chemistry laboratory tests will be 
produced. Liver function laboratory tests will be included with chemical chemistry.
A supporting listing of laboratory data for subjects with abnormalities of potential clinical 
concern will be provided. A separate listing of laboratory data with character values will 
also be provided. For lab test values that can be graded, values of grade 1 or above are 
defined as values of potential clinical concern. For lab test values that can not be graded, 
values out of the normal range are defined as values of potential clinical concern.
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.
8.6.1.
Analyses of Liver Function Tests
Summaries of hepatobiliary laboratory events including possible Hy’s law cases will be 
provided in addition to what has been described above. 
A plot of maximum total bilirubin versus maximum ALT will be generated. Plots of 
maximum AST versus maximum LDH and maximum AST versus maximum Creatinine 
Kinase will be generated.
A Summary of Liver Monitoring/Stopping Event Reporting will be provided. The 
medical conditions data for subjects with liver stopping events will be listed. The 
substance use data for subjects with liver stopping events will be listed.  
8.7.
Other Safety Analyses
The analyses of non-laboratory safety test results including ECGs and vital signs will be 
based on GSK Core Data Standards, unless otherwise specified. The details of the 
planned displays are presented in Appendix 12: List of Data Displays.
Unless otherwise specified, the denominator in percentage calculation at each scheduled 
visit will be based on the number of subjects with non-missing value at each particular 
visit.
Performance Status
ECOG performance status will be summarized at baseline and each post-baseline 
scheduled visit. Summaries will use frequency and percentage of subjects at each planned 
assessment time. A summary of change from baseline by scheduled visits will be 
performed, as well as the worst case post-baseline and the best case post-baseline changes 
during the study (improved, no change, deteriorated).
A supporting listing will also be provided. 


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ECG
A summary of the number and percentage of subjects who had normal and abnormal 
(clinically significant and not clinically significant) ECG findings will be displayed by 
scheduled visits as well as for the worst case post-baseline. 
The QTc values based on Fridericia formula will be rounded to the integer and the values 
will be categorized into the following ranges: Grade 0 (<450), Grade 1 (450-480), Grade 
2 (481-500), and Grade 3 (≥501). Summaries of grade increase will be provided. These 
summaries will display the number and percentage of subjects with any grade increase, 
increase to grade 2 and increase to grade 3 in the worst case post-baseline only. 
The changes in QTc values will be categorized into the clinical concern ranges which are 
specific to changes in QTc: 31-60 and >60 msec. A summary of change in QTc value will 
display the number and percentage of subjects with a change within each range in the 
worst case post-baseline only. Subjects with missing baseline values will be excluded 
from this summary.
A listing of QTc values of potential clinical importance will be provided
The summaries and listing of QTc will use the collected values based on Fridericia 
formula.
A figure plotting the baseline QTc and the worst-case post-baseline values will be 
produced. The figure will have reference lines at 480 and 500 msec for both the ordinate 
and the abscissa axes. There will be diagonal reference lines at equality (i.e. a 45 degree 
line), at equality plus 30 msec, and at equality plus 60 msec.
LVEF
Absolute change from baseline in LVEF will be summarized in the worst case post-
baseline only. Only the post-baseline assessments that used the same method (ECHO or 
MUGA) 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


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LVEF results will also be listed with subject level details including absolute change from 
baseline.
Ocular Exams
For best corrected visual acuity (BCVA), if data is available, summary statistics for the 
logMAR score at baseline,  end of study treatment and last follow-up exam will be 
displayed separately by eye using mean, median, standard deviation, minimum and 
maximum. Changes of logMAR score from baseline to end of treatment visit, last follow-
up exam and maximum (worst) change from baseline will be summarized based on the 
following categories: no change/improved vision: a change from baseline <0.12; a 
possible worsened vision: a change from baseline >=0.12 to <0.3; a definite worsened 
vision: a change from baseline >=0.3. Subjects with character values of visual acuity 
exam results will not be included in this summary.
Number and percentage of subjects who experienced corneal clinical signs will be 
summarized. Among subjects who experienced corneal clinical signs, number and 
percentage of subjects with/without reported corneal events will be provided. If data is 
available, the summary will also be provided at end of study treatment visit and last 
follow-up exam. Visual acuity/ abnormal corneal exam results (eye level) at each visit, 
and incidence of corneal clinical signs and reported corneal events (subject level) during 
the study will be listed. The findings considered ‘corneal clinical signs’ were identified 
from the pre-defined list of choices in the eCRF. 
Listing of abnormal conjunctival exam results, listing of abnormal slit lamp Lens and slit 
lamp anterior chamber exam results and listing of indirect fundoscopic exam and intra-
ocular pressure results will be provided separately.
Constitutional Symptoms (or B-Symptoms)
A summary of the number and percentage of subjects with any constitutional symptom 
/B-symptom will be displayed by scheduled visits. A summary of improvement, i.e. 
number of subjects who had no symptoms at each post-baseline scheduled visit and had 
at least one at baseline, will also be provided. 
A supporting listing will be provided. 
Organ Examination
The number and percentage of subjects with normal or enlarged organs based on liver 
and spleen examination by palpation/CT scan will be summarized by scheduled visits.
A supporting listing will also be provided. 


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9.
PHARMACOKINETIC ANALYSES
The pharmacokinetic (PK) analyses will be based on the Pharmacokinetic population, 
unless otherwise specified.
Pharmacokinetic data from Part 1 of the study will be analyzed using standard non-
compartmental methods, and combined data from Part 1 and Part 2 of the study will be 
analyzed in a population approach using nonlinear mixed effects modeling. Full details 
are presented in Appendix 12: List of Data Displays. 
9.1.
Endpoint / Variables
9.1.1.
Drug Concentration Measures
Refer to Appendix 5: Data Display Standards & Handling Conventions (Section 16.5.3
Reporting Standards for Pharmacokinetic)
9.1.2.
Derived Pharmacokinetic Parameters
9.1.2.1.
Non-compartmental Analysis

The pharmacokinetic parameters for Part 1 will be calculated by standard non-
compartmental analysis according to current working practices and using Phoenix 
WinNonlin, version 6.3 or later.

All calculations of non-compartmental parameters will be based on actual sampling 
times.

Pharmacokinetic parameters described in Table 7 will be determined from the Cycle 1 
plasma concentration-time data in Part 1 of the study separately for each analyte, as 
data permit.
Table 7
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-)
Area under the concentration-time curve during the dosing interval
AUC(0-∞)
Area under the concentration-time curve extrapolated to infinity will be calculated as: 
AUC = AUC(0-t) + C(t) / lambda_z
%AUCex
The percentage of AUC (0-∞) obtained by extrapolation (%AUCex) will be calculated as:
[AUC(0-inf) – AUC(0-t)] / AUC(0-inf) x 100
Cmax
Maximum observed concentration, determined directly from the concentration-time data 
for each cycle.  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
C, 
Trough concentration prior to the next dose for each cycle


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Parameter
Parameter Description
Ctrough
t½
Apparent terminal half-life will be calculated as: 
t½ = ln2 / lambda_z
tlast
Time of last observed quantifiable concentration
CL
Clearance
Vss
Volume of distribution at steady state
z, 
lambda_z
Terminal phase rate constant
Ae(0-t)
Urinary recovery of cys-mcMMAF within t hours after start of infusion will be calculated 
as:
Urine cys-mcMMAF concentration x 24-h urine volume
t = time from start of infusion to end of urine collection period (24 h)
Fe(0-t)
Fraction of cys-mcMMAF dose excreted within t hours after start of infusion will be 
calculated as:
Ae(0-t) / cys-mcMMAF dose
9.2.
Population of Interest 
The primary pharmacokinetic analyses will be based on the “Pharmacokinetic” 
population, unless otherwise specified.
9.3.
Statistical Analyses / Methods
Details of the planned displays are provided in Appendix 12: List of Data Displays and 
will be based on GSK Data Standards and statistical principles. Unless otherwise 
specified, endpoints / variables defined in Section 9.1 will be summarised using 
descriptive statistics, graphically presented (where appropriate) and listed.
9.3.1.
Statistical Methodology Specification
The following pharmacokinetic statistical analyses will only be performed if sufficient 
data are available.
9.3.1.1.
Exploratory assessment of dose proportionality:
The PK-dose relationship initially will be examined graphically by plotting AUC(0-∞), 
AUC(0-), and Cmax as a function of the dose levels administered; AUC(0-t) may be 
used for cys-mcMMAF.  Plots of PK parameters versus dose will be produced, with two 
plots for each PK parameter. The first will be on a linear scale, and the second will use 
the logarithmic scale for both axes. 
In practice, at least three dose levels are required to assess dose proportionality. Hence, if 
more than two dose cohorts are required to reach MTD (or recommended dose based on 
available safety, PK, and response data), dose proportionality of GSK2857916, unbound 


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antibody, total antibody, and cys-mcMMAF following administration in Cycle 1 will be 
evaluated, if data permit, using the power model.
Dose Proportionality Analysis
Endpoint(s)

Loge-transformed single dose PK parameters listed below for each analyte will be investigated
for Cycle 1 Day 1 in Part 1 if data permit.
o
AUC(0-) or AUC(0-), Cmax, Ctrough for GSK2857916 (ADC), total antibody, 
unbound antibody
o
AUC(0-t), Cmax, Ctrough for cys-mcMMAF
Model Specification

Endpoints for each analyte will be separately analyzed using appropriate methods for 
GSK2857916 doses. 

Power Model

Dose proportionality of PK parameters defined above in Endpoints will be assessed 
following single dose administration of GSK2857916 between 0.03 mg/kg and 4.6 mg/kg, 
using the power model as described below:
               y = α * doseβ
               where y denotes the PK parameter being analyzed and α depends on subject.  

Dose proportionality implies that β=1 and will be assessed by estimating β along with its 
90% confidence interval. The exponent, β, in the power model will be estimated by 
regressing the loge-transformed PK parameter on loge-transformed dose.

The power model will be fitted by restricted maximum likelihood (REML) using SAS Proc 
Mixed. A power model with only subject as a random effect power model will be fitted. The 
mean slope will be estimated from the power model and the corresponding 90% 
confidence interval calculated. Model specification (e.g. random statement, variance 
structure) could be explored for achieving convergence.

If the 90% confidence interval for the slope regressing dose against exposure is contained 
within the interval (0.8, 1.25), the exposure will be considered to be dose proportional.
Model Checking & Diagnostics

Refer to Section 9.3.2.
Model Results Presentation

Power Model

The mean slope and the corresponding 90% confidence interval for each parameter will be 
produced in tabular format. 

Comparative plots of individual PK parameters will be generated by treatment on linear 
and semi-logarithmic scales.

Supportive SAS output from statistical analysis will be generated.
9.3.1.2.
Assessment of Accumulation Ratio:  
To assess the extent of accumulation following GSK2857916 repeat dosing, the observed 
accumulation ratio (Ro) for GSK2857916, total antibody, unbound antibody, and cys-
mcMMAF will be determined as ratio of concentration at end of infusion (CEOI) and 


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Ctrough at steady-state to CEOI and Ctrough after the first dose, respectively, adjusted 
for any change in GSK2857916 dose.
For the purpose of accumulation ratio analysis, CEOI at each cycle will be used.  
Preliminary analysis found that cys-mcMMAF Cmax did not occur at or near EOI in 
most cases; therefore, the cys-mcMMAF accumulation ratio based on CEOI is not based 
on Cmax.
Accumulation ration will only be derived and analyses will only be performed for 
subjects who received at least 80% of the planned dose at cycle 1.Ro(CEOI) = CEOI
CxD1/CEOI C1D1;
x = 3, 5;
Ro(Ctrough) = Ctrough CxD1/Ctrough C1D1;
x = 4;
Only one accumulation ratio for CEOI and Ctrough will be derived for each subject 
according to the rules below:
Preliminary pharmacokinetic data indicate that the pharmacokinetics for the third 
consecutive dose given at the planned interval will be at steady state.  Therefore, based 
on the study design, subjects who meet one of the following criteria will be at steady state
When assessing accumulation ratio based on CEOI:

Subjects who receive the same dose without delay or change for Cycles 1, 2, and 3 
(i.e., with dosing delays of ≤3 days).  In this case, Cycle 3 represents steady state.  
Accumulation ratios are calculated as Cycle 3/Cycle 1.  

Subjects who have a dose reduction or two by Cycle 3, but then dose is maintained at 
the same level and interval through Cycle 5.  Cycle 5 represents steady-state 
pharmacokinetics, but dose adjustment is needed.  Dose adjustment:  multiply CEOI
values by the ratio (starting dose level/Cycle 3-5 dose level).  Accumulation ratio = 
adjusted Cycle 5/Cycle 1.
When assessing accumulation ratio based on Ctrough:

Subjects who receive the same dose without delay or change to Cycle 4 (i.e., with 
dosing delays of ≤3 days).  Accumulation ratio = Cycle 4 Ctrough/Cycle 1 Ctrough.

Subjects who have a dose reduction by Cycle 2, but then dose is maintained at the 
same level and interval through Cycle 4.  Cycle 4 represents steady-state 
pharmacokinetics, but dose adjustment is needed.  Dose adjustment:  multiply 
Ctrough values by the ratio (starting dose level/Cycle 2-4 dose level).  Accumulation 
ratio = adjusted Cycle 4 Ctrough/Cycle 1 Ctrough.
Accumulation ratios of CEOI and Ctrough will be summarised using descriptive statistics
by planned initial dose level, graphically presented (where appropriate) and listed.


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9.3.1.3.
Assessment of Analyte Ratios: 
For the purpose of analyte ratio analysis, CEOI at each cycle will be used, and Ctrough is 
defined as the concentration immediately prior to the next cycle dose.  Preliminary 
analysis found that cys-mcMMAF Cmax did not occur at or near EOI in most cases; 
therefore, the cys-mcMMAF analyte ratio based on EOI is not based on Cmax.
Analyte Ratios of CEOI and Ctrough are defined as the ratio of CEOI and Ctrough for 
analytes: unbound antibody, total antibody, and cys-mcMMAF to CEOI and Ctrough for 
analyte ADC at each cycle:
Ratio of analytes at each cycle versus ADC at Cycle X:
Ra (CEOI) = CEOI (unbound antibody, total antibody, cys-mcMMAF) Cycle X
                                                     CEOI (ADC) Cycle X
X = 1, 2, 3, 5;
Ra (Ctrough) = Ctrough (unbound antibody, total antibody, cys-mcMMAF) Cycle X
                                                     Ctrough (ADC) Cycle X
X = 1, 2, 4;
To fit into the analysis model, the units of the analytes need to be converted from ng/mL 
or pg/mL to nM as below. 
Original unit
Operation
Converted unit
ADC
ng/mL
/152.1
nM
Total Antibody
ng/mL
/152.1
nM
Unbound Antibody
ng/mL
/152.1
nM
cys-mcMMAF
pg/mL
/1045
nM
Analyte ratios of CEOI and Ctrough for each will be summarised using descriptive 
statistics by planned initial dose level and cycle, graphically presented (where 
appropriate) and listed.


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9.3.2.
Model Checking & Diagnostics
Endpoint(s)

For Dose Proportionality Analysis (Part 1), Loge-transformed single dose PK 
parameters as defined in Section 9.3.1.1, as applicable.
Analysis

Mixed Effects
Assumptions:

Model assumptions will be applied, but appropriate adjustments may be made based on the 
data.

The Kenward and Roger method for approximating the denominator degrees of freedom and 
correcting for bias in the estimated variance-covariance of the fixed effects will be used.

An unstructured covariance structure for the G matrix will be used by specifying ‘type=UN’ on 
the RANDOM line.
o
In the event that this model fails to converge, alternative correlation structures may be 
considered such as VC or CS. 
o
Akaike's Information Criteria (AIC) will be used to assist with the selection of covariance 
structure.

Distributional assumptions underlying the model used for analysis will be examined by 
obtaining a normal probability plot of the residuals and a plot of the residuals versus the fitted 
values (i.e., checking the normality assumption and constant variance assumption of the model 
respectively) to gain confidence that the model assumptions are reasonable. 

If there are any departures from the distributional assumptions, alternative models will be 
explored using appropriate transformed data.


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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, data permitting.  The influence of subject demographics, baseline 
characteristics including disease activity, and other covariates on the pharmacokinetics of 
GSK2857916 will be investigated.  The individual subject pharmacokinetic parameters 
will be estimated and documented for the purposes of any subsequent exposure-response 
(PK/PD) analyses. This analysis will be performed by CPMS and reported separately. 
A summary of the planned population pharmacokinetic analyses is outlined below:

Plasma concentration-time data for GSK2857916 ADC will be subjected to 
nonlinear mixed effects modelling using the program NONMEM to develop a 
population pharmacokinetic model. A similar approach may be used on the data from 
two analytes (ADC and cys-mcMMAF) and three analytes (ADC, total antibody, and 
cys-mcMMAF) together.  

Individual post hoc estimated pharmacokinetic parameters will be summarized 
descriptively.

To support this analysis, a population PK dataset will be generated. The details for 
the dataset specifications are provided in Appendix 9: Population Pharmacokinetic 
(PopPK) Analyses.
Detailed population PK methodology is presented in Appendix 9: Population 
Pharmacokinetic (PopPK) Analyses.


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11.
PHARMACODYNAMIC (AND / OR BIOMARKER)
ANALYSES
The pharmacodynamic analyses will be documented in a separate RAP.


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12.
PHARMACOKINETIC / PHARMACODYNAMIC
ANALYSES
12.1.
Exposure-Response for Efficacy and Corneal Events
The primary goal of this analysis is to characterize the 
pharmacokinetic/pharmacodynamic relationships for GSK2857916 administered IV in 
subjects with multiple myeloma for efficacy and corneal events, data permitting.  In these 
analyses, drug plasma concentration (or pharmacokinetic parameter) data and 
pharmacodynamic data will be subjected to logistic regression and time-to-event analysis, 
as appropriate, using suitable software.  The influence of subject demographics and 
baseline characteristics, including disease activity, in this population may be investigated. 
Detailed PK/PD methodology is provided in Appendix 10:  Pharmacokinetic / 
Pharmacodynamic Analyses.  This analysis will be performed by CPMS and reported 
separately.
12.2.
Concentration-QTc Analyses
For each ECG assessment, the individual subject’s QTcF change from baseline will be 
calculated and will be merged with time-matched PK concentration values for the 
timepoints at which they are available. QTcF change from baseline (y-axis) will be 
plotted against the PK concentration data (x-axis) separately for each analyte (ADC, 
unbound mAb, total mAb, and cys-mc-MMAF).  If appropriate, linear regression 
analyses may be performed for each analyte-QTcF plot.


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13.
HEALTH OUTCOMES ANALYSES
Symptom impact and HRQoL will be assessed using the e-Diary. The Pain (average and 
worst) and Fatigue (worst) items will be scored as individual items. Baseline will be 
calculated for each item as the mean of all of the assessments captured in the period prior 
to Cycle 1 Day 1 (treatment start date) (patients can only start the diary 2 to 4 days prior 
to Cycle 1 Day 1). There will be no minimum number of data points required to calculate 
a baseline, if only one day has been completed in this time period then this will be used 
as Baseline value. 
Scores will be created for each pain (bone pain worst, bone pain average) and fatigue 
item (worst) during the treatment cycle. The mean for each item will be calculated from 
the available data for assessments on Day 1 through to Day 8 in each cycle (for a score to 
be calculated, at least 4 of the 8 days must be completed, otherwise data to be set to 
missing). For the assessment at Day 15 the stand-alone value will be the score for that 
item for that day. If not completed, then data for Day 15 is set to missing. Change from 
baseline for all pain and fatigue items will be assessed at each cycle. Change will be 
calculated for both time points (Day 1-Day 8 average and Day 15).
Visual Functioning Questionnaires (NEI VFQ-25 and OSDI): Data will be collected from 
end of treatment (EOT) visit as baseline. Additional data will be collected in follow-up 
visits on a monthly basis for subjects with ongoing corneal events or signs at EOT for 1 
year or until resolution, whichever occurs first. These data will not be collected for 
subjects who already completed the treatment. Due to limited number of on-treatment 
subjects at the time of protocol amendment, only individual subject data will be listed.
Data for both measures will be scored as outlined in the User Manuals. 
For the NEI VFQ-25 data will be presented for the overall composite score and the 11 
vison-targeted sub-scores: global vision rating, difficulty with near vision activities; 
difficulty with distance vision activities; limitations in social functioning due to vision; 
role limitations due to vision; dependency on others due to vision; mental health 
symptoms due to vision; driving difficulties; limitations with peripheral vision, 
limitations with color vision; and corneal pain. Items that are left blank (missing data) are 
not taken into account when calculating the scale scores. Sub-scales with at least one item 
answered can be used to generate a sub-scale score. Hence scores represent the average 
for all items in the sub-scale that the respondent answered. Only individual subject data 
will be listed.
For the OSDI, the total score will be calculated as well as scores for the subscales (ocular 
symptom, visual related function and environmental triggers). The total OSDI score 
= ([sum of scores for all questions answered × 100]/[total number of questions answered 
× 4]). Subscale scores are computed similarly with only the questions from each subscale 
used to generate its own score. Only individual subject data will be listed.


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14.
ANTI-DRUG ANTIBODY ANALYSES
For each subject, the results and titers of anti-GSK2857916 binding antibodies, and also 
ADC and total antibody concentration will be listed for each assessment time point. The 
frequency and percentage of subjects with positive and negative results will be 
summarized for each assessment time and overall for each subject by dose cohort. The 
conclusive results will be based on the total antibody concentration.


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15.
REFERENCES
Ahn EA, Karlsson MO, Dunne A, et al. Likelihood based approaches to handling data 
below the quantification limit using NONMEM VI. J. Pharmacokinet. Pharmacodyn. 
2008; 35:401-21.
Beal SL. Ways to fit a model with some data below the quantification limit. J. 
Pharmacokinet. Pharmacodyn. 2001; 28:481-504.
Brookmeyer R, Crowley J. A confidence interval for the median survival time. 
Biometrics. 1982 Mar 1:29-41.
GlaxoSmithKline Document Number 2012N155299_05, Study ID: BMA117159. A 
Phase I Open-label, Dose Escalation Study to Investigate the Safety, Pharmacokinetics, 
Pharmacodynamics, Immunogenicity and Clinical Activity of the Antibody Drug 
Conjugate GSK2857916 in Subjects with Relapsed/Refractory Multiple Myeloma and 
Other Advanced Hematologic Malignancies Expressing BCMA. 2017
Hing JP, Woolfrey SG, Greenslade D, Wright PMC. Analysis of toxicokinetic data using 
NONMEM: impact of quantification limit and replacement strategies for censored data. J. 
Pharmacokinet. Pharmacodyn.  2001; 28:465-79.
Hume R. Prediction of lean body mass from height and weight. Journal of clinical 
pathology. 1966 Jul 1;19(4):389-91.
Lee J, Liu D. A predictive probability design for phase II cancer clinical trials. Clinical 
Trials 2008;5:93-106.
Neuenschwander B, Branson M, Gsponer T. Critical aspects of the Bayesian approach to 
phase I cancer trials. Stat Med. 2008 Jun 15; 27(13):2420-39.


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16.
APPENDICES
16.1.
Appendix 1: Protocol Deviation Management and Definitions 
for Per Protocol Population
This study does not have per protocol population.


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16.2.
Appendix 2: Schedule of Activities
16.2.1.
Protocol Defined Schedule of Events
Please see Section 7.1 of Protocol (Version: GSK Document Number 2012N155299_05). 
Weekly Dosing Schedule (Dose Escalation) for Multiple Myeloma and Dose Expansion 
Weekly Dosing Schedule for Multiple Myeloma were not explored in this study.
Weekly dosing schedule was not explored.


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16.2.2.
Dose Escalation
16.2.2.1.
Every 3 Weeks Dosing Schedule for Multiple Myeloma
Time and Events Table for Full Study (Cycle = 21 days)
Study Assessments1
Screen2
Day 1 
C1
Day 2 
C1
Day 8 
C1
Day 15 
C1
Day 1 
C2
D1 of C3-C16
End of Study 
Treatment 
3-Month 
Off-study 
Follow-up
Informed Consent
X
Baseline Demographics
X
Medical History
X
Physical Exam
X
X
X
At the start of each cycle
X
Ocular Exam
X3
X4
At the start of each cycle4
X4
ECOG Performance Status
X
X
At the start of each cycle
X
Vital Signs (BP, HR, Body 
Temperature)
X
X5
X
X
X5
At the start of each cycle5
X
Weight and Height
X
Weight 
only
Weight 
only
Weight only - At the start of each cycle
Weight only
Hematology
X
X6
X
X
X
At the start of each cycle
X
Clinical chemistry
X
X6
X
X
X
X
At the start of each cycle
X
Urine Dipstick
X
X6
X
At the start of each cycle
X
INR, PTT 
X
X6
X
X
X
At the start of each cycle
HBV/HCV tests
X
CK-MB, Troponin 
X7
X7
X7
At the start of each cycle7
X7
BNP
X8
UPEP and urine 
Immunofixation
X
X
At the start of each cycle
SPEP and serum 
Immunofixation, Serum M-
protein Calculation
X
X
At the start of each cycle
Kappa, lambda free LC, FLC 
ratio
X
X
At the start of each cycle
24 hr urine protein and 
albumin
X
X
At the start of each cycle


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Time and Events Table for Full Study (Cycle = 21 days)
Study Assessments1
Screen2
Day 1 
C1
Day 2 
C1
Day 8 
C1
Day 15 
C1
Day 1 
C2
D1 of C3-C16
End of Study 
Treatment 
3-Month 
Off-study 
Follow-up
IgG, IgM, IgA
X
X
At the start of each cycle
CRP, beta2 microglobulin
X
X
At the start of each cycle
Pregnancy Test 
X9
At the start of cycles 59, 99, 139
X9
X10
Chest X-ray
X
12-lead ECG
X11
X11
X11
X11
X11
At the start of each cycle11
X11
LVEF and valves assessment 
(ECHO)
X12
At the start of cycles 412, 912
X12
Extramedullary plasmacytoma 
imaging 
X13
At the start of cycles 513, 913, 1313
X13
BM Aspirate (see below for each test required within procedure):
Disease assessment 
X14
At the time of Complete Response
BCMA assessment and 
PD (flow) 
X15
X15
FISH testing 
X16
BM biopsy for disease 
assessment and BCMA 
expression (IHC) 
X17
At the time of CR
(disease assessment only)
Serum (soluble BCMA)
X18
X18
X18
X18
X18
Predose at the start of each cycle
X18
Serum (cytokines/chemokines)
X19
X
X19
At predose and EOI on D1 of each cycle
X
Serum (anti-drug-antibodies)
X
X20
At the start of cycles 320, 620, 920, 1220 and 
1620
X
Plasma-cfDNA 
X
X 
Peripheral blood (flow for 
TBNK)
X15
X15
At the start of each cycle15
X15
Serial Pharmacokinetics 
(blood)
X21
X21
X21
X21
X21
C3D1 only21
X22
Urine PK
X23
X23
Day 1 of cycles 423, 723, 1023, 1323, 1623
Premedication if needed
X
X
At the start of each cycle
GSK2857916  administration
X24
X24
X24
Steroid eye drops
X25
X25
X25
Adverse Events
Continuous


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Time and Events Table for Full Study (Cycle = 21 days)
Study Assessments1
Screen2
Day 1 
C1
Day 2 
C1
Day 8 
C1
Day 15 
C1
Day 1 
C2
D1 of C3-C16
End of Study 
Treatment 
3-Month 
Off-study 
Follow-up
Concomitant Medications
X
Continuous
Survival Status
X26
Subsequent Treatment
X26
1.
Assessments scheduled on days of dosing should be done prior to drug administration, unless otherwise specified.  All other assessments can be 3 days of scheduled 
occurrence unless otherwise specified.
2.
All Screening assessments must be performed within 14 days prior to first dose unless otherwise specified. Informed Consent must be signed before any study-specific 
assessments are performed.
3.
Screening examination to include BCVA (best-corrected visual acuity), slit lamp examination (with special focus on cornea), intraocular pressure, and dilated fundoscopic 
examination may be performed within 21 days prior to first dose.
4.
On-study exams to include BCVA (best-corrected visual acuity) and slit lamp examination (with special focus on cornea); window for exams is up to 3 days prior to dosing.
5.
On initial (first infusion) dosing day, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +10 minutes and +30 minutes (5 min)  after SOI, EOI, and 1 
hour post EOI.  On subsequent dosing days, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +30 minutes after SOI, and EOI.  The Sentinel Subject 
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.
6.
If completed within 72 hrs prior to the first dose, this assessment need not be repeated on Day 1 of Cycle 1. Refer to Table 15 of the protocol for comprehensive list of lab 
tests.  
7.
Troponin will be measured at the local lab (troponin I or T) and a central lab (troponin I).  CK-MB at the local lab or if not possible by a central laboratory.
8.
BNP to be measured locally, or if not available by a central laboratory, at screening; if cardiac workup is required due to safety concerns during the study, BNP should be 
measured.  
9.
Perform only in women of child-bearing potential.  A serum pregnancy test should be performed at screening, and subsequent pregnancy tests may be either serum or urine; 
10. Final pregnancy test (serum or urine) must be performed in women of childbearing potential 60 days after last study treatment.
11. On dosing days, ECG to be performed in triplicate at predose (within 30 minutes prior to SOI) and EOI.  On days where ECG timepoints align with PK sampling 
timepoints, ECGs should be performed prior to PK samples being drawn (PK sample should be taken at the exact nominal time; refer to footnote 21).  At 
screening, on interim visits (C1D8 and C1D15) and End of Study obtain a single ECG measurement.
12. At Screening, LVEF may be performed within 30 days prior to first dose. All ECHOs indicated on dosing days may be performed up to 5 days before dosing. All ECHOs to be 
done locally and sent to GSK for central imaging storage.
13. May be performed up to 21 days prior to C1D1 as screening value.  Needs to be performed by the same method throughout the study as was done at baseline (i.e. if PET 
scan was used as baseline, subject needs to be followed by PET scans).  Selected target lesion needs to be measured and followed over time.
14. Samples from within 14 days prior to first dose are acceptable.
15. Sample(s) collected for analysis by central lab.  The same sample will be used for BCMA (flow) and PD during Screening. On D8 only postdose PD assessment will be 
performed


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16. 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.
17. Archival tissue from up to 60 days prior to study is acceptable 
18. A single sample for sBCMA will be collected at C1D8, C1D15 and at the End of Study visit. sBCMA samples will also be collected on  C1D1 at predose (within 30 minutes 
prior to SOI), at EOI (5 minutes) and on C1D2 24h post SOI.  On C2D1 sBCMA will be collected pre-dose (within 30 minutes prior to SOI) and at the EOI (5 minutes)
19. Collect cytokines at predose (within 30 minutes prior to SOI) and EOI (5 min) (even when infusion is interrupted or halted) to assess allergic reaction)
20. All ADA samples will be collected prior to each infusion
21. PK samples to be taken (in all subjects) for both GSK2857916 and cys-mcMMAF measurement: C1D1 at pre-dose (within 30 minutes prior to SOI), 0.5 h after the start of the 
infusion (SOI) (5 min), at the end of infusion (EOI) just before EOI), 1 h after EOI, 3 h after EOI (5 min), 8 h after EOI (15 min), 24h after EOI (1h) (Day 2); C1D8 1 
sample; C1D15 1 sample; C2D1, at pre-dose (within 30 minutes prior to SOI) and at the EOI (just before EOI); C3D1 at pre-dose (within 30 minutes prior to SOI) and at the 
EOI (just before EOI).
22. Collect 1 PK sample at each subject’s final visit. 
23. Pre-specified amounts of urine will be collected for PK analysis from the 24 hour urine collection at Screening, C2D1, C4D1, C7D1, C10D1, C13D1, and C16D1.  Refer to 
Section 7.4.2 of the protocol for details.
24. Study drug administration 3 day window only
25. Prophylaxis with prednisolone phosphate 1% or dexamethasone 0.1% 1 drop QID x 4 days starting 1 day prior to treatment
26. Record subject’s survival status and whether subsequent treatment for disease was given.  Subject does not need to come in for visit.
Abbreviations:
ADA = Antibody Drug Antibody; ALP = alkaline phosphatase; BCVA = best corrected visual acuity; BNP = B-type natriuretic peptide; C1D1 = Cycle 1 Day 1, etc.; cfDNA = 
Circulating free DNA; CK = creatinine kinase;  CRP = C-reactive protein; EM = extramedullary;  EOI = End of Infusion; FLC = free light chain; PD = Pharmacodynamics; PK = 
Pharmacokinetics; QID = 4 times a day; SOI = start of infusion; SPEP = serum protein electrophoresis; UPEP = urine protein electrophoresis


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16.2.2.2.
Weekly Dosing Schedule (Dose Escalation) for Multiple Myeloma
Time and Events Table for Full Study (Cycle = 28 days)
Study Assessments1
Screen2
Day 1 
C1
Day 2 
C1
Day 8 
C1
Day 15 
C1
Day 1 
C2
D1 of C3-C16
End of Study 
Treatment
3-Month Off-
study 
Follow-up
Informed Consent
X
Baseline Demographics
X
Medical History
X
Physical Exam
X
X
X
At the start of each cycle
X
Ocular Exam
X3
X4
At the start of each cycle4
X4
ECOG Performance Status
X
X
At the start of each cycle
X
Vital Signs (BP, HR, Body 
Temperature)
X
X5
X
X
X5
At the start of each cycle5
X
Weight and Height
X
Weight 
only
Weight 
only
Weight only - At the start of each cycle
Weight only
Hematology
X
X6
X
X
X
At the start of each cycle
X
Clinical Chemistry
X
X6
X
X
X
X
At the start of each cycle
X
Urine Dipstick
X
X6
X
At the start of each cycle
X
INR, PTT
X
X6
X
X
X
At the start of each cycle
HBV/HCV tests
X
CK-MB , Troponin 
X7
X7
X7
At the start of each cycle7
X7
BNP
X8
UPEP and urine 
Immunofixation
X
X
At the start of each cycle
SPEP and serum 
Immunofixation and Serum-
M protein Calculation
X
X
At the start of each cycle
Kappa, lambda free LC, 
FLC ratio
X
X
At the start of each cycle
24 hr urine protein and 
albumin
X
X
At the start of each cycle
IgG, IgM, IgA
X
X
At the start of each cycle
CRP, beta2 microglobulin
X
X
X
At the start of each cycle


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Time and Events Table for Full Study (Cycle = 28 days)
Study Assessments1
Screen2
Day 1 
C1
Day 2 
C1
Day 8 
C1
Day 15 
C1
Day 1 
C2
D1 of C3-C16
End of Study 
Treatment
3-Month Off-
study 
Follow-up
Pregnancy Test 
X9
At the start of cycles 59, 99, 139
X9
X10
Chest X-ray
X
12-lead ECG
X11
X11
X11
X11
X11
At the start of each cycle11
X11
LVEF and valves 
assessment (ECHO)
X12
At the start of cycles 412, 912
X12
Extramedullary 
Plasmacytoma Imaging
X13
At the start of cycles 513, 913, 1313
X13
BM Aspirate (see below for each test required within procedure):
Disease assessment 
X14
At the time of Complete Response
BCMA assessment and 
PD (flow) 
X15
X15, 17
FISH testing 
X16
BM biopsy for disease 
assessment 
X18
At the time of Complete Response 
(disease assessment only)
Serum (soluble BCMA)
X19
X19
X19
X19
X19
Predose at the start of each cycle
X
Serum 
(cytokines/chemokines)
X20
X
X20
X20
X20
At predose and EOI on D1 of each cycle
X
Serum (anti-drug-
antibodies)
X21
X21
X21
At the start of cycles 321, 621, 921, 1221 and 
1621
X
Plasma-cfDNA
X
X
Peripheral blood (flow for 
TBNK and intracellular 
cytokine testing)
X15
X15
X15
At the start of each cycle15
X15
Serial Pharmacokinetics 
(blood)
X22
X22
X22
X22
X22
C3D1 only22
X23
Urine PK
X24
X24
Day 1 of cycles 424, 724, 1024, 1324, 1624
Premedication if needed
X
X
X
X
Each dosing week
GSK2857916 
administration
X25
X25
X25
X25
Each dosing week25
Steroid eye drops
X26
X26
X26
X26
Each dosing week26
Adverse Events
Continuous


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Time and Events Table for Full Study (Cycle = 28 days)
Study Assessments1
Screen2
Day 1 
C1
Day 2 
C1
Day 8 
C1
Day 15 
C1
Day 1 
C2
D1 of C3-C16
End of Study 
Treatment
3-Month Off-
study 
Follow-up
Concomitant Medications
X
Continuous
Survival Status
X27
Subsequent Treatment
X27
1.
Assessments scheduled on days of dosing should be done prior to drug administration, unless otherwise specified.  All other assessments can be done 3 days unless otherwise 
specified.
2.
All Screening assessments must be performed within 14 days prior to first dose unless otherwise specified.  Informed Consent must be signed before any study-specific
assessments are performed.
3.
Screening examination to include BCVA (best-corrected visual acuity), slit lamp examination (with special focus on cornea), intraocular pressure, dilated fundoscopic examination 
may be performed within 21 days prior to first dose
4.
On-study exams, to include BCVA (best-corrected visual acuity) and slit lamp examination (with special focus on cornea); window for exams is up to 3 days prior to dosing.
5.
On initial (first infusion) dosing day, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +10 minutes and +30 minutes (5 min) after SOI, EOI, and 1 hour 
post EOI.  On subsequent dosing days, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +30 minutes after SOI, and EOI.  On days where vital sign 
time points align with PK sampling timepoints, vital signs should be assessed prior to PK samples being drawn.  
6.
If completed within 72 hours prior to first dose, this assessment need not be repeated on Day 1 of Cycle 1.  Refer to Table 15 of the protocol for comprehensive list of lab tests.
7.
Troponin will be measured at the local (troponin I or T) and central (troponin I) lab.  CK-MB at the local lab or if not available by a central laboratory. 
8.
BNP to be measured locally, or if not available by a central laboratory, at screening; if cardiac workup is required due to safety concerns during the study, BNP should be 
measured.
9.
Perform only in women of child-bearing potential.  A serum pregnancy test should be performed at screening, and subsequent pregnancy tests may be either serum or urine.  
10. Final pregnancy test (serum or urine) must be performed in women of childbearing potential 60 days after last study treatment.
11. On dosing days, ECG to be performed in triplicate at predose (within 30 minutes prior to SOI) and EOI.  On days where ECG timepoints align with PK sampling timepoints, 
ECGs should be performed prior to PK samples being drawn (PK sample should be taken at the exact nominal time; refer to footnote 22).  At screening and at End of Study, 
obtain a single ECG measurement.
12. At Screening, LVEF may be performed within 30 days prior to first dose; All ECHOs indicated on dosing days may be performed up to 5 days before dosing.  ECHOs to be done 
locally and sent to GSK for central imaging storage.
13. May be performed up to 21 days prior to C1D1 as screening value.  Needs to be performed by the same method throughout the study as was done at baseline (i.e. if PET scan 
was used as baseline, subject needs to be followed by PET scans).  Selected target lesion needs to be measured and followed over time.
14. Samples from within 14 days prior to first dose are acceptable.
15. Sample(s) collected for analysis by central lab. The same sample collected on Day 1 of cycle 1 prior to dosing will be used for BCMA (flow) and PD u. 
16. 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.
17. Collect sample prior to dosing.


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18. Archival tissue from up to 60 days prior to study is acceptable.
19. A single sample for sBCMA will be collected at C1D8 predose, and at the End of Study visit. sBCMA samples will also  be collected on C1D1 at predose (within 30 minutes prior to 
SOI), at EOI (5 minutes) and on C1D2 24h post SOI. On C1D15 and C2D1 collect at predose (within 30 minutes prior to SOI) and EOI (5 minutes)
20. Collect cytokines at predose (within 30 minutes prior to SOI) and EOI (5 min) (even when infusion is interrupted or halted) to assess allergic reaction
21. All ADA samples will be collected prior to each infusion
22. PK samples to be taken (in all subjects) for both GSK2857916 and cys-mcMMAF measurement: C1D1 at predose (within 30 minutes prior to SOI), 0.5 h after the start of the 
infusion, at EOI (just before EOI), 1 h after EOI (5 min), 3 h after EOI (5 min), 8 h after EOI (15 min), and 24h after EOI (1 h) (Day 2); C1D8 at predose (within 30 minutes 
prior to SOI), and at EOI (just before EOI); C1D15 at predose (within 30 minutes prior to SOI) and at EOI (just before EOI); C2D1 at predose (within 30 minutes prior to SOI), at 
EOI (just before EOI); C3D1 at predose (within 30 minutes prior to SOI) and at EOI (just before EOI).
23. Collect 1 PK sample at each subject’s final visit.
24. Pre-specified amounts of urine will be collected for PK analysis from the 24 hour urine collection at Screening, C2D1, C4D1, C7D1, C10D1, C13D1, and C16D1.  Refer to Section 
7.4.2 of the protocol for details.
25. Study drug administration 1 day window only.
26. Prophylaxis with prednisolone phosphate 1% or dexamethasone 0.1% 1 drop QID x 4 days starting 1 day prior to treatment
27. Record subject’s survival status and whether subsequent treatment for disease was given.  Subject does not need to come in for visit.
Abbreviations:
ADA = Antibody Drug Antibody; ALP = alkaline phosphatase; BCVA = best corrected visual acuity; BNP = B-type natriuretic peptide; C1D1 = Cycle 1 Day 1, etc.; cfDNA = Circulating 
free DNA; CK = creatinine kinase;  CRP = C-reactive protein; EM = extramedullary;  EOI = End of Infusion; FLC = free light chain; PD = Pharmacodynamics; PK = Pharmacokinetics; 
QID = 4 times a day; SOI = start of infusion; SPEP = serum protein electrophoresis; UPEP = urine protein electrophoresis


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16.2.3.
Dose Expansion
16.2.3.1.
Every 3 Weeks Dosing Schedule for Multiple Myeloma
Time and Events Table for Full Study (Cycle = 21 days)
Study Assessments1
Screen2
Day 1 
C1
Day 8 
C1
Day 15 
C1
Day 1 C2
D1 of C3-C16
End of 
Study 
Treatment34
Monthly 
Follow 
up35
Baseline Demographics
X
Medical History
X
Physical Exam
X
X
X
At the start of each cycle
X
Ocular Exam
X3
X4
At the start of each cycle4
X4
X35
ECOG Performance 
Status
X
X
At the start of each cycle
X
Vital Signs (BP, HR, 
Body Temperature)
X
X5
X
X
X5
At the start of each cycle5
X
Weight and Height
X
Weight 
only
Weight only
Weight only - At the start of each 
cycle
Weight only
Hematology
X
X6
X
X
X
At the start of each cycle
X
Clinical chemistry
X
X6
X
X
X
At the start of each cycle
X
Urine Dipstick
X
X6
X
At the start of each cycle
X
INR, PTT
X
X6
X
X
X
At the start of each cycle
HBV/HCV tests
X
CK-MB , Troponin
X7,8
X7,8
X7,8
At the start of each cycle7, 8
X7,8
BNP
X9
UPEP and urine 
Immunofixation
X
X
At the start of each cycle
SPEP and serum 
immunofixation and 
Serum M-protein 
Calculation
X
X
At the start of each cycle
Kappa, lambda free LC, 
FLC ratio
X
X
At the start of each cycle


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Time and Events Table for Full Study (Cycle = 21 days)
Study Assessments1
Screen2
Day 1 
C1
Day 8 
C1
Day 15 
C1
Day 1 C2
D1 of C3-C16
End of 
Study 
Treatment34
Monthly 
Follow 
up35
24 hr urine protein and 
albumin
X
X
At the start of each cycle
IgG, IgM, IgA
X
X
At the start of each cycle
CRP, beta2 
microglobulin
X
X
At the start of each cycle
Pregnancy Test
X10
At the start of cycles 510, 910, 1310
X10
X11
Chest X-ray
X
12-lead ECG
X12
X12
X12
X12
X12
At the start of each cycle12
X12
LVEF and valves 
assessment (ECHO)
X13
At the start of cycles 413, 913
X13
Extramedullary 
Plasmacytoma Imaging
X14
At the start of cycles 514, 914, 1314
X14
BM Aspirate (see below for each test required within procedure):
Disease 
assessment
X15
At the time of Complete Response
BCMA assessment 
and PD (flow)
X16
X16, 18
FISH testing
X17
BM biopsy for disease 
assessment 
X19
At the time of CR (disease 
assessment only)
Serum (soluble BCMA)
X20
X20
Predose at the start of each cycle
X
Serum 
(cytokines/chemokines)
X21
X21
Predose and EOI on D1 of each 
cycle
X
Serum (anti-drug-
antibodies)
X22
X22
At the start of cycles 322, 622, 922, 
1222 and 1622
X
Plasma-cfDNA
X
X
Peripheral blood (flow 
for TBNK and 
intracellular cytokine 
testing)
X23
X
X23
At the start of each cycle23
X23
Sparse PK (blood)
X24
X24
C3D124 and C5D124 only
X25
Genetics sample
X26


CONFIDENTIAL
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Time and Events Table for Full Study (Cycle = 21 days)
Study Assessments1
Screen2
Day 1 
C1
Day 8 
C1
Day 15 
C1
Day 1 C2
D1 of C3-C16
End of 
Study 
Treatment34
Monthly 
Follow 
up35
Premedication if 
needed
X
X
X
GSK2857916  
administration
X27
X27
X27
Steroid eye drops
X28
X28
X28
Adverse Events
Continuous
Concomitant 
Medications
X
Continuous
e-Diary
X
X
X
X
X30
X30
X
OSDI
X31
X31
NEI-VFQ-25
X31
X31
Exit Interview
X32
Follow-up Interview
X33
Survival Status
X29
Subsequent Treatment
X29
1.
Assessments scheduled on days of dosing should be done prior to drug administration, unless otherwise specified.  All other assessments can be done 3 days unless otherwise 
specified
2.
All Screening assessments must be performed within 14 days prior to first dose unless otherwise specified. Informed Consent must be signed before any study-specific 
assessments are performed.
3.
Screening examination to include BCVA (best-corrected visual acuity), slit lamp examination (with special focus on cornea), intraocular pressure, and dilated fundoscopic 
examination may be performed within 21 days prior to first dose.
4.
On-study exams, to include BCVA (best-corrected visual acuity) and slit lamp examination (with special focus on cornea); window for exams is up to 3 days prior to dosing. In the 
event that a subject has a dose delay due to a non-ocular toxicity and an ocular exam has been performed for that cycle, a repeat ocular exam 3 days prior to dosing may be 
omitted if the participant did not have corneal signs on the previous exam and does not have any new corneal symptoms.
5.
On initial (first infusion) dosing day, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +10 minutes, +30 minutes (15 min) after SOI, EOI, and 1 hour post 
EOI.  On subsequent dosing days, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +30 minutes after SOI, and EOI.  On days where vital sign 
timepoints align with PK sampling timepoints, vital signs should be assessed prior to PK samples being drawn.  
6.
If completed within 72 hrs prior to the first dose, this assessment need not be repeated on Day 1 of Cycle 1.  Refer to Table 15 of the protocol for a comprehensive list of lab tests.  
7.
Troponin will be measured at the local (troponin I or T) and central (troponin I) lab.  
8.
CK-MB at the local lab or if not available by a central laboratory. 
9.
BNP to be measured locally, or if not available by a central laboratory, at screening; if cardiac workup is required due to safety concerns during the study, BNP should be 
measured.


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74
10. Perform only in women of child-bearing potential.  A serum pregnancy test should be performed at screening, and subsequent pregnancy tests may be either serum or urine.
11. Final pregnancy test (serum or urine) must be performed in women of childbearing potential 60 days after last study treatment.
12. ECGs to be performed in triplicate.  On dosing days, ECG to be performed at predose (within 30 minutes prior to SOI) and EOI.  At screening, on interim visits (C1D8 and C1D15) 
and End of Study, obtain a single ECG measurement. On days where ECG timepoints align with PK sampling timepoints, ECGs should be performed prior to PK samples 
being drawn (PK sample should be taken at the exact nominal time; refer to footnote 24) 
13. At Screening, LVEF may be performed within 30 days prior to first dose. All ECHOs indicated on dosing days may be performed up to 5 days before dosing. ECHOs to be done 
locally and sent to GSK for central imaging storage.
14. May be performed up to 21 days prior to C1D1 as screening value.  Needs to be performed with the same method throughout the study as was done at baseline (i.e. if PET scan 
was used as baseline, subject needs to be followed by PET scans).  Selected target lesion needs to be measured and followed over time.
15. Samples from within 14 days prior to first dose are acceptable.
16. Sample(s) collected for analysis at central lab. The same sample will be used for BCMA (flow) and PD. On D8 only postdose PD assessment will be performed, if applicable (refer 
to footnote 18).
17. 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.
18. Additional samples may be collected in some subjects (up to 6) for further exploration of PD.
19. Archival tissue from up to 60 days prior to study is acceptable.
20. Collect sBCMA at C1D1 predose (within 30 minutes prior to SOI) and at EOI (5 minutes), C2D1 at predose (within 30 minutes prior to SOI) and at EOI (+- 5 minutes).
21. Collect cytokines at predose (within 30 minutes prior to SOI) and EOI (5 min) (even when infusion is interrupted or halted) to assess allergic reaction
22. All ADA samples will be collected prior to each infusion
23. Flow cytometry performed central laboratory.
24. PK samples to be taken for both GSK2587916 and cys-mcMMAF measurement on C1D1, C2D1, C3D1, and C5D1 at predose (within 30 minutes prior to SOI) and at EOI (just 
before EOI).
25. Collect 1 PK sample at each subject’s final visit.
26. Informed consent for optional genetics research should be obtained before collecting a sample.
27. Study drug administration 3 day window only.
28. Prophylaxis with prednisolone phosphate 1% or dexamethasone 0.1% 1 drop QID x 4 days starting 1 day prior to treatment
29. All participants should be followed for survival for 1 year from last subject last dose. and whether subsequent treatment for disease was given.  Subject does not need to come in 
for visit. Participants who have completed treatment or the 3 month follow up visit (end of study) prior to amendment 5 will be reconsented for further follow up and survival status. 
30. e-Diary  to be completed at screening, then Days 1-7, 8, 15 of each treatment cycle. Upon implementation of the e-Diary, these assessments will be required.
31. OSDI and NEI-VFQ-25 to be administered during end of study treatment visit.  Additional assessments for subjects who are experiencing corneal symptoms to be completed via 
telephone on a monthly basis for up to 1 year, or until resolution of symptoms (whichever comes first) during the follow-up period. 
32. Exit interview to be performed within 21 days of end of study visit
33. Optional follow-up telephone interview to explore visual symptoms and changes in symptoms and related impacts following treatment discontinuation be performed at least 6 
months following the End of Study Treatment visit.  This interview would only be for those subjects who experienced corneal symptoms during treatment and consent to 
participate.
34. End of treatment visit should be performed within 30 days (+7 days) after the last dose or prior to the start of new anti-cancer treatment, whichever is earlier. In cases where more 
than 30 days (+7 days) have elapsed from the date of the subject’s last dose due to dosing delays and a subsequent decision to take the subject off treatment, the end of study 
treatment visit should be scheduled as soon as possible to allow the final assessments to be performed at the earliest date.


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35. Participants with corneal signs or symptoms at the end of study treatment visit should be monitored by ophthalmic exam once a  month after the last study dose until deemed 
clinically stable by an eye care professional complete resolution or for 12 months (whichever comes first). Corneal exams to include BCVA and slit lamp examination (with special 
focus on cornea). Participants who have completed treatment or the 3 month follow up visit (end of study) will be reconsented for  additional ophthalmology follow up.
Abbreviations:
ADA = Antibody Drug Antibody; ALP = alkaline phosphatase; BCVA = best corrected visual acuity; BNP = B-type natriuretic peptide; C1D1 = Cycle 1 Day 1, etc.; cfDNA = 
Circulating free DNA; CK = creatinine kinase;  CRP = C-reactive protein; EM = extramedullary;  EOI = End of Infusion; FLC = free light chain; PD = Pharmacodynamics; PK = 
Pharmacokinetics; QID = 4 times a day; SOI = start of infusion; SPEP = serum protein electrophoresis; UPEP = urine protein electrophoresis


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16.2.3.2.
Dose Expansion Weekly Dosing Schedule for Multiple Myeloma
Time and Events Table for Full Study (Cycle = 28 days)
Study Assessments1
Screen2
Day 1 
C1
Day 8 C1
Day 15 
C1
Day 1 
C2
Day 15 
C2
D1 of C3-C16
End of Study 
Treatment
3-Month 
Off-study 
Follow-up
Informed Consent
X
Baseline Demographics
X
Medical History
X
Physical Exam
X
X
X
At the start of each cycle
X
Ocular Exam
X3
X4
At the start of each cycle4
X4
ECOG Performance 
Status
X
X
At the start of each cycle
X
Vital Signs (BP, HR, Body 
Temperature)
X
X5
X5
X5
X5
At the start of each cycle5
X
Weight and Height
X
Weight 
only
Weight 
only
Weight only - At the start of each cycle
Weight
Hematology
X
X6
X
X
X
At the start of each cycle
X
Clinical chemistry
X
X6
X
X
X
X
At the start of each cycle
X
Urine Dipstick
X
X6
X
At the start of each cycle
X
INR, PTT 
X
X6
X
X
X
At the start of each cycle
HBV/HCV tests
X
CK-MB , Troponin 
X7
X7
X7
At the start of each cycle7
X7
BNP
X8
UPEP and urine 
immunofixation
X
X
At the start of each cycle
SPEP and serum 
immunofixation and Serum 
M-protein Calculation
X
X
At the start of each cycle
Kappa, lambda free LC, 
FLC ratio
X
X
At the start of each cycle
24 hr urine protein and 
albumin 
X
X
At the start of each cycle
IgG, IgM, IgA
X
X
At the start of each cycle


CONFIDENTIAL
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Time and Events Table for Full Study (Cycle = 28 days)
Study Assessments1
Screen2
Day 1 
C1
Day 8 C1
Day 15 
C1
Day 1 
C2
Day 15 
C2
D1 of C3-C16
End of Study 
Treatment
3-Month 
Off-study 
Follow-up
CRP, beta2 microglobulin
X
X
X
At the start of each cycle
Pregnancy Test 
X9
At the start of cycles 59, 99, 139
X9
X10
Chest X-ray
X
12-lead ECG
X11
X11
X11
X11
X11
At the start of each cycle11
X11
LVEF and valves 
assessment (ECHO)
X12
At the start of cycles 412, 912
X12
Extramedullary 
Plasmacytoma Imaging
X13
At the start of cycles 513, 913, 1313
X13
BM Aspirate (see below for each test required within procedure):
Disease assessment 
X14
At the time of Complete Response
BCMA assessment 
and PD (flow)
X15
X15, 17
FISH testing 
X16
BM biopsy for disease 
assessment 
X18
At the time of Complete Response (disease 
assessment only)
Serum (soluble BCMA) 
X19
X19
X19
X19
Predose at the start of each cycle
X
Serum 
(cytokines/chemokines)
X20
X20
X20
X20
Predose and EOI on D1 of each cycle
X
Serum (anti-drug-
antibodies)
X21
X21
X21
At the start of cycles 321, 621, 921, 1221 and 
1621
X
Plasma-cfDNA 
X
X
X 
Peripheral blood (flow for 
TBNK and intracellular 
cytokine testing)
X15
X
X15
At the start of each cycle15
X15
Sparse PK (blood) 
X22
X22
X22
X22
X22
C3D122, C3D1522, and C5D122 only
X23
Genetics sample
X24
Premedication if needed
X
X
X
X
X
Each dosing week
GSK2857916  
administration
X25
X25
X25
X25
X25
Each dosing week25
Steroid eye drops
X26
X26
X26
X26
X26
Each dosing week26
Adverse Events
Continuous


CONFIDENTIAL
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Time and Events Table for Full Study (Cycle = 28 days)
Study Assessments1
Screen2
Day 1 
C1
Day 8 C1
Day 15 
C1
Day 1 
C2
Day 15 
C2
D1 of C3-C16
End of Study 
Treatment
3-Month 
Off-study 
Follow-up
Concomitant Medications
X
Continuous
e-Diary
X
X
X
X
X
X28
X
Exit Interview
X29
Survival Status
X27
Subsequent Treatment
X27
1.
Assessments scheduled on days of dosing should be done prior to drug administration, unless otherwise specified. All other assessments can be done 3 days unless otherwise 
specified 
2.
All Screening assessments must be performed within 14 days prior to first dose unless otherwise specified. Informed Consent must be signed before any study-specific 
assessments are performed.
3.
Screening examination to include BCVA (best-corrected visual acuity), slit lamp examination (with special focus on cornea), intraocular pressure, and dilated fundoscopic 
examination may be performed within 21 days prior to first dose.
4.
On-study exams, to include BCVA (best-corrected visual acuity) and slit lamp examination (with special focus on cornea); window for exams is up to 3 days prior to dosing.
5.
On initial (first infusion) dosing day, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +10 minutes and +30 minutes (5 min) after SOI, EOI, and 1 hour 
post EOI.  On subsequent dosing days, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +30 minutes after SOI, and EOI.  On days where vital sign 
timepoints align with PK sampling timepoints, vital signs should be assessed prior to PK samples being drawn.  
6.
If completed within 72 hrs prior to the first dose, this assessment need not be repeated on Day 1 of Cycle 1.  Refer to Table 15 of the protocol for comprehensive list of lab tests.   
7.
Troponin will be measured at the local (troponin I or T) and central (troponin I) lab.  CK-MB at the local lab, or if not available by a central laboratory. 
8.
BNP to be measured locally, or if not available by a central laboratory, at screening; if cardiac workup is required due to safety concerns during the study, BNP should be 
measured.
9.
Perform only in women of child-bearing potential.  A serum pregnancy test should be performed at screening, and subsequent pregnancy tests may be either serum or urine
10. Final pregnancy test (serum or urine) must be performed in women of childbearing potential 60 days after last study treatment.
11. ECGs to be performed in triplicate.  On dosing days, ECG to be performed at predose (within 30 minutes prior to SOI) and EOI.  On days where ECG timepoints align with PK 
sampling timepoints, ECGs should be performed prior to PK samples being drawn (PK sample should be taken at the exact nominal time; refer to footnote 22). At 
screening and End of Study, obtain a single ECG measurement.
12. At Screening, LVEF may be performed within 30 days prior to first dose.  All ECHOs indicated on dosing days may be performed up to 7 days before dosing. ECHOs to be done 
locally and sent to GSK for central imaging storage.
13. May be performed up to 21 days prior to C1D1 as screening value.  Needs to be performed with the same method throughout the study as was done at baseline (i.e. if PET scan 
was used as baseline, subject needs to be followed by PET scans).  Selected target lesion needs to be measured and followed over time.
14. Samples from within 14 days prior to first dose are acceptable.
15. Sample(s) collected for analysis at central lab. The same sample collected on Day 1 of cycle1 prior to dosing will be used for BCMA (flow) and PD (refer to footnote 17).


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16. 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.
17. Additional samples may be collected from 6 subjects in the MM cohort.  Collect sample prior to dosing.
18. Archival tissue from up to 60 days prior to study is acceptable
19. A single sBCMA sample will be collected at C1D1 predose (within 30 minutes prior to SOI) unless otherwise specified.  On C1D15 and C2D1 collect samples at predose (within 30 
minutes prior to SOI) and at EOI (5 minutes).  
20. Collect cytokines at predose (within 30 minutes prior to SOI) and EOI (5 min) (even when infusion is interrupted or halted) to assess allergic reaction
21. All ADA samples will be collected prior to each infusion
22. PK samples to be taken for both GSK2857916 and cys-mcMMAF measurement at C1D1 predose (within 30 minutes prior to SOI), EOI (just before EOI), 1 hour post EOI (5 min), 
and 3 hours post EOI (5 min); predose (within 30 minutes prior to SOI) and EOI (just before EOI) on C1D8, C1D15, C2D1, C2D15, C3D1, C3D15, and C5D1
23. Collect 1 PK sample at each subject’s final visit
24. Informed consent for optional genetics research should be obtained before collecting a sample.
25. Study drug administration 1 day window only
26. Prophylaxis with prednisolone phosphate 1% or dexamethasone 0.1% 1 drop QID x 4 days starting 1 day prior to treatment
27. Record subject’s survival status and whether subsequent treatment for disease was given.  Subject does not need to come in for visit.
28. e-Diary  to be completed at screening, then Days 1-7, 8, 15 of each treatment cycle. Upon implementation of the e-Diary, these assessments will be required.
29. 29.Exit interview to be performed within 14 days of end of study visit
Abbreviations:
ADA = Antibody Drug Antibody; ALP = alkaline phosphatase; BCVA = best corrected visual acuity; BNP = B-type natriuretic peptide; C1D1 = Cycle 1 Day 1, etc.; cfDNA = 
Circulating free DNA; CK = creatinine kinase;  CRP = C-reactive protein; EM = extramedullary;  EOI = End of Infusion; FLC = free light chain; PD = Pharmacodynamics; PK = 
Pharmacokinetics; QID = 4 times a day; SOI = start of infusion; SPEP = serum protein electrophoresis; UPEP = urine protein electrophoresis


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16.2.3.3.
Dose Expansion Every 3 Weeks Dosing Schedule for Lymphomas
Study Assessments1
Screen2
Day 1 C1
Day 8 C1
Day 15 C1
Day 1 C2
D1 of C3-C16
End of 
Study 
Treatment26
Monthly 
Follow 
up27
Informed Consent
X
Baseline Demographics
X
Medical History
X
Physical Exam
X
X
X
At the start of each cycle
X
Ocular Exam
X3
X4
At the start of each cycle4
X4
X27
ECOG Performance 
Status
X
X
At the start of each cycle
X
Vital Signs (BP, HR, 
Body Temperature)
X
X5
X
X
X5
At the start of each cycle5
X
Weight and Height
X
Weight only
Weight only
Weight only - At the start of each 
cycle
Weight only
Hematology
X
X6
X
X
X
At the start of each cycle
X
Clinical chemistry
X
X6
X
X
X
At the start of each cycle
X
Urine Dipstick
X
X6
X
At the start of each cycle
X
INR, PTT
X
X6
X
X
X
At the start of each cycle
HBV/HCV tests
X
CK-MB, Troponin 
X7,8
X7,8
X7,8
At the start of each cycle7
X7,8
BNP
X9
24 hr urine protein and 
albumin 
X
X
At the start of each cycle
IgG, IgM, IgA
X
X
At the start of each cycle
CRP, beta2 
microglobulin
X
X
At the start of each cycle
Pregnancy Test 
X10
At the start of cycles 510, 910, 
1310
X10
X11
Chest X-ray
X
12-lead ECG
X12
X12
X12
X12
X12
At the start of each cycle12
X12
LVEF and valves 
assessment (ECHO)
X13
At the start of cycles 413, 913
X13
Serum (soluble BCMA) 
X14
X14


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Study Assessments1
Screen2
Day 1 C1
Day 8 C1
Day 15 C1
Day 1 C2
D1 of C3-C16
End of 
Study 
Treatment26
Monthly 
Follow 
up27
Serum 
(cytokines/chemokines)
X15
X15
Predose and EOI on D1 of each 
cycle
X
Serum (anti-drug-
antibodies)
X16
X16
At the start of cycles 316, 616, 916, 
1216 and 1616
X
Plasma-cfDNA 
X
X 
Peripheral blood (flow 
for TBNK and 
intracellular cytokine 
testing)
X17
X17
X17
At the start of each cycle17
X17
Sparse PK (blood)
X18
X18
C3D118 and C5D118
X19
Genetics sample
X20
CT Scan/PET Scan for 
disease assessments 
X21
At the start of cycles 4, 7, 10, 13, 
and 16
Premedication if needed
X
X
At the start of each cycle
GSK2857916  
administration
X22
X22
X22
Steroid eye drops
X23
X23
At the start of each cycle23
Tumor biopsy for BCMA 
expression
X24
Adverse Events
Continuous
Concomitant 
Medications
X
Continuous
Survival Status
X25
Subsequent Treatment
X25
1.
Assessments scheduled on days of dosing should be done prior to drug administration, unless otherwise specified.  All other assessments can be done 3 days of scheduled 
occurrence unless otherwise specified.
2.
All Screening assessments must be performed within 14 days prior to first dose unless otherwise specified. Informed Consent must be signed before any study-specific 
assessments are performed.
3.
Screening examination to include BCVA (best-corrected visual acuity), slit lamp examination (with special focus on cornea), intraocular pressure, and dilated fundoscopic 
examination may be performed within 21 days prior to first dose.
4.
On-study exams to include BCVA (best-corrected visual acuity) and slit lamp examination (with special focus on cornea); window for exams is up to 3 days prior to dosing.  In the 
event that a subject has a dose delay due to a non-ocular toxicity and an ocular exam has been performed for that cycle, a repeat ocular exam 3 days prior to dosing may be 
omitted if the participant did not have corneal signs on the previous exam and does not have any new corneal symptoms. 


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5.
On initial (first infusion) dosing day, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +10 minutes, +30 minutes (±15 min) after SOI, EOI, and 1 hour post 
EOI.  On subsequent dosing days, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +30 minutes after SOI, and EOI.  On days where vital sign 
timepoints align with PK sampling timepoints, vital signs should be assessed prior to PK samples being drawn.  
6.
If completed within 72 hrs prior to the first dose, this assessment need not be repeated on Day 1 of Cycle 1.  Refer to Table 15 of the protocol for a comprehensive list of lab 
tests.  
7.
Troponin will be measured at the local (troponin I or T) and central (troponin I) lab.  
8.
CK-MB at the local lab, or if not available by a central laboratory. 
9.
BNP to be measured locally at screening; if cardiac workup is required due to safety concerns during the study, BNP should be measured.
10. Perform only in women of child-bearing potential.  A serum pregnancy test should be performed at screening, and subsequent pregnancy tests may be either serum or urine.
11. Final pregnancy test (serum or urine) must be performed in women of childbearing potential 60 days after last study treatment.
12. On dosing days, triplicate ECGs to be performed at predose (within 30 minutes prior to SOI) and EOI.  On days where ECG timepoints align with PK sampling timepoints, 
ECGs should be performed prior to PK samples being drawn (PK sample should be taken at the exact nominal time; refer to footnote 18).  At screening, on interim visits 
(C1D8 and C1D15) and End of Study, obtain a single ECG measurement.
13. At Screening, LVEF may be performed within 30 days prior to first dose.  All ECHOs indicated on dosing days may be performed up to 5 days. ECHOs to be done locally and sent 
to GSK for central imaging storage.
14. A single sBCMA sample will be collected at C1D1 predose (within 30 minutes prior to SOI).  On C2D1 sBCMA will be collected at predose (within 30 minutes prior to SOI) and at 
EOI (5 minutes).
15. Collect cytokines at predose (within 30 minutes prior to SOI) and EOI (5 min) (even when infusion is interrupted or halted) to assess allergic reaction.
16. All ADA samples will be collected prior to each infusion.
17. Sample(s) collected for analysis by central lab.
18. PK samples to be taken for both GSK2587916 and cys-mcMMAF measurement on C1D1 at pre-dose (within 30 minutes prior to SOI), at EOI (just before EOI), 1 h after EOI (5 
min), 3 h after EOI (5 min); C2D1, C3D1, and C5D1 at pre-dose (within 30 minutes prior to SOI) and at EOI (just before EOI).
19. Collect 1 PK sample at each subject’s final visit.
20. Informed consent for optional  genetics research should be obtained before collecting a sample.
21. CT/PET or CT scans from within 21 days prior to first dose are acceptable. CT scans are acceptable at all restaging assessments unless CR is suspected, in which case a 
PET/CT scan will be obtained to confirm CR.
22. Study drug administration 3 day window only.
23. Prophylaxis with prednisolone phosphate 1% or dexamethasone 0.1% 1 drops QID x 4 days starting 1 day prior to treatment.
24. Archived or fresh tissue required for BCMA testing.  Refer to Section 5.2.1 of the protocol Inclusion Criterion #4 for eligibility criteria. 
25. Record subject’s survival status until last subject completes or discontinues treatment and whether subsequent treatment for disease was given.  Subject does not need to come 
in for visit.
26. End of treatment visit should be performed within 30 days (+7 days) after the last dose or prior to the start of new anti-cancer treatment, whichever is earlier. In cases where more 
than 30 days (+7 days) have elapsed from the date of the subject’s last dose due to dosing delays and a subsequent decision to take the subject off treatment, the end of study 
treatment visit should be scheduled as soon as possible to allow the final assessments to be performed at the earliest date.
27. All participants should be followed for survival for 1 year from last dose. Participants with corneal signs or symptoms at the end of study treatment visit should be monitored by 
ophthalmic exam every month after the last study dose until deemed clinically stable by an eye care professional or for 12 months (whichever comes first). Corneal exams to 
include BCVA and slit lamp examination (with special focus on cornea).


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Abbreviations:
ADA = Antibody Drug Antibody; ALP = alkaline phosphatase; BCVA = best corrected visual acuity; BNP = B-type natriuretic peptide; C1D1 = Cycle 1 Day 1, etc.; cfDNA = 
Circulating free DNA; CK = creatine kinase; CRP = C-reactive protein; EOI = End of Infusion; PD = Pharmacodynamics; PK = Pharmacokinetics; QID = 4 times a day; SOI = start 
of infusion


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16.2.3.4.
Dose Expansion Weekly Dosing Schedule for Lymphomas
Time and Events Table for Full Study (Cycle = 28 days)
Study Assessments1
Screen2
Day 1 
C1
Day 8 C1
Day 15 
C1
Day 1 
C2
Day 15 
C2
D1 of C3-C16
End of Study 
Treatment
3-Month 
Off-study 
Follow-up
Informed Consent
X
Baseline Demographics
X
Medical History
X
Physical Exam
X
X
X
At the start of each cycle
X
Ocular Exam
X3
X4
At the start of each cycle4
X4
ECOG Performance 
Status
X
X
At the start of each cycle
X
Vital Signs (BP, HR, Body 
Temperature)
X
X5
X5
X5
X5
At the start of each cycle5
X
Weight and Height
X
Weight 
only
Weight 
only
Weight only - At the start of each cycle
Weight
Hematology
X
X6
X
X
X
At the start of each cycle
X
Clinical chemistry
X
X6
X
X
X
X
At the start of each cycle
X
Urine Dipstick
X
X6
X
At the start of each cycle
X
INR, PTT 
X
X6
X
X
X
At the start of each cycle
HBV/HCV tests
X
CK-MB , Troponin 
X7
X7
X7
At the start of each cycle7
X7
BNP
X8
24 hr urine protein and 
albumin 
X
X
At the start of each cycle
IgG, IgM, IgA
X
X
At the start of every other  cycle
CRP, beta2 microglobulin
X
X
At the start of each cycle
Pregnancy Test 
X9
At the start of cycles 59, 99, 139
X9
X10
Chest X-ray
X
12-lead ECG
X11
X11
X11
X11
X11
At the start of each cycle11
X11
LVEF and valves 
assessment (ECHO)
X12
At the start of cycles 412, 912
X12


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Time and Events Table for Full Study (Cycle = 28 days)
Study Assessments1
Screen2
Day 1 
C1
Day 8 C1
Day 15 
C1
Day 1 
C2
Day 15 
C2
D1 of C3-C16
End of Study 
Treatment
3-Month 
Off-study 
Follow-up
Serum (soluble BCMA) 
X13
X13
X13
X13
X13
Serum 
(cytokines/chemokines)
X14
X14
X14
X14
Predose and EOI on D1 of each cycle
X
Serum (anti-drug-
antibodies)
X15
X15
X15
At the start of cycles 315, 615, 915, 1215 and 
1615
X
Plasma-cfDNA 
X
X 
Peripheral blood (flow for 
TBNK)
X16
X16
X16
At the start of each cycle16
X16
Sparse PK (blood) 
X17
X17
X17
X17
X17
C3D117, C3D1517 and C5D117 only
X18
Genetics sample
X19
CT/PET Scan for disease 
assessments 
X20
At the start of Cycles 3, 5, 7, 9, 11, 13, and 
16
Premedication if needed
X
X
X
X24
X
Each dosing week
GSK2857916  
administration
X21
X21
X21
X21, 24
X
Each dosing week21
Steroid eye drops
X22
X22
X22
X22, 24
X22
Each dosing week22
Tumor biopsy for BCMA 
expression
X23
Adverse Events
Continuous
Concomitant Medications
X
Continuous
Survival Status
X25
Subsequent Treatment
X25
1.
Assessments scheduled on days of dosing should be done prior to drug administration, unless otherwise specified.  All other assessments can be done 3 days unless otherwise 
specified
2.
All Screening assessments must be performed within 14 days prior to first dose unless otherwise specified. Informed Consent must be signed before any study-specific 
assessments are performed.
3.
Screening examination to include BCVA (best-corrected visual acuity), slit lamp examination (with special focus on cornea), intraocular pressure, and dilated fundoscopic 
examination may be performed within 21 days prior to first dose.
4.
On-study exams, to include BCVA (best-corrected visual acuity) and slit lamp examination (with special focus on cornea); window for exams is up to 3 days prior to dosing. In the 
event that a subject has a dose delay due to a non-ocular toxicity and an ocular exam has been performed for that cycle, a repeat ocular exam 3 days prior to dosing may be 
omitted if the participant did not have corneal signs on the previous exam and does not have any new corneal symptoms. 


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5.
On initial (first infusion) dosing day, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +10 minutes and +30 minutes after SOI (5 min), EOI, and 1 hour 
post EOI.  On subsequent dosing days, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +30 minutes after SOI, and EOI.  On days where vital sign 
timepoints align with PK sampling timepoints, vital signs should be assessed prior to PK samples being drawn.  
6.
If completed within 72 hrs prior to the first dose, this assessment need not be repeated on Day 1 of Cycle 1.  Refer to Table 15 of the protocol for comprehensive list of lab tests.   
7.
Troponin will be measured at the local (troponin I or T) and central (troponin I) lab.  CK-MB at the local lab, or if not available by a central laboratory. 
8.
BNP to be measured locally, or if not available by a central laboratory, at screening; if cardiac workup is required due to safety concerns during the study, BNP should be 
measured.
9.
Perform only in women of child-bearing potential.  A serum pregnancy test should be performed at screening, and subsequent pregnancy tests may be either serum or urine
10. Final pregnancy test (serum or urine) must be performed in women of childbearing potential 60 days after last study treatment.
11. On dosing days, perform triplicate ECGs at predose (within 30 minutes prior to SOI) and EOI.  On days where ECG timepoints align with PK sampling timepoints, ECGs 
should be performed prior to PK samples being drawn (PK sample should be taken at the exact nominal time; refer to footnote 17).  At screening and End of Study, 
obtain a single ECG measurement.
12. At Screening, LVEF may be performed within 30 days prior to first dose. All ECHOs indicated on dosing days may be performed up to 7 days before dosing. ECHOs to be done 
locally and sent to GSK for central imaging storage.
13. A single sample for sBCMA will be collected at C1D8 predose, and at the End of Study visit.  sBCMA samples will also be collected on C1D1 at predose (within 30 minutes prior to 
SOI) and EOI (5 minutes).  On C1D15 and C2D1 collect at predose (within 30 minutes prior to SOI) and EOI (5 minutes)
14. Collect cytokines at predose (within 30 minutes prior to SOI) and EOI (5 min) (even when infusion is interrupted or halted) to assess allergic reaction.
15. All ADA samples will be collected prior to each infusion.
16. Sample(s) collected for analysis by central lab.
17. PK samples to be taken for both GSK2857916 and cys-mcMMAF measurement at C1D1 predose (within 30 minutes prior to SOI), EOI (just before EOI), 1 hour post EOI (5 min), 
and 3 hours post EOI (5 min); predose (within 30 minutes prior to SOI) and EOI (just before EOI) on C1D8, C1D15, C2D1, C2D15, C3D1, C3D15, and C5D1.
18. Collect 1 PK sample at each subject’s final visit.
19. Informed consent for optional genetics research should be obtained before collecting a sample.
20. CT/PET scans from within 21 days prior to first dose are acceptable.
21. Study drug administration 1 day window only.
22. Prophylaxis with prednisolone phosphate 1% or dexamethasone 0.1% 1 drops QID x 4 days starting 1 day prior to treatment.
23. Archived or fresh tissue required for BCMA testing.  Refer to Section 5.2.1 of the protocol Inclusion Criterion #4 for eligibility criteria. 
24. Also applies to C2D8.
25. Record subject’s survival status and whether subsequent treatment for disease was given.  Subject does not need to come in for visit.
Abbreviations:
ADA = Antibody Drug Antibody; ALP = alkaline phosphatase; BCVA = best corrected visual acuity; BNP = B-type natriuretic peptide; C1D1 = Cycle 1 Day 1, etc.; cfDNA = 
Circulating free DNA; CK = creatine kinase; CRP = C-reactive protein; EOI = End of Infusion; PD = Pharmacodynamics; PK = Pharmacokinetics; QID = 4 times a day; SOI = start 
of infusion


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16.3.
Appendix 3: Assessment Windows
No assessment windows will be applied.


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16.4.
Appendix 4: Study Phases and Treatment Emergent 
Adverse Events
16.4.1.
Study Phases
Study Phase
Definition
Pre-Treatment 
Date ≤ Study Treatment Start Date
On-Treatment
Study Treatment Start Date < Date 
Some datasets include the first dosing day as On-Treatment and some exclude the first 
dosing date as On-Treatment. 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. The first dosing day (Day 1) is considered to be On-Treatment for adverse 
events and concomitant medications.
16.4.1.1.
Study Time Periods for Concomitant Medications and Blood and Blood 
Supportive Care Products
Concomitant Medication and Blood and Blood Supportive Care Product start and end 
dates will be assigned to study time periods in relation to first dose of study treatment as 
defined below. The start date references time flag variables and end date reference time 
flag variables will be added to the concomitant medications and blood and blood 
supportive products datasets, respectively.

Start relative to treatment: Assign to 'BEFORE' if start date is prior to study 
treatment start date or if subject has not taken any study treatment or (start date is 
missing and end date is before study treatment start date). Else assign to 'DURING' if 
the start date falls into the on-therapy period as defined above or if subject is ongoing
(not all study treatment discontinuation records completed) or start date is missing. 
Else assign to 'AFTER' if start date is after the on-therapy period.

End relative to treatment: Assign to 'BEFORE' if end date is prior to study treatment 
start date or if subject has not taken any study treatment. Else assign to 'DURING' if 
start date falls into the on-therapy period or if subject is ongoing (not all study 
treatment discontinuation records completed) or (end date is missing and start 
relative to treatment not 'AFTER'). Else assign to 'AFTER' if start date is after the 
on-therapy period or (end date is missing and start relative to treatment='AFTER').
Only on-therapy blood and blood supportive care products that start after the start of 
study treatment are included in the Blood Products and Blood Supportive Care Product 
summaries. Therefore, for summary tables, include blood and blood supportive care 
product records where start relative to treatment in ('DURING') and end relative to 
treatment in ('DURING','AFTER'). All data will be reported in listings. 
Concomitant medication start relative to treatment and end relative to treatment flags are 
used to select data to include in the Concomitant Medication summaries as follows:

Summary of Concomitant Medications: This summary will contain medications 
including those with start date prior to study treatment start date and continue 


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(missing end date or end date after study treatment start date) on therapy. Note that 
any medications with start date and end date prior to study treatment start date will be 
excluded. In addition, any medication that was started during post-therapy will be 
excluded. Include concomitant medication records where start relative to treatment in 
('BEFORE','DURING') and end relative to treatment in ('DURING','AFTER').

Summary of Concomitant Medications with On-Therapy Onset: This summary will 
contain medications with start date after study treatment start date. In addition, any 
medication that was started during post-therapy (see above for definition of post-
therapy) will be excluded. Include concomitant medication records where start 
relative to treatment in ('DURING') and end relative to treatment in 
('DURING','AFTER').
16.4.2.
Treatment Emergent Flag for Adverse Events
Flag
Definition
Treatment 
Emergent

Study Treatment Start Date ≤ AE Start Date 

AE Start Date is missing
NOTES: 

If the study treatment stop date is missing, then the AE will be considered to be On-Treatment.

Time of study treatment dosing and start/stop time of AEs should be considered, if collected.


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16.5.
Appendix 5: Data Display Standards & Handling 
Conventions
16.5.1.
Reporting Process
Software

The currently supported versions of SAS software will be used.
Reporting Area
HARP Server
: US1SALX00259
HARP Compound
: arprod\gsk2859716\bma117159\
Analysis Datasets 

Analysis datasets will be created according to CDISC standards (SDTM IG Version 3.1.3 & ADaM IG 
Version 1.0.
Generation of RTF Files

RTF files will be generated for all tables.
16.5.2.
Reporting Standards
General

The current GSK Integrated Data Standards Library (IDSL) will be applied for reporting, unless 
otherwise stated (IDSL Standards Location: https://spope.gsk.com/sites/IDSLLibrary/SitePages/Home.aspx):

4.03 to 4.23: General Principles

5.01 to 5.08: Principles Related to Data Listings

6.01 to 6.11: Principles Related to Summary Tables

7.01 to 7.13: Principles Related to Graphics 

Do not include subject level listings in the main body of the GSK Clinical Study Report. All subject level 
listings should be located in the modular appendices as ICH or non-ICH listings
Formats

GSK IDSL Statistical Principles (5.03 & 6.06.3) for decimal places (DP’s) will be adopted for reporting of 
data based on the raw data collected, unless otherwise stated.

Numeric data will be reported at the precision collected on the eCRF.
The reported precision from non eCRF sources will follow the IDSL statistical principles but may be
adjusted to a clinically interpretable number of DP’s.
Planned and Actual Time

Reporting for tables, figures and formal statistical analyses:

Planned time relative to dosing will be used in figures, summaries, statistical analyses and 
calculation of any derived parameters, unless otherwise stated.

The impact of any major deviation from the planned assessment times and/or scheduled visit days
on the analyses and interpretation of the results will be assessed as appropriate.

Reporting for Data Listings: 

Planned and actual time relative to study drug dosing will be shown in listings (Refer to IDSL 
Statistical Principle 5.05.1).

Unscheduled or unplanned readings will be presented within the subject’s listings. 


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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.
16.5.3.
Reporting Standards for Pharmacokinetic Data
Pharmacokinetic Concentration Data
PC Windows Non-
Linear (WNL) File
PC WNL file (CSV format) for the non-compartmental analysis by Clinical 
Pharmacology Modelling and Simulation function will be created according to 
SOP_00000314000 : Non-Compartmental Analysis of Clinical Pharmacokinetic 
Data.
Note: Concentration values will be imputed as per GUI_51487
Descriptive Summary 
Statistics, Graphical 
Displays and Listings
Refer to IDSL PK Display Standards.
Refer to IDSL Statistical Principle 6.06.1.
Note: Concentration values will be imputed as per GUI_51487 for descriptive 
summary statistics/analysis and summarized graphical displays only. 
NONMEM/Pop PK 
File
Pop-PK file (CSV format) for the POP-PK analysis by Clinical Pharmacology 
Modelling and Simulation function will be created according to the data specification 
detailed in Section 16.9.1 Population Pharmacokinetic (PopPK) Dataset
Specification.
NONMEM/PK/PD 
File
PK/PD file (CSV format) for the PK/PD analysis by Clinical Pharmacology Modelling 
and Simulation function will be created according to the data specification detailed 
in Section 16.10.1 Pharmacokinetic/Pharmacodynamic Dataset Specification.
Pharmacokinetic Parameter Derivation
PK Parameter to be 
Derived by 
Programmer
The following PK parameters will be derived by the Programmer: 
Pharmacokinetic Parameter Data
Is NQ impacted PK 
Parameters Rule 
Being Followed
Yes, refer to [Standards for Handling NQ Impacted PK Parameters].
Descriptive Summary 
Statistics, Graphical 
Displays and Listings
Refer to IDSL PK Display Standards. 


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16.5.4.
Extended Loss to Follow-up or Extended Time without an 
Adequate Assessment
For subjects, if two or more scheduled disease assessments are missed and are then 
followed by an assessment of PD or death, PFS will be censored at the last adequate 
assessment prior to PD or death. When the scheduled disease assessment is every 3 
weeks, a window of 49 days (6 weeks + 7 day window) will be used to determine 
whether there was an extended time without adequate assessment. That is, if the time 
difference between PD/death and last adequate assessment is more than 49 days, then 
PFS will be censored at the last adequate assessment prior to PD/death.
16.5.5.
Date Associated with Response
Investigator assessment of disease is entered in the eCRF on the VISIT form. The date of 
the VISIT is captured but the date of the response assessment is not captured separately. 
The date associated with response will be the visit date for the VISIT on which the 
investigator assessed disease. A disease assessment may occur at an unscheduled visit. 
The date of the unscheduled visit would be assigned to any response assessed on that 
date. In the following section, unless otherwise specified, the disease assessment denotes 
post-baseline assessment.


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16.6.
Appendix 6: Derived and Transformed Data
16.6.1.
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    
16.6.2.
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 = Treatment Stop Date – (Treatment Start 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 = Sum of Dose at Each Cycle

Dose intensity per cycle will be based on the formula:
Dose intensity Per Cycle = Cumulative Dose / Total Number of Cycles
16.6.3.
Efficacy
Laboratory Parameters
Serum M-protein, Urine M-protein, Serum FLC

If a laboratory value which is expected to have a numeric value for summary purposes, has a non-
detectable level reported in the database, where the numeric value is missing, but typically a character 
value starting with ‘<x’ or ‘>x’ (or indicated as less than x or greater than x in the comment field) is 
present, the number of significant digits in the observed values will be used to determine how much to 
add or subtract in order to impute the corresponding numeric value. 
o
Example 1: 2 Significant Digits =  ‘< x ‘ becomes x – 0.01
o
Example 2: 1 Significant Digit   =  ‘> x’ becomes x + 0.1
o
Example 3: 0 Significant Digits = ‘< x’ becomes x – 1    


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16.6.4.
Safety
Adverse Events
AE’S OF Interest

Corneal events

Thrombocytopenia

Neutropenia

Hematologic Toxicity

Infusion-related Reactions as collected in the eCRF


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16.7.
Appendix 7: Reporting Standards for Missing Data
16.7.1.
Premature Withdrawals
Element
Reporting Detail
General

Subject study completion (i.e. as specified in the protocol) was defined as:
o
For Part 1 (dose-escalation phase), a completed subject is one who has completed 
at least 1 cycle of study treatment and an End of Study Visit without events 
causing them to withdraw or discontinue from the study for reasons listed in 
Section 6.3 of the protocol.
o
For Part 2 (expansion cohort), a completed subject is one who has received at 
least one dose of study treatment without events causing them to withdraw or 
discontinue study treatment for reasons listed in Section 6.3 of the protocol and 
completed an End of Study Visit.
o
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 before the end of 
the study, has not been lost to follow-up, or has not withdrawn consent from study 
participation.

Withdrawn subjects may be replaced in the study.

All available data from participants who were withdrawn from the study will be listed 
and all available planned data will be included in summary tables and figures, unless 
otherwise specified.
16.7.2.
Handling of Missing Data
Element
Reporting Detail
General

Missing data occurs when any requested data is not provided, leading to blank fields on 
the collection instrument:
o
These data will be indicated by the use of a blank in subject listing displays. Unless 
all data for a specific visit are missing in which case the data is excluded from the 
table. 
o
Answers such as “Not applicable” and “Not evaluable” are not considered to be 
missing data and should be displayed as such.
Outliers

Any participants excluded from the summaries and/or statistical analyses will be 
documented along with the reason for exclusion in the clinical study report.
Responder 
Analysis 

For endpoints which determine the percentage of responders, subjects with 
unknown/not evaluable or missing best overall response will be assumed to be non-
responders, and will be included in the denominator when calculating the percentages.
Time to 
Event 

Because study treatment is dependent on the study endpoints (e.g., progression, i.e. 
not a fixed treatment duration), the length of treatment for each subject will depend on 
the efficacy and toxicity of the treatment, so the duration of treatment will vary across 
subjects. Similarly the duration of follow up will also vary. All available time-to-event 
data will be analyzed using suitable statistical methods; subjects with shorter treatment 
and follow-up due to the natural history of their disease or medical necessities of the 
treatment of their disease will not be considered to have missing time-to-event data.


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16.7.2.1.
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. The imputed AE dates will only to be used 
in the figures “Profile Plot for Patients with No Corneal Event or Grade 1 Corneal Event” and 
“Profile Plot for Patients with Grade 2 or Higher Corneal Events”.

Imputed dates will not be displayed in listings. However, where necessary, display macros may 
impute dates as temporary variables for the purpose of sorting data in listings only. In addition,
partial dates may be imputed for ‘slotting’ data to study time periods or for specific analysis 
purposes as outlined below.
Adverse 
Events

The eCRF allows for the possibility of partial dates (i.e., only month and year) to be recorded for 
AE start and end dates; that is, the day of the month may be missing.
o
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. Missing 
Start Day: First of the month will be used unless this is before the start date of study 
treatment; in this case the study treatment start date will be used and hence the event is 
considered On-treatment as per Appendix 4: Study Phases and Treatment Emergent 
Adverse Events.
o
Missing Stop Day: Last day of the month will be used, 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.
Concomitant 
Medications

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.
Anti-Cancer 
Therapy 
(Where 
applicable),  
Radiotherapy 
and  
Surgical 
Procedures 
for Time-to-
Event 
Endpoint and 
Response

Start dates for follow-up anti-cancer therapy, radiotherapy (where applicable), and surgical 
procedures (where applicable) will be temporarily imputed in order to define event and censoring 
rules for progression-free survival, response rate, time to progression, duration of response or 
time to response (i.e. start date for new anti-cancer therapy). The imputed dates will not be 
stored on the anti-cancer therapy, radiotherapy, or surgical procedure datasets.

If missing start day, month, and year, then no imputation for completely missing dates

If missing start day and month, then no imputation should be done

If missing start day, then do the following:

If partial date falls in the same month as the last dose of study treatment, then assign to earlier 
of (date of last dose of study treatment+1, last day of month). 

If partial date falls in the same month as the subject’s last assessment and the subject’s last 
assessment is PD, then assign to earlier of (date of PD+1, last day of month). 

If both rules above apply, then assign to latest of the 2 dates 

Otherwise, impute missing day to the first of the month.

If missing end date, then no imputation should be done.


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16.8.
Appendix 8: Values of Potential Clinical Importance
16.8.1.
Laboratory Parameters
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 v4.0) will be used to 
assign grades to the relevant laboratory parameters. NCI-CTCAE v4.0 can be found at
http://ctep.cancer.gov/reporting/ctc.html. 
For laboratory data which are not listed in the NCI CTCAE v4.0, a summary of values 
outside the normal range will be provided.
16.8.2.
ECG Parameters and vital signs
For ECG and vital signs, the most updated IDSL standard up to the RAP effective date 
will be followed


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16.9.
Appendix 9: Population Pharmacokinetic (PopPK) Analyses
16.9.1.
Population Pharmacokinetic (PopPK) Dataset Specification
Any deviations between the dataset specification and the final dataset will be documented 
in the population pharmacokinetic analysis report.
General Description:
1.
The type of variables should be either NUM or DATE/TIME unless specified 
otherwise
2.
The dataset is sorted by ID, RTFDD, ANALYTE, ASCENDING EVID unless 
specified otherwise
3.
The data items (columns) in the analysis-ready data file will be in the same order 
as described in the table below.
4.
Exclude observations with DTYPE=IMPUTE
5.
Include PKFL=Y (applicable to all datasets)
6.
Same rules are applied for all baseline covariates. Baseline rules are as follows:
• Use baseline value as defined by Stats in the lab test datasets and fill it on all rows for 
each subject;  
• If not defined by Stats, set to measurement nearest to, but prior to, time of first dose
• Only in cases where Day 1 measurement is not available, but screening measurement is, 
the screening values will be used.
• Only in cases where both the Day 1 measurement as well as screening measurement are 
unavailable, set to -99.
7.
3 significant figures for all values except C, STUDY, SUBJID, ID, CTIME, 
DATE, ANALN, BQL, MDV, MDV2, OCC, CYCLE, CMT, AGE, GENDER, 
CANCER, RACE, ETHN, CNC, EXTSMP
8.
Only subjects with CANCER=0 will be included in this dataset as the data for the 
lymphoma patients will not be fully cleaned at the time of the database cut in 4Q2018.


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Column 
Header
Data Item
Codes
Derivation/Comments
Source data 
set 
C
Line number/exclusion identifier
Row Number
STM
DRM
PFD
Set to line/row number unless one or more of the following conditions are 
met, then set to code: 
•
STM = If a PK sample was taken but the date and/or time of the 
sample is missing and cannot be derived
•
DRM= PK samples for which dosing records are missing
•
PFD=PK samples with CONC reported as NA/NR/NQ/BQL/missing 
at pre-dose in CYCLE =1
derived
STUDYID
Study ID
Unique identifier for a study
adpc
SITEID
Unique identifier for a study site
adsl
USUBJID
Unique subject identifier
adsl
SUBJID
Subject identifier from source data 
SUBJID = SUBJID
adsl
ID
NONMEM subject identifier
Sequential subject identifier across studies after data is sorted by 
SUBJID.  For study BMA117196, the ID will start with 
 For study 
205678, the ID will start with 
derived
AMT
Amount of GSK2857916 given (in 
mg)
AMT = ALTDOSE, where PARAMCD=ALTDOSE only on the dosing line. 
If infusion was stopped early and then restarted, the dosing information 
will be captured with more than one line. Each line will represent a part of 
the infusion (for example from start to first interruption and then from 
restart to end of infusion). AMT will have to be derived separately from 
restart of infusion until it is stopped.
For all other lines use “0” 
adex
INFD
Infusion Duration (day)
INFD is the infusion duration and is computed from start and stop time of 
infusion (in days)
(AENDTM-ASTDTM)/60/60/24
This value will only be used on the dosing line. For all other lines use “0”
If infusion was stopped early and then restarted, INFD will have to be 
derived separately from restart of infusion until it is stopped.
adex
INFH
Infusion Duration (h)
INFH is the infusion duration and is computed from start and stop time of 
infusion (in h)
(AENDTM-ASTDTM)/60/60
This value will only be used on the dosing line. For all other lines use “0”
If infusion was stopped early and then restarted, INFH will have to be 
derived separately from restart of infusion until it is stopped.
adex
PPD
PPD


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Column 
Header
Data Item
Codes
Derivation/Comments
Source data 
set 
RATED
Rate of infusion (mg/day)
RATED = AMT/INFD; This value will only be used on the dosing line. For 
all other lines use “0”
If infusion was stopped early and then restarted, RATED will have to be 
derived separately from restart of infusion until it is stopped.
derived
RATEH
Rate of infusion (mg/h)
RATEH = AMT/INFH
This value will only be used on the dosing line. For all other lines use “0”
If infusion was stopped early and then restarted, RATEH will have to be 
derived separately from restart of infusion until it is stopped.
derived
RTFDD
Relative time from start of first 
infusion on study (day)
RTFDD=((ADTM-ASTDTM)/60/60/24))
adpc, adex
RTFDH
Relative time from start of first 
infusion on study (h)
RTFDH=((ADTM-ASTDTM)/60/60))
adpc, adex
RTLDH
Relative time from start of the most 
recent infusion on study (h) done prior 
to the PK sample
For pre-dose samples, RTLDH will be calculated considering the most 
recent infusion done prior to the sample. For example, the RTLDH for 
the pre-dose in Cycle 2 will be computed from the start time of infusion in 
Cycle 1. 
adpc
RTLDD
Relative time from start of the most 
recent infusion on study (day) done 
prior to the PK sample
RTLDD= RTLDH/24
derived
NOMTLDD
Planned nominal time relative to start 
of most recent infusion (day)
NOMTLDH/24
adpc
NOMTLDH
Planned nominal time relative to start 
of most recent infusion (h)
Derive from PCTPT
when (PCTPT ='PRE-DOSE), NOMTLDH=0;
when (PCTPT='DOSE'), NOMTLDH =0;
when (PCTPT =”30M POST START OF INFUSION (SOI)"), NOMTLDH 
=0.5;
when (PCTPT ="END OF INFUSION (EOI)"), NOMTLDH =1;
when (PCTPT ="1 HOUR POST-EOI"), NOMTLDH =2;
when (PCTPT ="3 HOURS POST-EOI"), NOMTLDH =4;
when (PCTPT ="8 HOURS POST-EOI"), NOMTLDH =9;
when (PCTPT ="24 HOURS POST-EOI"), NOMTLDH =25;
when (PCTPT ="7 DAYS POST-EOI"), NOMTLDH =168;
when (PCTPT ="14 DAYS POST-EOI"), NOMTLDH =336;
when (PCTPT = “PRE-DOSE” and VISIT = CYCLE 2, NOMTLDH = 504;
when (PCTPT ="END OF STUDY"), NOMTLDH =10000;
adpc


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Column 
Header
Data Item
Codes
Derivation/Comments
Source data 
set 
otherwise  NOMTLDH =.;
CLOCK
Clock time sample was obtained
Clock time (24 
h) ‘00:00’
TIMEPART (EVENT and DOSING LINE) 
Format TIME5.
all dataset
DATE
Date of event (MM/DD/YYYY)
DATEPART (EVENT and DOSING LINE)
Format DATE9.
all dataset
ANALYTE
Analyte
1= 
ADC(antibody-
drug conjugate)
2= 
TOTALMAB(tot
al antibody 
including 
complex)
3= MMAF(cys-
mcMMAF)
This value will be used on all lines except for dosing record line where 
missing “0” will be used.
EXCLUDE MAB
PARAMCD in (P1RES, P5RES, P7RES), assign ANALYTE =3, 1, 2 
respectively
Derived from 
adpc
CONC
Plasma concentration (ng/mL) of 
GSK2857916 (antibody-drug 
conjugate), total antibody (including
complex) and cys-mcMMAF
If AVALC=NA/NR/NQ/BQL/missing, set CONC= “0”
Else CONC=AVAL
When PARAMCD=P1RES, then CONC=AVAL/1000
[Convert cys-mcMMAF from pg/mL to ng/mL precision (3 significant 
figures). For example, 0.111 pg/mL= 0.000111 ng/mL]
adpc
DNCONC
Dose-normalized plasma 
concentration [(ng/mL)/(mg/kg)] of 
GSK2857916 (antibody-drug 
conjugate), total antibody (including
complex) and cys-mcMMAF
DNCONC = CONC (ng/mL)/AVAL;
where AVAL=adex.PARAMCD=ADOSE (mg/kg)
For CONC = “0”, set DNCONC = “0”
Derived from 
adpc, adex
CONCNM
Plasma concentration (nM) of 
GSK2857916 (antibody-drug 
conjugate), total antibody (including
complex) and cys-mcMMAF
For ANALYTE = 1, CONCNM = CONC(ng/mL)/152.1
For ANALYTE = 2, CONCNM = CONC(ng/mL)/152.1
For ANALYTE = 3, CONCNM = CONC(ng/mL)/1.045
•
MW of ANALYTE =1 is 152.1 kDa
•
MW of ANALYTE =2 is 152.1 kDa
•
MW of ANALYTE =3 is 1045 Da
For CONC = “0”, set CONCNM = “0”
Derived from 
adpc


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Column 
Header
Data Item
Codes
Derivation/Comments
Source data 
set 
DNCONCNM
Dose-normalized plasma 
concentration [(nM)/(mg/kg)] of 
GSK2857916 (antibody-drug 
conjugate), total antibody (including
complex) and cys-mcMMAF
DNCONCNM = CONCNM (nM)/ AVAL;
where AVAL=adex.PARAMCD=ADOSE (mg/kg)
For CONCNM = “0”, set DNCONCNM = “0”
Derived from 
adpc
LNCONC
Natural logarithm of the plasma 
concentration of GSK2857916 
(ng/mL) (antibody-drug conjugate), 
total antibody (including
complex) and cys-mcMMAF
• If CONC = “0” then LNCONC = “0”
• Else LNCONC = loge(CONC)
Derived from 
adpc
LNDNCONC
Natural logarithm of dose-normalized 
plasma concentration 
[(ng/mL)/(mg/kg)] of GSK2857916 
(antibody-drug conjugate), total 
antibody (including
complex) and cys-mcMMAF
If DNCONC = “0” then LNDNCONC = “0”
Else LNDNCONC = loge(DNCONC)
Derived from 
adpc
LNCONCNM
Natural logarithm of plasma 
concentration (nM) of GSK2857916 
(antibody-drug conjugate), total 
antibody (including
complex) and cys-mcMMAF
If CONCNM = “0” then LNCONCNM = “0”
Else LNCONCNM = loge(CONCNM)
Derived from 
adpc
LNDNCONCN
M
Natural logarithm of dose-normalized 
plasma concentration [(nM)/(mg/kg)] 
of GSK2857916 (antibody-drug 
conjugate), total antibody (including
complex) and cys-mcMMAF
If DNCONCNM = “0” then LNDNCONCNM = “0”
Else LNDNCONCNM = loge(DNCONCNM)
Derived from 
adpc
CONC2
Plasma concentration (ng/mL) of 
GSK2857916 (antibody-drug 
conjugate), total antibody (including
complex) and cys-mcMMAF with 
imputation for BQL data
If adpc.AVALC=NA/NR/missing, set CONC2= “0” 
If AVALC=NQ/BQL, set CONC2 = “LLOQ/2”
When PARAMCD=P1RES, then CONC2=AVAL/1000;
[Convert cys-mcMMAF from pg/mL to ng/mL precision (3 significant 
figures). For example, 0.111 pg/mL= 0.000111 ng/mL]
LLOQ for ANALYTE=1 is 100 ng/mL (adpc.PCLLOQ for 
PARAMCD=P5RES)
LLOQ for ANALYTE=2 is 200 ng/mL (adpc.PCLLOQ for 
Derived from 
adpc


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Column 
Header
Data Item
Codes
Derivation/Comments
Source data 
set 
PARAMCD=P7RES)
LLOQ for ANALYTE=3 is 0.05 ng/mL (adpc.PCLLOQ for 
PARAMCD=P1RES; as it is in pg/mL, needs to be converted to ng/mL);
DNCONC2
Dose-normalized plasma 
concentration[(ng/mL)/(mg/kg)] of 
GSK2857916 (antibody-drug 
conjugate), total antibody (including
complex) and cys-mcMMAF with 
imputation for BQL data
DNCONC2 = CONC2(ng/mL)/ AVAL;
where AVAL=adex.PARAMCD=ADOSE (mg/kg)
For CONC2 = “0”, set DNCONC2 = “0”
Derived from 
adpc, adex
CONCNM2
Plasma concentration (nM) of 
GSK2857916 (antibody-drug 
conjugate), total antibody (including
complex) and cys-mcMMAF with 
imputation for BQL data
For ANALYTE = 1, CONCNM2 = CONC2(ng/mL)/152.1
For ANALYTE = 2, CONCNM2 = CONC2(ng/mL)/152.1
For ANALYTE = 3, CONCNM2 = CONC2(ng/mL)/1.045
For CONC2 = “0”, set CONCNM2 = “0”
Derived from 
adpc
DNCONCNM2 Dose-normalized plasma 
concentration [(nM)/(mg/kg)] of 
GSK2857916 (antibody-drug 
conjugate), total antibody (including
complex) and cys-mcMMAF with 
imputation for BQL data
DNCONCNM2 = CONCNM2 (nM)/ADOSE (mg/kg)
For CONCNM2 = “0”, set DNCONCNM2 = “0”
Derived from 
adpc
LNCONC2
Natural logarithm of the plasma 
concentration of GSK2857916 
(ng/mL) (antibody-drug conjugate), 
total antibody (including
complex) and cys-mcMMAF with 
imputation for BQL data
• If CONC2 = “0” then LNCONC2 = “0”
• Else LNCONC2 = loge(CONC2)
Derived from 
adpc
LNDNCONC2
Natural logarithm of dose-normalized 
plasma concentration 
[(ng/mL)/(mg/kg)] of GSK2857916 
(antibody-drug conjugate), total 
antibody (including
complex) and cys-mcMMAF with 
imputation for BQL data
If DNCONC2 = “0” then LNDNCONC2 = “0”
Else LNDNCONC2 = loge(DNCONC2)
Derived from 
adpc
LNCONCNM2 Natural logarithm of plasma 
If CONCNM2 = “0” then LNCONCNM2 = “0”
Derived from 


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Column 
Header
Data Item
Codes
Derivation/Comments
Source data 
set 
concentration (nM) of GSK2857916 
(antibody-drug conjugate), total 
antibody (including
complex) and cys-mcMMAF with 
imputation for BQL data
Else LNCONCNM2 = loge(CONCNM2)
adpc
LNDNCONCN
M2
Natural logarithm of dose-normalized 
plasma concentration [(nM)/(mg/kg)] 
of GSK2857916 (antibody-drug 
conjugate), total antibody (including
complex) and cys-mcMMAF with 
imputation for BQL data
If DNCONCNM2 = “0” then LNDNCONCNM2 = “0”
Else LNDNCONCNM2 = loge(DNCONCNM2)
Derived from 
adpc
BQL
Flag for BQL concentration
0 or 1
Set to 1 if adpc.AVALC= NQ/BQL; 
Else set to 0
adpc
MDV
Missing dependent variable flag.
0 or 1
1 for CONC = “0” and dosing line. 
0 otherwise
adpc
MDV2
Missing dependent variable flag 2
0 or 1
1 for CONC2= “0” and dosing line. 
0 otherwise
adpc
EVID
Flag indicating whether it is dosing 
admin info or drug concentration data.
0 or 1
1 on dosing line
Set to 0 for all other lines
adex, adpc
CYCLE
Cycle number
>0
1 = Cycle 1, 2 = Cycle 2, 3 = Cycle 3, 4 = Cycle 4, 5 = Cycle 5,… etc
EOT=999
Derive from AVISIT
Fill CYCLE on all rows
Note: Pre-dose belongs to the same cycle as the post dose sample done 
on the same day.
adpc
OCC
Occasion
If adpc.PCTPT=PRE-DOSE and CYCLE >= 2, then OCC= CYCLE-1, 
else OCC=CYCLE
Fill OCC on all rows
Note: This is different from CYCLE variable. OCC considers pre-dose 
sample to be part of prior cycle.
derived
EXTSMP
Subjects with extensive 
sampling/data
0= Subjects 
which do 
not have 
1 will be assigned to subjects which have at least 4 CONC values above 
BLQ for either ANALYTE=1 or ANALYTE=3 up in OCC=1 
0 for remaining subjects 
adpc


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Column 
Header
Data Item
Codes
Derivation/Comments
Source data 
set 
extensive 
CONC for 
ADC/MM
AF
1= Subjects 
with extensive 
CONC for 
ADC/MMAF
Fill EXTSMP on all rows
IDOSE
GSK2857916 initial cycle dose 
(mg/kg)
>0
IDOSE=adex.TRT01A; strip off units
adex
ADOSE
GSK2857916 actual cycle dose 
(mg/kg)
>0
ADOSE= AVAL;
where AVAL=adex. PARAMCD=ADOSE
adex
CMT
Compartment
>0
1 = Dosing line 
1= Central Compartment for antibody-drug conjugate when ANALYTE=1
3 = Central Compartment for total antibody (including complex) when 
ANALYTE=2
5 = Central Compartment for cys-mcMMAF when ANALYTE=3
RACET
Subject race text
Use CRF/Stats 
coding
RACET=adrace.ARACE
Fill in RACET in all rows for each subject
adrace
RACEN
Subject race numeric
4 - ASIAN - JAPANESE HERITAGE
3 - ASIAN - SOUTH EAST ASIAN HERITAGE
2 - BLACK OR AFRICAN AMERICAN
1 - WHITE - ARABIC/NORTH AFRICAN HERITAGE
0 - WHITE - WHITE/CAUCASIAN/EUROPEAN HERITAGE
adrace
ETHN
Subject ethnicity
Same coding 
as CRF/Stats
Fill in ETHN in all rows for each subject
-
If missing, ETHN = -99
adsl
AGE
Age (years)
•
Use value as defined by Stats; 
•
If not defined by Stats, AGE = date of first dose – date of birth
•
If date of birth is missing, AGE = -99
adsl
SEX
Gender
0 or 1
Male = 1
Female = 0
adsl


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Column 
Header
Data Item
Codes
Derivation/Comments
Source data 
set 
•
If sex is missing, SEX = -99
BWT
Baseline Weight (kg)
Use Baseline covariate rules.
Fill in BWT in all rows for each subject
adsl
WT
Weight (kg)
WT is propagated forward from the most recent measurement for all 
observations up to the next WT measurement (LOCF). Please capture 
the values corresponding to the PK time points.
advs
HT
Height (cm)
Height at baseline in cm
Fill in HT in all rows for each subject
adsl
BBSA
Baseline Body Surface Area (m2)
Baseline BSA (m2)
BSA = 0.024265 • HT(cm)0.3964 • BWT(kg)0.5378
Ref: Geometric method for measuring body surface area: a height-weight 
formula validated in infants, children, and adults. Haycock GB, Schwartz 
GJ, Wisotsky DH.
Use baseline covariate rules
derived
BSA
Body Surface Area (m2)
BSA (m2)
BSA = 0.024265 • HT(cm)0.3964 • WT(kg)0.5378
BSA is propagated forward from the most recent measurement for all 
observations up to the next BSA measurement (LOCF). Please capture 
the values corresponding to the PK time points.
derived
BBMI
Baseline Body Mass Index (kg/m2)
BBMI = BWT(kg)/(HT(cm)/100)2
Assign BBMI = -99 if negative values would be derived for any of BBMI
Use baseline covariate rules
derived
BMI
Body Mass Index (kg/m2)
BMI = WT(kg)/(HT(cm)/100)2
Assign BMI = -99 if negative values would be derived for any of BMI
BMI is propagated forward from the most recent measurement for all 
observations up to the next BMI measurement (LOCF). Please capture 
the values corresponding to the PK time points.
derived
CANCER
Cancer type
0 or 1
0=Multiple Myeloma, 1=BCMA positive Lymphomas
If TRT01AN = 12, then CANCER=1, else CANCER=0 Fill in CANCER in 
all rows for each subject
all datasets
BSBCMA
sBCMA level at baseline (ng/mL)
Baseline value is pre-dose on Cycle 1 Day 1. For PARAMCD = 
SBCMAG, get the values from AVAL column.
When AVAL is missing:
•
and AVALC = ALQ:  set to LBULOQ
•
and AVALC = BLQ:  set to LBLLOQ/2 
adbiomrk
PARAMCD = 
SBCMAG 
when 
ABLFL=Y.


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Column 
Header
Data Item
Codes
Derivation/Comments
Source data 
set 
•
and AVALC = missing:  set to -99
Use baseline covariate rules
SBCMA
sBCMA level (ng/mL)
For PARAMCD = SBCMAG, get the values from AVAL column.
SBCMA is propagated forward from the most recent measurement for all 
observations up to the next sBCMA measurement (LOCF).
When AVAL is missing:
•
and AVALC = ALQ:  set to LBULOQ
•
and AVALC = BLQ:  set to LBLLOQ/2 
•
and AVALC = missing:  propagate prior SBCMA value forward 
until the next measured SBCMA
Please capture the values corresponding to the PK time points.
adbiomrk
PARAMCD = 
SBCMA
SBCMAGC
Complex BCMA (ng/mL)
For PARAMCD = SBCMAGC, get the values from AVAL column.
SBCMAGC is propagated forward from the most recent measurement for 
all observations up to the SBCMAGC measurement (LOCF).
When AVAL is missing:
•
and AVALC = ALQ:  set to LBULOQ
•
and AVALC = BLQ:  set to LBLLOQ/2 
•
and AVALC = missing:  propagate prior SBCMAGC value 
forward until the next measured SBCMAGC
Please capture the values corresponding to the PK time points.
adbiomrk
PARAMCD = 
SBCMAGC
BCRCL
Baseline Creatinine Clearance 
(mL/min/1.73 m2)
eGFR = 175 × (Scr)-1.154 × (Age)-0.203 × (0.742 if female) × (1.212 if African 
American)
Scr = AVAL; AVAL=adlab.PARAMCD =LB1404 and ABLFL=Y
Convert units (µmol/L) to (mg/dL) using the following formula:
To convert µmol/L to mg/dL, multiply by 0.0113.
Age is expressed in years.
Use baseline covariate rules
Ref: Protocol
adlb;
PARAMCD=L
B1404


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Column 
Header
Data Item
Codes
Derivation/Comments
Source data 
set 
CRCL
Creatinine Clearance (mL/min/1.73 
m2)
To be computed with same equation as provided for BCRCL
CRCL is propagated forward from the most recent measurement for all 
observations up to the next CRCL measurement (LOCF). Please capture 
the values corresponding to the PK time points.
adlb
BALT
Baseline ALT (IU/L)
BALT = AVAL; AVAL=adlab. PARAMCD =LB1227 and ABLFL=Y
Use baseline covariate rules
adlb
ALT
ALT (IU/L)
ALT = AVAL; AVAL=adlab. PARAMCD =LB1227 and ABLFL=Y
ALT is propagated forward from the most recent measurement for all 
observations up to the next ALT measurement (LOCF). Please capture 
the values corresponding to the PK time points.
adlb
BAST
Baseline AST (IU/L)
BAST = AVAL; AVAL=adlab. PARAMCD =LB1273 and ABLFL=Y
Use baseline covariate rules
adlb
AST
AST (IU/L)
AST = AVAL; AVAL=adlab. PARAMCD =LB1273 and ABLFL=Y
AST is propagated forward from the most recent measurement for all 
observations up to the next AST measurement (LOCF). Please capture 
the values corresponding to the PK time points.
adlb
BALB
Baseline Albumin (g/L)
BALB = AVAL; AVAL=adlab. PARAMCD =LB1216 and ABLFL=Y
Use baseline covariate rules
adlb
ALB
Albumin (g/L)
ALB = AVAL; AVAL=adlab. PARAMCD =LB1216 and ABLFL=Y
ALB is propagated forward from the most recent measurement for all 
observations up to the next ALB measurement (LOCF). Please capture 
the values corresponding to the PK time points.
adlb
BTBIL
Baseline Total Bilirubin (mg/dL)
TBIL = AVAL; AVAL=adlab. PARAMCD =LB1282 and ABLFL=Y
adlb


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Column 
Header
Data Item
Codes
Derivation/Comments
Source data 
set 
Use baseline covariate rules
TBIL
Total Bilirubin (mg/dL)
TBIL = AVAL; AVAL=adlab. PARAMCD =LB1282 and ABLFL=Y
TBIL is propagated forward from the most recent measurement for all 
observations up to the next TBIL measurement (LOCF). Please capture 
the values corresponding to the PK time points.
adlb
BCRP
Baseline C Reactive Protein (mg/L)
Use baseline covariate rules
adlb
CRP
C Reactive Protein (mg/L)
CRP is propagated forward from the most recent measurement for all 
observations up to the next CRP measurement (LOCF). Please capture 
the values corresponding to the PK time points.
BIGG
Baseline serum IgG (g/L)
BIGG = AVAL; AVAL=adlab. PARAMCD =LB1566 and ABLFL=Y
Use baseline covariate rules
adlb
IGG
Serum IgG (g/L)
IGG = AVAL; AVAL=adlab PARAMCD =LB1566
Missing values use -99.
IGG is propagated forward from the most recent measurement for all 
observations up to the next IGG measurement (LOCF). Please capture 
the values corresponding to the PK time points.
adlb
MAXPRED
Maximum reduction in M-protein or 
FLC
Obtain AVAL for PARAMCD=MAXPRED.
When AVAL is missing, MAXPRED = -999 
adrs
RESPRATIO
Transform MAXRED to a ratio to 
baseline
RESPRATIO = max((100+MAXPRED)/100,0.001)

When MAXRED is missing, MAXPRED = -999 and 
RESPRATIO= -99

When MAXPRED is less than -100 e.g. -100.15, RESPRATIO = 
negative (It is negative but greater than -8.99), then update 
RESPRATIO = 0.001 

When MAXPRED is equal to -100, RESPRATIO = 0, then 
update RESPRATIO = 0.001
adrs
COUNTRY 
Country code 
Fill in COUNTRY in all rows for each subject
adsl
CNC 
NONMEM Country code 
1 = Canada, 
2 = UK 
Fill in CNC in all rows for each subject
adsl


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Column 
Header
Data Item
Codes
Derivation/Comments
Source data 
set 
3 = US
IMMU
Immunogenicity Outcome 
by Collection Time
0 = 
negative
1 = positive
PARAMCD
IMMU
PARAMCD = 
AGBABDS
PARAMCD = AGBABDC
AVAL
C
NEGATIVE
MISSING
0
AVAL
C
POSITIVE
POSITIVE
1
AVAL
C
POSITIVE
NEGATIVE
0
AVAL
C
POSITIVE
MISSING
-99
AVAL
C
MISSING
ANY
-99
IMMU may not have been assayed at all PK visits. For 
visits between IMMU visits, imputation rules are as 
follows:
(1) When there is no change in IMMU between IMMU 
visits, all PK visits in between will be imputed with 
adis


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Column 
Header
Data Item
Codes
Derivation/Comments
Source data 
set 
the same IMMU
(2) When IMMU changes from 0 to 1, impute 
IMMU=1 from the first record after the record 
known to be IMMU=0
(3) When IMMU changes from 1 to 0, impute IMMU 
= 1 until the record known to be IMMU=0
Only AVISIT and Day of collection is mentioned for 
these samples. Exact clock time information is missing. 
The workaround is to assign PREDOSE CYCLE 1 
CTIME to SCREENING immunogenicity samples. For 
other cycles, as samples were collected at pre-dose, 
PREDOSE PK time is assigned. For EOT 
immunogenicity samples, CTIME will be same as PK 
time point. Use LOCF principle and do not include 
samples which were collected at non-PK time points 
except when it is positive. In this dataset, there were no 
confirmatory positive outcome, so LOCF principle will 
suffice. 
IMM
Overall Immunogenicity Outcome
0=anti-GSK2857916 negative, 1=anti-
0 = 
negative

If IMMU = 1 at any observation for a subject, IMM = 1

else if all IMMU = -99, IMM = -99
adis


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Column 
Header
Data Item
Codes
Derivation/Comments
Source data 
set 
GSK2857916 positive (at least one 
postdose) 
1 = positive
-99 = missing
Else IMM = 0
Fill in IMM in all rows for each subject
ORDRESP
Best Confirmed Response
0,1,2,3,4,5,
6
For PARAMCD=BCRSP, assign 
0 for PD
1 for SD
2 for MR
3 for PR
4 for VGPR
5 for CR
6 for sCR
Fill on all rows
adrs
BECOG 
Baseline ECOG status
0
1
2
Fill on all rows
adqs
ECOG 
ECOG status
0
1
2
Fill on all rows
PRIORRX
Prior line of therapy
When addc.PARAMCD= LTXCPSCR, then PRIORRX = AVALC (Extract
only the number and not the text)
For AVALC = MORE THAN 10 LINES, PRIORRX=11
Fill on all rows
addc


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Column 
Header
Data Item
Codes
Derivation/Comments
Source data 
set 
REFRAC
Refractory status
0 = Double
1 = Other
Fill on all rows
MMTY
Type of Multiple Myeloma
0 = 
Secretory
1= Non-
secretory
When addc.MMYELOTY=SECRETORY, MMTY=0
When addc.MMYELOTY= NONSECRETORY, MMTY=1
If addc.MMYELOTY is missing, assign MMTY=-99
Fill on all rows.
addc
MMIGTY
Myeloma immunoglobulin
0 = IGA
1 = IGG
2 = IGM
3 = 
OTHER
When addc.PARAMCD=MYELOIG and AVALC=IGA, then MMIGTY =0
When addc.PARAMCD=MYELOIG and AVALC=IGG, then MMIGTY =1
When addc.PARAMCD=MYELOIG and AVALC=IGM, then MMIGTY =2
For AVALC which is not equal to IGA/ IGG /IGM, then MMIGTY=3
Fill on all rows
addc
BSTAGE
Stage at Screening
0 = I
1 = II
2 = III
3 = 
UNKNOW
N or 
When addc.PARAMCD = STAGESCR and AVALC = I, then BSTAGE = 0
When addc.PARAMCD = STAGESCR and AVALC = II, then BSTAGE = 
1
When addc.PARAMCD = STAGESCR and AVALC = III, then BSTAGE = 
2
When addc.PARAMCD = STAGESCR and AVALC = UNKNOWN or 
missing , then BSTAGE = 3
Fill on all rows
addc


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Column 
Header
Data Item
Codes
Derivation/Comments
Source data 
set 
missing
MMLCTY
Myeloma Light Chain
0 = 
KAPPA 
LIGHT 
CHAIN
1 = 
LAMBDA 
LIGHT 
CHAIN
When addc.PARAMCD = MYELOLC and AVALC = KAPPA LIGHT 
CHAIN, then MMLCTY = 0
When addc.PARAMCD = MYELOLC and AVALC = LAMBDA LIGHT 
CHAIN, then MMLCTY = 1
Fill on all rows
addc


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16.9.2.
Population Pharmacokinetic (PopPK) Methodology
The primary goal of this analysis is to characterize the population pharmacokinetics of 
GSK2857916 and associated analytes after intravenous administration of GSK2857916 in 
subjects with multiple myeloma. This analysis will be performed by CPMS and reported 
separately. 
A summary of the planned population pharmacokinetic analyses is outlined below:

Exploratory data analyses will be performed to understand the content of the analysis 
dataset with respect to the anticipated models, to search for extreme values and/or 
potential outliers, to examine the correlation between covariates, and to assess 
possible trends in the data. 

Drug concentration-time data will be subjected to nonlinear mixed effects modelling 
using appropriate validated software to develop a population PK model.

Based on the preliminary analysis, log-transformed drug concentration data for 
GSK2857916 ADC will be subjected to analysis using a two-compartment IV 
infusion model parameterized using either clearances and distribution volumes, 
micro-constants or macro-constants (A, B, ALPHA and BETA), depending on 
parameters to be estimated. A similar approach may be used on the data from the 
three analytes (ADC, total antibody, and cys-mcMMAF) together.

Inter-individual or between-subject variability (IIV or BSV) will be initially modeled 
using an exponential random effects model. Random effects for clearances and 
volumes or A and B and BETA will be incorporated, depending on model
parameterization used. If the goodness-of-fit plots reveal potential biases in the 
random effects model, alternative random effects models may be considered.

An additive error model on a log-transformed data scale reflecting an exponential 
error residual variability model will initially be used to describe the residual 
variability. If the goodness-of-fit plots reveal potential biases in the residual 
variability model, other residual error models will be considered as appropriate. 

Covariate analysis will be performed to explore measurable sources of PK 
variability. Different approaches may be evaluated for covariate model building 
including a step-wise process consisting of a forward and a backward selection 
procedure and/or a full-model approach. Some of the prospectively identified 
covariates are listed below: 

Continuous covariates such as age, albumin, measures of body size (e.g., body 
weight, body surface area, body mass index, lean body mass); 

Categorical covariates such as gender, race, disease status, immunogenicity 
status, and geographic region.

Non-parametric bootstrapping may be performed to test model robustness. The 
model performance may be evaluated by performing predictive check. 

Individual post hoc estimated PK parameters will be summarized descriptively.  


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116

Individual subject PK parameters and exposure measures for Cycle 1 will be 
estimated and documented for the purposes of any subsequent exposure-response 
(PK/PD) analyses.
Any analyses not described a priori but undertaken based on emerging data will be 
described in detail in the report.
Data handling considerations are summarized below:

Drug concentration data which are below the lower limit of quantification, LLQ, 
(NQ or BLQ) are not reported as a numeric value. Such NQ observations will be 
either discarded or handled in a special way. When the frequency of NQ is small, the 
NQ values will be excluded, since discarding NQ values in this case introduces little 
bias [Beal, 2001]. In situations where there are a large percentage of NQ values, 
other strategies which may reduce estimation bias will be considered [Beal, 2001; 
Hing, 2001; Ahn, 2008]. The total number and percentage of NQ values will be 
calculated and the rationale for the method for handling these NQ values will be 
documented in the final report. In situations with large number of NQ values, the 
predictive performance of the model will be assessed to compare the agreement 
between observed versus predicted proportion of samples below the LLQ.

Concentrations that are inconsistent pharmacokinetically with the drug 
concentration-time profile within an individual may be considered as outliers and 
subsequently excluded from the dataset or analysis. Visual inspection of individual 
and pooled data and weighted residuals during analysis may be used to identify such 
outliers. Any such exclusion will be reported and discussed in the analyses summary.

Missing data will be handled in the following way:

Subjects who withdrew from the study and did not provide any PK samples and 
do not have adequate sampling and/or covariate information will be excluded 
from the analysis.

If dosing and/or sampling times are missing, the relevant concentrations may be 
excluded from the analysis dataset and summarized in an exclusion listing file. 
Alternatively, the nominal times of the respective doses and/or samples may be 
utilized. 

Imputations of any covariate value will only be performed if the variable is 
missing for less than 10% of the subjects. For continuous covariates, missing 
values for an individual subject will be imputed as the gender-specific median 
value for the study. Any changes to the imputation methods will be justified and 
documented. If the percentage of missing data is greater than 10%, the variable 
will only be evaluated in exploratory graphical displays and not in the 
population analyses. Subjects from race categories with an insufficient number 
for analysis (typically less than 10% of the subject population) may be re-
grouped and/or defined as race “Other.”


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16.10.
Appendix 10: Pharmacokinetic / Pharmacodynamic 
Analyses
16.10.1.
Pharmacokinetic / Pharmacodynamic Dataset Specification
Dataset specifications for exposure-response analyses of efficacy and of corneal toxicity 
are provided.  Any deviations between the dataset specifications and the final datasets 
will be documented in the population pharmacokinetic analysis report.
For corneal events: 
General Description:
1.
The dataset is sorted by SUBJID
2.
Three significant figures for all values except those variables which are integers.
3.
Only subjects with CANCER=0 will be included in this dataset as the data for the 
lymphoma patients will not be fully cleaned at the time of the database cut in 4Q2018. 
Column Header
Data Item
Codes
Derivation/Comments
Source 
data set
C
Line 
number/exclusion 
identifier
Row 
Number
Set to line/row number 
adae
STUDY
Study ID
1 = BMA117159
adsl
USUBJID
Unique subject 
identifier
adsl
SUBJID
Subject identifier 
from source data 
SUBJID = SUBJID
adsl
ID
NONMEM 
subject identifier
Sequential subject identifier across studies 
after data is sorted by SUBJID. Starting with 
TOXTYPE
This variable is 
created to 
separate out 
Grade 1 toxicity 
from Grade 2 and 
higher.
1,2
2 separate datasets with one line per subject:
TOXTYPE = 1 for 1st occurrence of corneal 
event (CQ01NAM = Corneal Event). If 
CQ01NAM = missing, add 1 line for that 
subject.
adae
CORTOX
Presence or 
Absence of 
Corneal toxicity
0 or 1
When CQ01NAM ="Corneal Event", then 
CORTOX=1.
When CQ01NAM =missing, then CORTOX=0.
adae
AETOXGRN
Standard Corneal 
Toxicity Grade
0,1,2,3
adae
WRAETOXGRN
Worst Corneal 
Toxicity Grade
0,1,2,3
Worst corneal toxicity grade experienced by 
subject throughout the entire treatment 
duration
adae
TTECORTOX
Time to corneal 
toxicity event 
(day)

For TOXTYPE = 1 and CORTOX = 
1, then TTECORTOX = AESTDY 

When TOXTYPE = 1 and CORTOX 
= 0, then TTECORTOX = LSTCTDT 
– TRTSDT+ 1 (TRTSDT, LSTCTDT 
is coming from adsl dataset)
adae,
adsl
P


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118
Column Header
Data Item
Codes
Derivation/Comments
Source 
data set

DOAE
Duration of 
adverse event 
(days)
This variable is for calculating the duration of 
adverse event following the 1st occurrence of 
corneal event in TOXTYPE =1 

When CQ01NAM = Corneal Event 
and AONGO=N and AENDTF= 
blank, then DOAE = ADURN; 

When CQ01NAM = Corneal Event 
and AONGO = N and AENDTF= 
Y/M/D, then DOAE = -99; 

When CQ01NAM = Corneal Event 
and AONGO=Y, then DOAE =
(LSTCTDT – ASTDT) + 1; 

When CQ01NAM = Corneal Event 
and AONGO=Y, DOAE = -99 
ASTDTF is not missing (has 
alphabet Y/M/D);

When CQ01NAM = Corneal Event 
and AONGO=Y, DOAE = -99 if  
LSTCTDT or ASTDT is missing;

When CQ01NAM = missing, then 
DOAE = 0; 
adae, 
adsl
DOAECFLCD
DOAE 
Censoring Flag 
Code
0 or 1
When AONGO=N, then DOAECFLCD=0
When AONGO=Y, then DOAECFLCD=1
adae
LNDOAE
Log of duration of 
adverse event
LNDOAE = Log(DOAE);
When DOAE=-99, LNDOAE =-99;
When DOAE=0, LNDOAE=0
adae
CUMAMTCT
Cumulative dose 
to TTECORTOX 
(mg)
When CORTOX=1,

For adex.PARAMCD=ALTDOSE, 
CUMAMTCT= Cumulative of 
adex.AVAL  till adae.AESTDY

For corneal toxicity that occurred on 
dosing days, the dose on the 
corneal toxicity day was not 
included in the cumulative dose 
calculation. Here is the code for 
that:
When adae.AESTDY=adex.ASTDY, 
then CUMAMTCT= Cumulative of 
adex.AVAL  till (adae.AESTDY -1)
When CORTOX=0, 

CUMAMTCT= AVAL* WEIGHTBL;
Get AVAL for 
adex.PARAMCD=CUMDOSE
adex. 
adae
TAAUCCT
Time-average 
AUC till 
The area under the plasma ADC 
concentration–time curve (AUC) per day 
popPK 
output, 


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Column Header
Data Item
Codes
Derivation/Comments
Source 
data set
TTECORTOX 
(AUC/day)
(AUC/day) will be derived for each patient 
using the available ADC dosing information, 
individual patient clearance values from the 
population pharmacokinetic model, and the 
time to the occurrence of the corneal toxicity.
adae
CANCER
Cancer type
0 or 1
0=Multiple Myeloma, 1=BCMA positive 
Lymphomas
If TRT01AN = 12, then CANCER=1, else 
CANCER=0
adsl
AMT
Amount (in mg) 
of GSK2857916 
given in first 
cycle 
AMT = AVAL when PARAMCD=ALTDOSE 
and AVISIT= CYCLE 1 DAY 1
adex
IDOSE
GSK2857916 
initial cycle dose 
(mg/kg)
>0
IDOSE=adex.TRT01A; strip off units
adex
CMAX
First dose Cmax 
of ADC – model 
predicted  EOI 
concentration in 
Cycle 1 (ng/mL)
Individual model predicted conc. at EOI.
PopPK 
output
MMAFCMAX
First dose Cmax. 
of MMAF –
model predicted 
24 HOURS 
POST-EOI in 
Cycle 1 (ng/mL)
Individual model predicted conc. at 24 
HOURS POST-EOI in Cycle 1
PopPK 
output
CTAU
First dose Ctau of 
ADC– model 
predicted pre-
dose 
concentration 
Cycle 2
Individual model predicted pre-dose 
conc.CYCLE 2.
PopPK 
output
AUC
First dose 
AUC(0-inf) of 
ADC (ug.day/mL)
First dose (mg)/Individual Clearance of ADC 
(L/Day)
popPK 
output
MMAFAUC
First dose 
AUC(0-inf) of 
MMAF 
(ug.day/mL)
First dose (mg)/Individual Clearance of MMAF 
(L/Day)
popPK 
output
TOTCYC
Total number of 
CYCLES
TOTCYC=AVAL,
AVAL for adex.PARAM=Total Number of 
Cycles
adex
ETHN
Subject ethnicity
Same 
coding as 
CRF/Stats
Fill in ETHN in all rows for each subject
If missing, ETHN = -99
adsl
AGE
Age (years)
Use value as defined by Stats;
SEX
GENDER
0 or 1
Male = 1
Female = 0
•
If sex is missing, GENDER = -99
BWT
Baseline Weight 
(kg)
•
Use baseline value as defined by 
Stats in the lab test datasets;  
•
If not defined by Stats, set to weight 
measurement nearest to, but prior to, time of 
first dose


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Column Header
Data Item
Codes
Derivation/Comments
Source 
data set
•
Only in cases where Day 1 weight is 
not available, but screening weight is, the 
screening values will be used.
BECOG 
Baseline ECOG 
status
0
1
2
Fill on all rows
ECOG 
ECOG status
0
1
2
ECOG is propagated forward from the most 
recent measurement for all observations up to 
the next ECOG measurement (LOCF). Please
capture the values corresponding to the PK 
time points.
PRIORRX
Prior line of 
therapy
When addc.PARAMCD= LTXCPSCR, then 
PRIORRX = AVALC (Extract only the number 
and not the text)
For AVALC = MORE THAN 10 LINES, 
PRIORRX=11
Fill on all rows
addc
REFRAC
Refractory status 0 = 
Double
1 = Other
Fill on all rows
MMTY
Type of Multiple 
Myeloma
0 = 
Secretory
1= Non-
secretory
When addc.MMYELOTY=SECRETORY, 
MMTY=0
When addc.MMYELOTY= NONSECRETORY, 
MMTY=1
If addc.MMYELOTY is missing, assign 
MMTY=-99
Fill on all rows.
addc
MMIGTY
Myeloma 
immunoglobulin
0 = IGA
1 = IGG
2 = IGM
3 = OTHER
When addc.PARAMCD=MYELOIG and 
AVALC=IGA, then MMIGTY =0
When addc.PARAMCD=MYELOIG and 
AVALC=IGG, then MMIGTY =1
When addc.PARAMCD=MYELOIG and 
AVALC=IGM, then MMIGTY =2
For AVALC which is not equal to IGA/ IGG 
/IGM, then MMIGTY=3
Fill on all rows
addc
BSTAGE
Stage at 
Screening
1 = I
2 = II
3 = III
4 = 
When addc.PARAMCD = STAGESCR and 
AVALC = I, then BSTAGE = 1
When addc.PARAMCD = STAGESCR and 
AVALC = II, then BSTAGE = 2
When addc.PARAMCD = STAGESCR and 
AVALC = III, then BSTAGE = 3
When addc.PARAMCD = STAGESCR and 
AVALC = UNKNOWN or missing , then 
addc


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Column Header
Data Item
Codes
Derivation/Comments
Source 
data set
UNKNOWN 
or missing
BSTAGE = 4
Fill on all rows
For efficacy
General Description:
1.
The dataset is sorted by SUBJID
2.
Three significant figures for all values except those variables which are integers.
3.
Only subjects with CANCER=0 will be included in this dataset as the data for the 
lymphoma patients will not be fully cleaned at the time of the database cut in 4Q2018.
Column 
Header
Data Item
Codes
Derivation/Comments
Source 
data set
C
Line 
number/exclusion 
identifier
Row Number
Set to line/row number
STUDY
Study ID
1 = BMA117159
adsl
SUBJID
Subject identifier 
from source data 
SUBJID = SUBJID
adsl
ID
NONMEM subject 
identifier
Sequential subject identifier across studies 
after data is sorted by SUBJID. Starting with 
derived
PFSCFLCD
PFS Censoring 
Flag Code
0 or 1
For PARAMCD=PFS_D, 
CNSR value is assigned to PFSCFLCD
0=Event
1=Censor
adtte
PFSD
PFS (Days)
For PARAMCD=PFS_D, 
AVAL value is assigned to PFSD
When AVAL is missing for PFS_D, then 
PFSD = -99.
adtte
PFSM
PFS (Months)
For PARAMCD=PFS_M, 
AVAL value is assigned to PFSM
When AVAL is missing for PFS_M, then 
PFSM = -99.
adtte
PFSY
PFS (Years)
For PARAMCD=PFS_D, 
(AVAL/365) value is assigned to PFSY
When AVAL is missing for PFS_Y, then 
PFSY = -99.
derived
TTRCFLCD
TTR Censoring 
Flag Code
0 or 1
For PARAMCD=TTR_D, 
Assign 1 to TTRCFLCD.
For subjects where TTR_D is missing, assign 
0 to TTRCFLCD.
adtte
TTRD
TTR (Days)
For PARAMCD=TTR_D, 
AVAL value is assigned to TTRD.
For subjects where TTR_D is missing, assign 
PFSD to TTRD.
adtte
P


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Column 
Header
Data Item
Codes
Derivation/Comments
Source 
data set
TTRM
TTR (Months)
For PARAMCD=TTR_M, 
AVAL value is assigned to TTRM.
For subjects where TTR_M is missing, assign 
PFSM to TTRM.
adtte
TTRY
TTR (Years)
For PARAMCD=TTR_D, 
(AVAL/365) value is assigned to TTRY.
For subjects where TTR_D is missing, assign 
PFSY to TTRY.
derived
DORCFLCD
DOR Censoring 
Flag Code
0 or 1
For PARAMCD=DOR_D, 
CNSR value is assigned to DORCFLCD
0=Event
1=Censor
Assign “.” for missing.
adtte
DORD
DOR (Days)
For PARAMCD=DOR_D, 
AVAL value is assigned to DORD.
For subjects where DOR_D is missing, 
assign “.”
When TTRCFLCD=0, then DORD = 0
adtte
DORM
DOR (Months)
For PARAMCD=DOR_M, 
AVAL value is assigned to DORM.
For subjects where DOR_M is missing, 
assign “.”
When TTRCFLCD=0, then DORM = 0
adtte
DORY
DOR (Years)
For PARAMCD=DOR_D, 
(AVAL/365) value is assigned to DORY
For subjects where DOR_Y is missing, assign 
“.”
When TTRCFLCD=0, then DORY = 0
derived
ORDRESP
0,1,2,3,4,5,6
For PARAMCD=BCRSP, assign 
0 for PD
1 for SD
2 for MR
3 for PR
4 for VGPR
5 for CR
6 for sCR
adrs
MAXPRED
Obtain AVAL for PARAMCD=MAXPRED.
When AVAL is missing, MAXPRED = -999 
adrs
RESPRATIO
Transform 
MAXRED to a ratio 
to baseline
RESPRATIO = 
max((100+MAXPRED)/100,0.001)

When MAXRED is missing, 
MAXRED = -999 and 
RESPRATIO= -99

When MAXRED is less than -100 
e.g. -100.15, RESPRATIO = 
negative (It is negative but greater 
than -8.99), then update 
RESPRATIO = 0.001 

When MAXRED is equal to -100, 
RESPRATIO = 0, then update 
RESPRATIO = 0.001
adrs,derived
RSPTYP
Response Type
1,2,3
1 for Serum M-Protein
2 for Serum FLC
adrs


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Column 
Header
Data Item
Codes
Derivation/Comments
Source 
data set
3 for Urine M-Protein
CUMAMTP
Cumulative dose to 
progression (mg)
This is needed to derive Time-average AUC 
till progression.
For adtte.PARAMCD=PFS_D,
adex.PARAMCD=ALTDOSE, 
CUMAMTP= Cumulative of adex.AVAL 
starting from adtte.STARTDT and ending at 
adtte.ADT
For progression that occurred on 
dosing days, the dose on the progression day 
was not included in the cumulative dose 
calculation. Here is the code for that:
When adtte.ADT = adex.ASTDT at the last 
dose for that subject, then CUMAMTCT= 
Cumulative of adex.AVAL starting from 
adtte.STARTDT and ending at (adtte.ADT -1)
adex, adtte
TAAUCP 
Time-average AUC 
till progression 
(AUC/day)
The area under the plasma ADC 
concentration–time curve (AUC) per day 
(AUC/day) will be derived for each patient 
using the available ADC dosing information, 
individual patient clearance values from the 
population pharmacokinetic model, and the 
time to the occurrence of the PFS
popPK 
output, 
adtte
CUMAMTR
Cumulative dose to 
Response (mg)
This is needed to derive Time-average AUC 
till response.
For adtte.PARAMCD=TTR_D,
•
adex.PARAMCD=ALTDOSE, 
CUMAMTR= Cumulative of adex.AVAL 
starting from adtte.STARTDT and ending at 
adtte.ADT
•
For response that occurred on 
dosing days, the dose on the response day 
was not included in the cumulative dose 
calculation. Here is the code for that:
When adtte.ADT = adex.ASTDT at the last 
dose for that subject, then CUMAMTCT= 
Cumulative of adex.AVAL starting from 
adtte.STARTDT and ending at (adtte.ADT -1)
When TTRCFLCD=0 ( i.e. subjects who did 
not respond), then CUMAMTR=TOTAMT
adex, adtte
TAAUCR 
Time-average AUC 
till response 
(AUC/day)
The area under the plasma ADC 
concentration–time curve (AUC) per day 
(AUC/day) will be derived for each patient 
using the available ADC dosing information, 
individual patient clearance values from the 
population pharmacokinetic model, and the 
time to the occurrence of the response
popPK 
output, 
adtte
AMT
Amount (in mg) of 
GSK2857916 given 
in first cycle 
AMT = AVAL when PARAMCD=ALTDOSE 
and AVISIT= CYCLE 1 DAY 1
adex
IDOSE
GSK2857916 initial 
cycle dose (mg/kg)
>0
IDOSE=adex.TRT01A; strip off units
adex
CMAX
First dose Cmax of 
PopPK 


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BMA117159
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Column 
Header
Data Item
Codes
Derivation/Comments
Source 
data set
ADC – model 
predicted  EOI 
concentration in 
Cycle 1 (ng/mL)
Individual model predicted conc. at EOI.
output
MMAFCMAX
First dose Cmax. of 
MMAF – model 
predicted 24 
HOURS POST-EOI 
in Cycle 1 (ng/mL)
Individual model predicted conc. at 24 
HOURS POST-EOI in Cycle 1
PopPK 
output
CTAU
First dose Ctau of 
ADC– model 
predicted pre-dose 
concentration Cycle 
2
Individual model predicted pre-dose 
conc.CYCLE 2.
PopPK 
output
AUC
First dose AUC(0-
inf) of ADC 
(ug.day/mL)
First dose (mg)/Individual Clearance of ADC 
(L/Day)
popPK 
output
MMAFAUC
First dose AUC(0-
inf) of MMAF 
(ug.day/mL)
First dose (mg)/Individual Clearance of 
MMAF (L/Day)
popPK 
output
TOTCYC
Total number of 
CYCLES
TOTCYC=AVAL,
AVAL for adex.PARAM=Total Number of 
Cycles
adex
CANCER
Cancer type
0 or 1
0=Multiple Myeloma, 1=BCMA positive 
Lymphomas
If TRT01AN = 12, then CANCER=1, else 
CANCER=0
adsl
ETHN
Subject ethnicity
Same coding 
as CRF/Stats
Fill in ETHN in all rows for each subject
If missing, ETHN = -99
adsl
AGE
Age (years)
Use value as defined by Stats;
adsl
SEX
GENDER
0 or 1
Male = 1
Female = 0
•
If sex is missing, GENDER = -99
adsl
BWT
Baseline Weight 
(kg)
•
Use baseline value as defined by 
Stats in the lab test datasets;  
•
If not defined by Stats, set to weight 
measurement nearest to, but prior to, time of 
first dose
•
Only in cases where Day 1 weight 
is not available, but screening weight is, the 
screening values will be used.
adsl
BECOG 
Baseline ECOG 
status
0
1
2
Fill on all rows
adqs
ECOG 
ECOG status
0
1
2
ECOG is propagated forward from the most 
recent measurement for all observations up 
to the next ECOG measurement (LOCF). 
Please capture the values corresponding to 
the PK time points.
adqs
PRIORRX
Prior line of therapy
When addc.PARAMCD= LTXCPSCR, then 
addc


CONFIDENTIAL
BMA117159
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Column 
Header
Data Item
Codes
Derivation/Comments
Source 
data set
PRIORRX = AVALC (Extract only the number 
and not the text)
For AVALC = MORE THAN 10 LINES, 
PRIORRX=11
Fill on all rows
REFRAC
Refractory status
0 = 
Double
1 = Other
Fill on all rows
MMTY
Type of Multiple 
Myeloma
0 = 
Secretory
1= Non-
secretory
When addc.MMYELOTY=SECRETORY, 
MMTY=0
When addc.MMYELOTY=
NONSECRETORY, MMTY=1
If addc.MMYELOTY is missing, assign 
MMTY=-99
Fill on all rows.
addc
MMIGTY
Myeloma 
immunoglobulin
0 = IGA
1 = IGG
2 = IGM
3 = OTHER
When addc.PARAMCD=MYELOIG and 
AVALC=IGA, then MMIGTY =0
When addc.PARAMCD=MYELOIG and 
AVALC=IGG, then MMIGTY =1
When addc.PARAMCD=MYELOIG and 
AVALC=IGM, then MMIGTY =2
For AVALC which is not equal to IGA/ IGG 
/IGM, then MMIGTY=3
Fill on all rows
addc
BSTAGE
Stage at Screening
1 = I
2 = II
3 = III
4 = 
UNKNOWN 
or missing
When addc.PARAMCD = STAGESCR and 
AVALC = I, then BSTAGE = 1
When addc.PARAMCD = STAGESCR and 
AVALC = II, then BSTAGE = 2
When addc.PARAMCD = STAGESCR and 
AVALC = III, then BSTAGE = 3
When addc.PARAMCD = STAGESCR and 
AVALC = UNKNOWN or missing , then 
BSTAGE = 4
Fill on all rows
addc
16.10.2.
Pharmacokinetic / Pharmacodynamic Methodology
The primary goal of this analysis is to characterize the 
pharmacokinetic/pharmacodynamic relationships for GSK2857916 administered IV in 
subjects with multiple myeloma, data permitting.  In these analyses, drug plasma 
concentration (or pharmacokinetic parameter) data and pharmacodynamic data will be 
subjected to logistic regression and time-to-event analyses, as appropriate, using suitable 
software.  The influence of subject demographics and baseline characteristics, including 


CONFIDENTIAL
BMA117159
126
disease activity, in this population may be investigated.  This analysis will be performed 
by CPMS and reported separately.
16.10.2.1. Exposure-Response Analyses
16.10.2.1.1.
Corneal Events
Presence or absence of corneal events will be described using a conventional logistic 
regression model for both Grade 1 and Grade 2 toxicity. Time to first corneal event 
will be explored using Kaplan Meier plots categorized by exposure measures. Severity of 
corneal event will be analyzed using an ordered logistic regression model assuming 
Grades 0 (no toxicity), 1, 2 and 3, with exposure subdivided into quartiles and quintiles.
16.10.2.1.2.
Clinical Response
Presence or absence of clinical response will be described using a conventional logistic 
regression model. Time to response will be explored using Kaplan Meier plots 
categorized by exposure measures.
PFS will be explored using Kaplan Meier plots categorized by exposure measures and 
occurrence of progression may also be described using a conventional logistic regression 
model.
Duration of response will be explored using Kaplan Meier plots categorized by exposure 
measures. 
Best clinical response will be analyzed using an ordered logistic regression, with 
response categorized from 0 (progressive disease) to 6 (stringent complete response). 
Exposure will be treated as a categorical variable subdivided into quartiles and quintiles.  
In the ordered logistic regression analyses, the use of categorical measures of exposure in 
lieu of continuous variables will allow for non-parametric descriptions of response 
functions.
Best clinical response as assessed by maximum reduction in M-protein or FLC will be 
analyzed by exposure (continuous and/or categorized by exposure measures).


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16.11.
Appendix 11: Abbreviations & Trade Marks
16.11.1.
Abbreviations
Abbreviation
Description
ADaM
Analysis Data Model
AE
Adverse Event
Ae(0-t)
Amount of drug excreted in urine from dosing to time t
AIC
Akaike's Information Criteria
A&R
Analysis and Reporting 
AUC
Area under the concentration-time curve
CDISC
Clinical Data Interchange Standards Consortium
CI
Confidence Interval
CPMS
Clinical Pharmacology Modelling & Simulation
CR
Complete response
CS
Clinical Statistics
CSR
Clinical Study Report
CTR
Clinical Trial Register
CVb / CVw
Coefficient of Variation (Between) / Coefficient of Variation (Within)
DBF
Database Freeze
DBR
Database Release
CBR
Clinical benefit rate
CDISC
Clinical Data Interchange Standards Consortium
CI
Confidence interval
CK-MB
Creatine kinase MB-isoenzyme
CL
Clearance
Cmax
Maximum observed plasma drug concentration
CPMS
Clinical Pharmacology Modeling and Simulation
CR
Complete response
CRM
Continual Reassessment Method
Ctrough
Concentration observed prior to the next dose
Cys-mcMMAF
Cysteine-maleimidocaproyl monomethyl auristatin F 
DLT
Dose limiting toxicity
DOB
Date of Birth
DOR
Duration of response
DP
Decimal Places
eDiary
Electronic Diary
ECOG
Eastern Cooperative Oncology Group
EOI
End of infusion
eCRF
Electronic Case Record Form
EMA
European Medicines Agency
FACTS
Fixed and adapted clinical trials simulator
FDA
Food and Drug Administration
FDAAA
Food and Drug Administration Clinical Results Disclosure Requirements
Fe(0-t)
Fraction of administered dose excreted in urine from dosing to time t
FLC
Free light chain


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Abbreviation
Description
FTIH
First time in human
GSK
GlaxoSmithKline
IA
Interim Analysis
ICH
International Conference on Harmonization
IDMC
Independent Data Monitoring Committee 
IDSL
Integrated Data Standards Library
IMMS
International Modules Management System
IP
Investigational Product
ITT
Intent-To-Treat
LDH
Lactate dehydrogenase
MMRM
Mixed Model Repeated Measures
MM
Multiple Myeloma
MMAF
Monomethyl auristatin F
MR
Minimal response
MTD
Maximum Tolerated Dose
NCI-CTCAE
National Cancer Institute – Common Terminology Criteria for Adverse Events
N-CRM
A modification of the Continual Reassessment Method (CRM) proposed by 
Neuenschwander et al.
NEI-VFQ-25
National Eye Institute Visual Functioning Questionnaire - 25
NONMEM
Nonlinear mixed effects modelling
ORR
Overall response rate
OS
Overall survival
OSDI
Ocular Surface Disease Index
PCI
Potential Clinical Importance 
PD
Pharmacodynamics
PD
Progressive disease
PDMP
Protocol Deviation Management Plan
PET
Probability of early termination
PFS
Progression-free survival
PK
Pharmacokinetics
PP
Per Protocol
PR
Partial response
PopPK
Population PK
QC
Quality Control
QoL
Quality of life
QTcF
Fridericia’s QT Interval Corrected for Heart Rate
QTcB
Bazett’s QT Interval Corrected for Heart Rate
RAP
Reporting & Analysis Plan
RAMOS
Randomization & Medication Ordering System 
REML
Restricted maximum likelihood
Ro
Observed accumulation ratio
RP2
Recommended Phase 2 
SAC
Statistical Analysis Complete
SAE
Serious adverse event
sBCMA
Soluble B-cell maturation antigen


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Abbreviation
Description
sCR
Stringent complete response
SD
Stable disease
SDSP
Study Data Standardization Plan
SDTM
Study Data Tabulation Model
SOI
Start of infusion
SPEP
Serum protein electrophoresis
SOP
Standard Operation Procedure
t½ 
Terminal phase half-life
TA
Therapeutic Area
TFL
Tables, Figures & Listings 
tlast
Time of last quantifiable concentration
tmax
Time to maximum drug concentration
TTBR
Time to best response
TTP
Time to progression
TTR
Time to response
ULN
Upper limit of normal
UPEP
Urine protein electrophoresis
VGPR
Very good partial response
Vss
Volume of distribution at steady state
16.11.2.
Trademarks
Trademarks of the GlaxoSmithKline 
Group of Companies
Trademarks not owned by the 
GlaxoSmithKline Group of Companies
NONE
FACTS
NONMEM
SAS
WinNonlin


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16.12.
Appendix 12: List of Data Displays
16.12.1.
Data Display Numbering
The following numbering will be applied for RAP generated displays:
Section
Tables
Figures
Study Population
1.0010 to 1.xxxx
11.0010 to 11.xxxx
Efficacy
2.0010 to 2.xxxx
12.0010 to 12.xxxx
Safety
3.0010 to 3.xxxx
13.0010 to 13.xxxx
Pharmacokinetic
4.0010 to 4.xxxx
14.0010 to 14.xxxx
Population Pharmacokinetic (PopPK)
5.0010 to 5.xxxx
15.0010 to 15.xxxx
Pharmacodynamic and / or Biomarker
6.0010 to 6.xxxx
16.0010 to 16.xxxx
Pharmacokinetic / Pharmacodynamic
7.0010 to 7.xxxx
17.0010 to 17.xxxx
Section
Listings
ICH Listings
1.0010 to 1.xxxx
Other Listings
30.0010 to 30.xxxx
16.12.2.
Mock Example Shell Referencing
Non IDSL specifications will be referenced as indicated and if required example mock-up 
displays provided in Appendix 13: Example Mock Shells for Data Displays.
Section
Figure
Table
Listing
Study Population
POP_Fn
POP_Tn
POP_Ln
Efficacy
EFF_Fn
EFF_Tn
EFF_Ln
Safety
SAFE_Fn
SAFE_Tn
SAFE_Ln
Pharmacokinetic
PK_Fn
PK_Tn
PK_Ln
Population Pharmacokinetic (PopPK)
POPPK_Fn
POPPK_Tn
POPPK_Ln
Pharmacodynamic and / or Biomarker
PD_Fn
PD_Tn
PD_Ln
Pharmacokinetic / Pharmacodynamic
PKPD_Fn
PKPD_Tn
PK/PD_Ln
NOTES: 

Non-Standard displays are indicated in the ‘IDSL /  Example Shell’ or ‘Programming Notes’ column as ‘[Non-
Standard] + Reference.’
16.12.3.
Deliverables
Delivery [Priority] [1]
Description
DS [X]
During Study
DE [X]
Dose Escalation
IA SAC [X]
Interim Analysis Statistical Analysis Complete
SAC [X]
Final Statistical Analysis Complete
NOTES: 
1.
Indicates priority (i.e. order) in which displays will be generated for the reporting effort.


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16.12.4.
Study Population Tables
Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Subject Disposition
1.0010
All Treated
ES8
Summary of Subject Status and Reason for Study Withdrawal 
(Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0011
All Treated
ES8
Summary of Subject Status and Reason for Study Withdrawal 
(Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0012
All Treated
ES8
Summary of Subject Status and Reason for Study Withdrawal 
(All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0013
All Treated
ES8
Summary of Subject Status and Reason for Study Withdrawal 
(Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
1.0020
All Treated
SD4
Summary of Treatment Status and Reasons for Discontinuation 
of Study Treatment (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0021
All Treated
SD4
Summary of Treatment Status and Reasons for Discontinuation 
of Study Treatment (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0022
All Treated
SD4
Summary of Treatment Status and Reasons for Discontinuation 
of Study Treatment (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0023
All Treated
SD4
Summary of Treatment Status and Reasons for Discontinuation 
of Study Treatment (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
1.0030
Enrolled
NS1
Summary of Number of Participant by Country and Site ID (MM)
Include columns: No Treatment, 
Part 1, Part 2 MM, All Treated MM, 
Total column will be the subjects 
enrolled to MM cohort. Add a 
footnote: This summary is based on 
all subjects enrolled into multiple 
SAC [A]


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Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
myeloma cohorts.
1.0031
Enrolled
NS1
Summary of Number of Participant by Country and Site ID (NHL)
Include columns: No Treatment, 
Part 2 NHL, Total column will be the 
subjects enrolled to NHL cohort. 
Add a footnote: This summary is 
based on all subjects enrolled into 
lymphoma cohorts.
SAC
1.0050
All Treated
IE1
Summary of Inclusion/Exclusion Criteria Deviations (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0051
All Treated
IE1
Summary of Inclusion/Exclusion Criteria Deviations (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0052
All Treated
IE1
Summary of Inclusion/Exclusion Criteria Deviations (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0053
All Treated
IE1
Summary of Inclusion/Exclusion Criteria Deviations (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC


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Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Protocol Deviation
1.0040
All Treated
DV1
Summary of Important Protocol Deviations (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0041
All Treated
DV1
Summary of Important Protocol Deviations (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0042
All Treated
DV1
Summary of Important Protocol Deviations (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0043
All Treated
DV1
Summary of Important Protocol Deviations (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
Population Analysed
1.0060
Enrolled
SP1
Summary of Study Populations (MM)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total). This 
table is based on subjects enrolled 
to MM, we do not have screen 
failure data, hence no screened 
population. For columns, include No 
Treatment, No Treatment for Part 1, 
No Treatment for Part 2 MM, Dose 
levels in part 1, All Treated in Part 
1, All Treated in Part 2, All Treated 
and Total. 
Rows: include Enrolled, Part 1, Part 
2 MM, All Treated MM, DLT 
Evaluable, PK, PD
SAC [A]
1.0061
Enrolled
SP1
Summary of Study Populations (NHL)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). This table is 
SAC


CONFIDENTIAL
BMA117159
134
Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
based on subjects enrolled to NHL, 
we do not have screen failure data, 
hence no screened population. For 
columns, include No Treatment, All 
Treated and Total. 
Rows: include Enrolled, Part 2 NHL, 
PK, PD
1.0430
Enrolled
SP2A
Summary of the Exclusions from the Part 1 Population
SAC [A]
1.0431
Enrolled
SP2A
Summary of the Exclusions from the Part 2 MM Population
SAC [A]
1.0432
Enrolled
SP2A
Summary of the Exclusions from the All Treated MM Population
SAC [A]
1.0433
Enrolled
SP2A
Summary of the Exclusions from the Part 2 NHL Population
SAC [A]
1.0434
Enrolled
SP2A
Summary of the Exclusions from the All Treated Population
SAC [A]
1.0435
Enrolled
SP2A
Summary of the Exclusions from the DLT Evaluable Population 
SAC [A]
1.0436
Enrolled
SP2A
Summary of the Exclusions from the Pharmacokinetic (PK) 
Population 
SAC [A]
1.0437
Enrolled
SP2A
Summary of the Exclusions from the Pharmacodynamic (PD) 
Population 
SAC [A]
Demographic and Baseline Characteristics
1.0070
All Treated
DM1
Summary of Demographic Characteristics (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0071
All Treated
DM1
Summary of Demographic Characteristics (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0072
All Treated
DM1
Summary of Demographic Characteristics (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]


CONFIDENTIAL
BMA117159
135
Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0073
All Treated
DM1
Summary of Demographic Characteristics (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
1.0290
Enrolled
DM11
Summary of Age Ranges (MM)
Include columns "No Treatment", 
"Part 1", "Part 2 MM", "All Treated 
MM", "Total"
SAC [A]
1.0291
Enrolled
DM11
Summary of Age Ranges (NHL)
Include columns "No Treatment", 
"Part 2 NHL", "Total"
SAC
1.0080
All Treated
DM5
Summary of Race and Racial Combinations (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0081
All Treated
DM5
Summary of Race and Racial Combinations (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0082
All Treated
DM5
Summary of Race and Racial Combinations (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0083
All Treated
DM5
Summary of Race and Racial Combinations (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
1.0090
All Treated
DM6
Summary of Race and Racial Combination Details (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0091
All Treated
DM6
Summary of Race and Racial Combination Details (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0092
All Treated
DM6
Summary of Race and Racial Combination Details (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0093
All Treated
DM6
Summary of Race and Racial Combination Details (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC


CONFIDENTIAL
BMA117159
136
Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Prior and Concomitant Medications
1.0190
All Treated
MH1
Summary of Past Medical Conditions (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0191
All Treated
MH1
Summary of Past Medical Conditions (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0192
All Treated
MH1
Summary of Past Medical Conditions (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0193
All Treated
MH1
Summary of Past Medical Conditions (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
1.0200
All Treated
MH1
Summary of Current Medical Conditions (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0201
All Treated
MH1
Summary of Current Medical Conditions (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0202
All Treated
MH1
Summary of Current Medical Conditions (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0203
All Treated
MH1
Summary of Current Medical Conditions (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
1.0210
All Treated
CM8
Summary of Concomitant Medications  (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0211
All Treated
CM8
Summary of Concomitant Medications (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0212
All Treated
CM8
Summary of Concomitant Medications (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0213
All Treated
CM8
Summary of Concomitant Medications (Part 2 NHL)
Report for: Part 2 NHL, 
SAC


CONFIDENTIAL
BMA117159
137
Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
(Summarize: only for 3.4 NHL).
1.0380
All Treated
CM1
Summary of Prophylactic Medication for Infusion-Related 
Reactions by Drug Class and Drug Name (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). Please 
replace ATC Level 1 by ‘Drug Class’ 
and ‘Ingredient’ by ‘Drug’. Replace 
the footnote as “Subjects may be 
included in more than one category 
for ‘Drug Class' and ‘Drug'.
SAC [A]
1.0381
All Treated
CM1
Summary of Prophylactic Medication for Infusion-Related 
Reactions by Drug Class and Drug Name (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Please replace 
ATC Level 1 by ‘Drug Class’ and 
‘Ingredient’ by ‘Drug’. Replace the 
footnote as “Subjects may be 
included in more than one category 
for ‘Drug Class' and ‘Drug'.
SAC [A]
1.0382
All Treated
CM1
Summary of Prophylactic Medication for Infusion-Related 
Reactions by Drug Class and Drug Name (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Please replace 
ATC Level 1 by ‘Drug Class’ and 
‘Ingredient’ by ‘Drug’. Replace the 
footnote as “Subjects may be 
included in more than one category 
for ‘Drug Class' and ‘Drug'.
SAC [A]
1.0383
All Treated
CM1
Summary of Prophylactic Medication for Infusion-Related 
Reactions by Drug Class and Drug Name (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
Please replace ATC Level 1 by 
‘Drug Class’ and ‘Ingredient’ by 
‘Drug’. Replace the footnote as 
“Subjects may be included in more 
SAC


CONFIDENTIAL
BMA117159
138
Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
than one category for ‘Drug Class' 
and ‘Drug'.
1.0510
All Treated
OSP2
Summary of Prior Cancer and Non-Cancer Related Surgical 
Procedures (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). If the 
CRF does not have any coded 
procedures and collection of 
surgeries is restricted to prior 
cancer related surgeries, then a 
summary is not necessary as the 
number and percent of subjects with 
surgeries will be provided in the 
anticancer therapy display (see 
Example AC1).  Otherwise a 
simplified version of the summary 
can be utilized if appropriate (see 
example OSP2).  
SAC [A]
1.0511
All Treated
OSP2
Summary of Prior Cancer and Non-Cancer Related Surgical 
Procedures (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0512
All Treated
OSP2
Summary of Prior Cancer and Non-Cancer Related Surgical 
Procedures (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0513
All Treated
OSP2
Summary of Prior Cancer and Non-Cancer Related Surgical 
Procedures (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
Exposure and Treatment Compliance
1.0240
All Treated
OEX5
Summary of Exposure to GSK2857916 (Part 1)
Report for population: Part 1, 
(Summarize: by ascending dose 
level, Total).
Do not need "Dose Intensity " 
SAC [A]


CONFIDENTIAL
BMA117159
139
Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
section. Use 4, <4, >4 cycles
1.0241
All Treated
OEX5
Summary of Exposure to GSK2857916 (Part 2 MM)
Report for population: Part 2 MM, 
(Summarize: only for 3.4 MM). 
Do not need "Dose Intensity " 
section. Use 4, <4, >4 cycles
SAC [A]
1.0242
All Treated
OEX5
Summary of Exposure to GSK2857916 (All Treated MM)
Report for population: All Treated 
MM, (Summarize: Total)
Do not need "Dose Intensity "
section. Use 4, <4, >4 cycles
SAC [A]
1.0243
All Treated
OEX5
Summary of Exposure to GSK2857916 (Part 2 NHL)
Report for population: 3.4 NHL, 
(Summarize: Total)
Do not need "Dose Intensity " 
section. Use 4, <4, >4 cycles
SAC
1.0230
All Treated
OEX6
Summary of Dose Intensity of GSK2857916 by Cycle (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total). Dose 
Intensity(mg/kg/cycle)
SAC [A]
1.0231
All Treated
OEX6
Summary of Dose Intensity of GSK2857916 by Cycle (Part 2 
MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Dose 
Intensity(mg/kg/cycle)
SAC [A]
1.0232
All Treated
OEX6
Summary of Dose Intensity of GSK2857916 by Cycle (All 
Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Dose 
Intensity(mg/kg/cycle)
SAC [A]
1.0233
All Treated
OEX6
Summary of Dose Intensity of GSK2857916 by Cycle (Part 2 
NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL). 
Dose Intensity(mg/kg/cycle)
SAC


CONFIDENTIAL
BMA117159
140
Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0250
All Treated
ODMOD
1
Summary of Dose Reductions of GSK2857916 (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0251
All Treated
ODMOD
1
Summary of Dose Reductions of GSK2857916 (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0252
All Treated
ODMOD
1
Summary of Dose Reductions of GSK2857916 (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0253
All Treated
ODMOD
1
Summary of Dose Reductions of GSK2857916 (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
1.0260
All Treated
ODMOD
3
Summary of Dose Delays of GSK2857916 (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0261
All Treated
ODMOD
3
Summary of Dose Delays of GSK2857916 (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0262
All Treated
ODMOD
3
Summary of Dose Delays of GSK2857916 (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0263
All Treated
ODMOD
3
Summary of Dose Delays of GSK2857916 (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
1.0270
All Treated
ODMOD
5
Summary of Primary Reason for Dose Reductions of 
GSK2857916 by Cycle (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0271
All Treated
ODMOD
5
Summary of Primary Reason for Dose Reductions of 
GSK2857916 by Cycle (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0272
All Treated
ODMOD
5
Summary of Primary Reason for Dose Reductions of 
GSK2857916 by Cycle (All Treated MM)
Report for: All Treated MM,
(Summarize: Total).
SAC [A]
1.0273
All Treated
ODMOD
5
Summary of Primary Reason for Dose Reductions of 
GSK2857916 by Cycle (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC


CONFIDENTIAL
BMA117159
141
Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0280
All Treated
ODMOD
6
Summary of Primary Reason for Dose Delays of GSK2857916 
by Cycle (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0281
All Treated
ODMOD
6
Summary of Primary Reason for Dose Delays of GSK2857916 
by Cycle (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0282
All Treated
ODMOD
6
Summary of Primary Reason for Dose Delays of GSK2857916 
by Cycle (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0283
All Treated
ODMOD
6
Summary of Primary Reason for Dose Delays of GSK2857916 
by Cycle (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
Disease Characteristics
1.0100
All Treated
DC2
Summary of Disease Characteristics at Screening (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total). 
Summarize Stage (I, II, III, 
Unknown, Missing), 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, IgG, Other, Missing)
SAC [A]
1.0101
All Treated
DC2
Summary of Disease Characteristics at Screening (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Summarize 
categories as defined in Table
1,0100.
SAC [A]


CONFIDENTIAL
BMA117159
142
Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0102
All Treated
DC2
Summary of Disease Characteristics at Screening (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total). Summarize 
categories as defined in Table 
1,0100.
SAC [A]
1.0103
All Treated
DC2
Summary of Disease Characteristics at Screening (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
1.0110
All Treated
POP_T1
Summary of Genetic Characteristics at Screening (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0111
All Treated
POP_T1
Summary of Genetic Characteristics at Screening (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0112
All Treated
POP_T1
Summary of Genetic Characteristics at Screening (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0300
All Treated
DC1
Summary of Disease Characteristics at Initial Diagnosis (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total). 
Include alll optional columns.
SAC [A]
1.0301
All Treated
DC1
Summary of Disease Characteristics at Initial Diagnosis (Part 2 
MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Include all optional 
columns.
SAC [A]
1.0302
All Treated
DC1
Summary of Disease Characteristics at Initial Diagnosis (All 
Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Include all 
optional columns.
SAC [A]
1.0303
All Treated
DC1
Summary of Disease Characteristics at Initial Diagnosis (Part 2 
NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL). 
Include all optional columns.
SAC


CONFIDENTIAL
BMA117159
143
Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0390
All Treated
POP_T2
Summary of Cytogenetics Risk at Screening (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0391
All Treated
POP_T2
Summary of Cytogenetics Risk at Screening (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0392
All Treated
POP_T2
Summary of Cytogenetics Risk at Screening (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
Prior and Follow-up Anti-Cancer Therapy
1.0120
All Treated
AC1
Summary of Prior Anti-Cancer Therapy (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0121
All Treated
AC1
Summary of Prior Anti-Cancer Therapy (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0122
All Treated
AC1
Summary of Prior Anti-Cancer Therapy (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0123
All Treated
AC1
Summary of Prior Anti-Cancer Therapy (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
1.0130
All Treated
CM8
Summary of Prior Dictionary Coded Anti-Cancer Therapy (Part 
1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0131
All Treated
CM8
Summary of Prior Dictionary Coded Anti-Cancer Therapy (Part 2 
MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0132
All Treated
CM8
Summary of Prior Dictionary Coded Anti-Cancer Therapy (All 
Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0133
All Treated
CM8
Summary of Prior Dictionary Coded Anti-Cancer Therapy (Part 2 
NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC


CONFIDENTIAL
BMA117159
144
Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0140
All Treated
POP_T3
Summary of Prior Anti-Cancer Therapy by Drug Class of Agents 
(Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0141
All Treated
POP_T3
Summary of Prior Anti-Cancer Therapy by Drug Class of Agents 
(Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0142
All Treated
POP_T3
Summary of Prior Anti-Cancer Therapy by Drug Class of Agents 
(All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0150
All Treated
POP_T4
Summary of Subjects Refractory to Prior Anti-Cancer Therapy 
by Drug Class of Agents (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0151
All Treated
POP_T4
Summary of Subjects Refractory to Prior Anti-Cancer Therapy 
by Drug Class of Agents (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0152
All Treated
POP_T4
Summary of Subjects Refractory to Prior Anti-Cancer Therapy 
by Drug Class of Agents (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0160
All Treated
AC3
Summary of Number of Prior Anti-Cancer Therapy Regimens 
(Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total). 
Therapies should be sorted in 
highest to lowest incidence. Include 
radio therapy and surgical 
procedures.
SAC [A]
1.0161
All Treated
AC3
Summary of Number of Prior Anti-Cancer Therapy Regimens 
(Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Therapies should 
be sorted in highest to lowest 
incidence. Include radio therapy and 
surgical procedures.
SAC [A]
1.0162
All Treated
AC3
Summary of Number of Prior Anti-Cancer Therapy Regimens 
(All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Therapies 
should be sorted in highest to 
SAC [A]


CONFIDENTIAL
BMA117159
145
Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
lowest incidence. Include radio 
therapy and surgical procedures.
1.0163
All Treated
AC3
Summary of Number of Prior Anti-Cancer Therapy Regimens 
(Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL). 
Therapies should be sorted in 
highest to lowest incidence. Include 
radio therapy and surgical 
procedures.
SAC
1.0170
All Treated
AC4
Summary of Best Response to Most Recent Prior Anti-Cancer 
Therapy (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total). Only 
use last therapy prior to starting 
study, 
SAC [A]
1.0171
All Treated
AC4
Summary of Best Response to Most Recent Prior Anti-Cancer 
Therapy (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Only use last 
therapy prior to starting study
SAC [A]
1.0172
All Treated
AC4
Summary of Best Response to Most Recent Prior Anti-Cancer 
Therapy (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Only use last 
therapy prior to starting study
SAC [A]
1.0173
All Treated
AC4
Summary of Best Response to Most Recent Prior Anti-Cancer 
Therapy (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
1.0470
All Treated
FAC1
Summary of Follow-Up Anti-Cancer Therapy (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0471
All Treated
FAC1
Summary of Follow-Up Anti-Cancer Therapy (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0472
All Treated
FAC1
Summary of Follow-Up Anti-Cancer Therapy (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]


CONFIDENTIAL
BMA117159
146
Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0473
All Treated
FAC1
Summary of Follow-Up Anti-Cancer Therapy (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
Duration of Follow-up 
1.0310
All Treated
FAC2
Summary of Duration of Follow-up (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total). 
Include all optional columns.
SAC [A]
1.0311
All Treated
FAC2
Summary of Duration of Follow-up (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Include all optional 
columns.
SAC [A]
1.0312
All Treated
FAC2
Summary of Duration of Follow-up (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Include al 
optional columns.
SAC [A]
1.0313
All Treated
FAC2
Summary of Duration of Follow-up (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL). 
Include all optional columns.
SAC
1.0400
All Treated
FAC2
Summary of Duration of Follow-up for Subjects with Prior 
Daratumumab Treatment and Refractory to Both 
Immunomodulators and Proteasome Inhibitors (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0401
All Treated
FAC2
Summary of Duration of Follow-up for Subjects with Prior 
Daratumumab Treatment and Refractory to Both 
Immunomodulators and Proteasome Inhibitors (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0402
All Treated
FAC2
Summary of Duration of Follow-up for Subjects with Prior 
Daratumumab Treatment and Refractory to Both 
Immunomodulators and Proteasome Inhibitors (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0410
All Treated
FAC2
Summary of Duration of Follow-up for Subjects without Prior 
Report for:  Part 1, (Summarize: by 
SAC [A]


CONFIDENTIAL
BMA117159
147
Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Daratumumab Treatment (Part 1)
ascending dose level, Total).
1.0411
All Treated
FAC2
Summary of Duration of Follow-up for Subjects without Prior 
Daratumumab Treatment (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0412
All Treated
FAC2
Summary of Duration of Follow-up for Subjects without Prior 
Daratumumab Treatment (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0420
All Treated
FAC2
Summary of Duration of Follow-up for Subjects Refractory to 
Both Immunomodulators and Proteasome Inhibitors (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0421
All Treated
FAC2
Summary of Duration of Follow-up for Subjects Refractory to 
Both Immunomodulators and Proteasome Inhibitors (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0422
All Treated
FAC2
Summary of Duration of Follow-up for Subjects Refractory to 
Both Immunomodulators and Proteasome Inhibitors (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
Blood and Blood Supportive Care Products
1.0480
All Treated
BP1A
Summary of Blood Products (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0481
All Treated
BP1A
Summary of Blood Products (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0482
All Treated
BP1A
Summary of Blood Products (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0483
All Treated
BP1A
Summary of Blood Products (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
1.0490
All Treated
BP1C
Summary of Blood Supportive Care Products (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0491
All Treated
BP1C
Summary of Blood Supportive Care Products (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
SAC [A]


CONFIDENTIAL
BMA117159
148
Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
only for 3.4 MM).
1.0492
All Treated
BP1C
Summary of Blood Supportive Care Products (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0493
All Treated
BP1C
Summary of Blood Supportive Care Products (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
Substance Use
1.0500
All Treated
SU1
Summary of Substance Use (Part 1)
Report for
:  Part 1, (Summarize: by ascending 
dose level, Total). All substance 
collected in eCRF
SAC [A]
1.0501
All Treated
SU1
Summary of Substance Use (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). All substance 
collected in eCRF
SAC [A]
1.0502
All Treated
SU1
Summary of Substance Use (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). All substance 
colleced in eCRF
SAC [A]
1.0503
All Treated
SU1
Summary of Substance Use (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL). All 
substance colleced in eCRF
SAC
NOTES: 
A. Indicates which displays will be generated for the reporting effort for multiple myeloma


CONFIDENTIAL
BMA117159
149
16.12.5.
Study Population Figures
Study Population: Figures
No.
Population
IDSL /  
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Exposure
11.0020
All Treated
POP_F2
Plot of Dose Reduction of GSK2857916 by Cycle (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Combine 1.9 mg/kg and 
1.7 mg/kg dose groups as 1.7 
mg/kg. Sort the bar by descending 
dose levels. Add foot note "Doses 
1.9 mg/kg and 1.7 mg/kg are 
combined and represented by 1.7 
mg/kg." 
SAC [A]
11.0030
All Treated
OEX12
Plot of Duration of Study Treatment by Response (Part 1)
Report for population subgroup: 
Part 1. Y axis: dose cohort. Use 
best confirmed response. Please 
add the footnote regarding 
treatment duration consistent with 
the one in OEX12.
SAC [A]
11.0031
All Treated
OEX12
Plot of Duration of Study Treatment by Response (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Y axis: dose cohort. Use 
best confirmed response. Please 
add the footnote regarding 
treatment duration consistent with 
the one in OEX12.
SAC [A]
11.0032
All Treated
OEX12
Plot of Duration of Study Treatment by Response (All Treated 
MM)
Report for population subgroup: All 
Treated MM. Y axis: dose cohort. 
Use best confirmed response. 
Please add the footnote regarding 
SAC [A]


CONFIDENTIAL
BMA117159
150
Study Population: Figures
No.
Population
IDSL /  
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
treatment duration consistent with 
the one in OEX12.
NOTES: 
A. Indicates which displays will be generated for the reporting effort for multiple myeloma
16.12.6.
Efficacy Tables
Efficacy: Tables
No.
Populati
on
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Response
2.0020
All 
Treated
RE1a
Summary of Investigator-Assessed Best Response (With 
Confirmation) (IMWG 2011) (Part 1)
Report for population subgroup: 
Part 1. Summarize by dose level; 
Do not include Total.
Best Response: Stringent Complete 
Response (sCR), Complete 
response (CR), Very Good Partial 
Response (VGPR), Partial 
Response (PR), Minimal Response 
(MR), Stable Disease (SD), 
Progressive Disease (PD), Not 
Evaluable (NE).
Overall Response Rate: 
(sCR+CR+VGPR+PR).
Clinical Benefit Rate: 
SAC [A]


CONFIDENTIAL
BMA117159
151
Efficacy: Tables
No.
Populati
on
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
(sCR+CR+VGPR+PR+MR).
Include: Overall Response Rate and 
Clinical Benefit Rate (No p-value) in 
one table. Footnote: The 95% 
Confidence Interval is based on 
Exact method.
2.0021
All 
Treated
RE1a
Summary of Investigator-Assessed Best Response (With 
Confirmation) (IMWG 2011) (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize for 3.4 MM.
Best Response: Stringent Complete 
Response (sCR), Complete 
response (CR), Very Good Partial 
Response (VGPR), Partial 
Response (PR), Minimal Response 
(MR), Stable Disease (SD), 
Progressive Disease (PD), Not 
Evaluable (NE).
Overall Response Rate: 
(sCR+CR+VGPR+PR).
Clinical Benefit Rate: 
(sCR+CR+VGPR+PR+MR).
Include: Overall Response Rate and 
Clinical Benefit Rate (No p-value) in 
one table.
SAC [A]
2.0180
All 
Treated
RE1a
Summary of Investigator-Assessed Best Response (With 
Confirmation) for Subjects with Prior Daratumumab Treatment 
and Refractory to Both Immunomodulators and Proteasome
Inhibitors (IMWG 2011) (Part 1)
Report for population subgroup: 
Part 1. Summarize by dose level; 
Do not include Total.
Best Response: Stringent Complete 
Response (sCR), Complete 
SAC [A]


CONFIDENTIAL
BMA117159
152
Efficacy: Tables
No.
Populati
on
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
response (CR), Very Good Partial 
Response (VGPR), Partial 
Response (PR), Minimal Response 
(MR), Stable Disease (SD), 
Progressive Disease (PD), Not 
Evaluable (NE).
Overall Response Rate: 
(sCR+CR+VGPR+PR).
Clinical Benefit Rate: 
(sCR+CR+VGPR+PR+MR).
Include: Overall Response Rate and 
Clinical Benefit Rate (No p-value) in 
one table.
2.0181
All 
Treated
RE1a
Summary of Investigator-Assessed Best Response (With 
Confirmation) for Subjects with Prior Daratumumab Treatment 
and Refractory to Both Immunomodulators and Proteasome
Inhibitors (IMWG 2011) (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize for 3.4 MM.
Best Response: Stringent Complete 
Response (sCR), Complete 
response (CR), Very Good Partial 
Response (VGPR), Partial 
Response (PR), Minimal Response 
(MR), Stable Disease (SD), 
Progressive Disease (PD), Not 
Evaluable (NE).
Overall Response Rate: 
(sCR+CR+VGPR+PR).
Clinical Benefit Rate: 
(sCR+CR+VGPR+PR+MR).
Include: Overall Response Rate and 
SAC [A]


CONFIDENTIAL
BMA117159
153
Efficacy: Tables
No.
Populati
on
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Clinical Benefit Rate (No p-value) in 
one table.
2.0110
All 
Treated
RE1a
Summary of Investigator-Assessed Best Response (With 
Confirmation) for Subjects without Prior Daratumumab 
Treatment (IMWG 2011) (Part 1)
Report for population subgroup: 
Part 1. Summarize by dose level; 
Do not include Total.
Best Response: Stringent Complete 
Response (sCR), Complete 
response (CR), Very Good Partial 
Response (VGPR), Partial 
Response (PR), Minimal Response 
(MR), Stable Disease (SD), 
Progressive Disease (PD), Not 
Evaluable (NE).
Overall Response Rate: 
(sCR+CR+VGPR+PR).
Clinical Benefit Rate: 
(sCR+CR+VGPR+PR+MR).
Include: Overall Response Rate and 
Clinical Benefit Rate (No p-value) in 
one table.
SAC [A]
2.0111
All 
Treated
RE1a
Summary of Investigator-Assessed Best Response (With 
Confirmation) for Subjects without Prior Daratumumab 
Treatment (IMWG 2011) (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize for 3.4 MM.
Best Response: Stringent Complete 
Response (sCR), Complete 
response (CR), Very Good Partial 
Response (VGPR), Partial 
Response (PR), Minimal Response 
(MR), Stable Disease (SD), 
SAC [A]


CONFIDENTIAL
BMA117159
154
Efficacy: Tables
No.
Populati
on
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Progressive Disease (PD), Not 
Evaluable (NE).
Overall Response Rate: 
(sCR+CR+VGPR+PR).
Clinical Benefit Rate: 
(sCR+CR+VGPR+PR+MR).
Include: Overall Response Rate and 
Clinical Benefit Rate (No p-value) in 
one table.
2.0040
All 
Treated
RE1a
Summary of Investigator-Assessed Best Response (With 
Confirmation) for Subjects Refractory to Both 
Immunomodulators and Proteasome Inhibitors (IMWG 2011) 
(Part 1)
Report for population subgroup: 
Part 1. Summarize by dose level; 
Do not include Total.
Best Response: Stringent Complete 
Response (sCR), Complete 
response (CR), Very Good Partial 
Response (VGPR), Partial 
Response (PR), Minimal Response 
(MR), Stable Disease (SD), 
Progressive Disease (PD), Not 
Evaluable (NE).
Overall Response Rate: 
(sCR+CR+VGPR+PR).
Clinical Benefit Rate: 
(sCR+CR+VGPR+PR+MR).
Include: Overall Response Rate and 
Clinical Benefit Rate (No p-value) in 
one table.
SAC [A]
2.0041
All 
RE1a
Summary of Investigator-Assessed Best Response (With 
Report for population subgroup: 
SAC [A]


CONFIDENTIAL
BMA117159
155
Efficacy: Tables
No.
Populati
on
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Treated
Confirmation) for Subjects Refractory to Both 
Immunomodulators and Proteasome Inhibitors (IMWG 2011) 
(Part 2 MM)
Part 2 MM. Summarize for 3.4 MM.
Best Response: Stringent Complete 
Response (sCR), Complete 
response (CR), Very Good Partial 
Response (VGPR), Partial 
Response (PR), Minimal Response 
(MR), Stable Disease (SD), 
Progressive Disease (PD), Not 
Evaluable (NE).
Overall Response Rate: 
(sCR+CR+VGPR+PR).
Clinical Benefit Rate: 
(sCR+CR+VGPR+PR+MR).
Include: Overall Response Rate and 
Clinical Benefit Rate (No p-value) in 
one table.
2.0060
All
Evaluabl
e 
Subjects 
MM
RE1a
Summary of Investigator-Assessed Best Response (With 
Confirmation) (IMWG 2011) (All Evaluable Subjects MM)
Report for population subgroup: 
Part 2 MM. Summarize for 3.4 MM.
Best Response: Stringent Complete 
Response (sCR), Complete 
response (CR), Very Good Partial 
Response (VGPR), Partial 
Response (PR), Minimal Response 
(MR), Stable Disease (SD), 
Progressive Disease (PD), Not 
Evaluable (NE).
Overall Response Rate: 
(sCR+CR+VGPR+PR).
IA


CONFIDENTIAL
BMA117159
156
Efficacy: Tables
No.
Populati
on
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Clinical Benefit Rate: 
(sCR+CR+VGPR+PR+MR).
Include: Overall Response Rate and 
Clinical Benefit Rate (No p-value) in 
one table.
2.0342
All 
Treated
RE1a
Summary of Investigator-Assessed Best Response (With 
Confirmation) (RRMCL) (Part 2 NHL)
Report for population subgroup: 
Part 2 NHL. Summarize for 3.4
NHL.
Best Response: Complete response 
(CR), Partial Response (PR). 
Minimal Response (MR), Stable 
Disease (SD), Progressive Disease 
(PD), Not Evaluable (NE). 
Overall Response Rate: (CR+PR).
SAC
Time-to Event Endpoint
2.0081
All 
Treated
TTE1a
Summary of Duration of Response (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize: only for 3.4 
MM. Do not include Hazard Ratio 
and Log-Rank P-Value.Only 
summarize for subjects with a 
confirmed PR or better.
SAC [A]
2.0201
All 
Treated
TTE1
Summary of Duration of Response for Subjects with Prior 
Daratumumab Treatment and Refractory to Both 
Immunomodulators and Proteasome Inhibitors (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize: only for 3.4 
MM. Do not include Hazard Ratio 
and Log-Rank P-Value.
SAC [A]
2.0161
All 
Treated
TTE1
Summary of Duration of Response for Subjects without Prior 
Daratumumab Treatment (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize: only for 3.4 
SAC [A]


CONFIDENTIAL
BMA117159
157
Efficacy: Tables
No.
Populati
on
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
MM. Do not include Hazard Ratio 
and Log-Rank P-Value.
2.0171
All 
Treated
TTE1
Summary of Duration of Response for Subjects Refractory to 
Both Immunomodulators and Proteasome Inhibitors (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize: only for 3.4 
MM. Do not include Hazard Ratio 
and Log-Rank P-Value.
SAC [A]
2.0071
All 
Treated
TTE1
Summary of Progression-Free Survival (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize: only for 3.4 
MM. Do not include Hazard Ratio 
and Log-Rank P-Value.
SAC [A]
2.0261
All 
Treated
TTE1
Summary of Progression-Free Survival for Subjects with Prior 
Daratumumab Treatment and Refractory to Both 
Immunomodulators and Proteasome Inhibitors (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize: only for 3.4 
MM. Do not include Hazard Ratio 
and Log-Rank P-Value.
SAC [A]
2.0131
All 
Treated
TTE1
Summary of Progression-Free Survival for Subjects without Prior 
Daratumumab Treatment (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize: only for 3.4 
MM. Do not include Hazard Ratio 
and Log-Rank P-Value.
SAC [A]
2.0141
All 
Treated
TTE1
Summary of Progression-Free Survival for Subjects Refractory 
to Both Immunomodulators and Proteasome Inhibitors (Part 2 
MM)
Summary of Progression-Free 
Survival for Subjects Refractory to 
Both Immunomodulators and 
Proteasome Inhibitors (Part 2 MM)
SAC [A]
2.0091
All 
Treated
TTE1a
Summary of Time to Response (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize: only for 3.4 
MM. Do not include Hazard Ratio 
and Log-Rank P-Value.
SAC [A]


CONFIDENTIAL
BMA117159
158
Efficacy: Tables
No.
Populati
on
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
2.0101
All 
Treated
TTE1a
Summary of Time to Progression (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize: only for 3.4 
MM. Do not include Hazard Ratio 
and Log-Rank P-Value.
SAC [A]
2.0311
All 
Treated
TTE1a
Summary of Time to Best Response (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize: only for 3.4 
MM. Do not include Hazard Ratio 
and Log-Rank P-Value.
SAC [A]
2.0321
All 
Treated
TTE6a
Summary of Kaplan-Meier Estimates of Overall Survival at 9 
Months (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize: only for 3.4 
MM. Produce if all the patients (who 
were alive at the time of study 
completion) can be re-consented.
SAC
2.0331
All 
Treated
TTE6a
Summary of Kaplan-Meier Estimates of Overall Survival at One 
Year (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize: only for 3.4 
MM. Produced if all the patients 
(who were alive at the time of study 
completion) can be re-consented.
SAC
NOTES: 
A. Indicates which displays will be generated for the reporting effort for multiple myeloma


CONFIDENTIAL
BMA117159
159
16.12.7.
Efficacy Figures
Efficacy: Figures
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
M-Protein and FLC
12.0010
All Treated
RE8b
Percent Change at Maximum Reduction from Baseline in 
M-Protein (or FLC) Measurement (Part 1)
Report for population subgroup: 
Part 1. Include text for best 
confirmed response only. Remove 
subject ID. 
Include reference lines for 25%, 0, -
25%, -50%, -90%, -100%.. Indicate 
lab test types by different symbols. 
Indicate dose groups by different 
colours of the vertical bars.
SAC [A]
12.0011
All Treated
RE8b
Percent Change at Maximum Reduction from Baseline in 
M-Protein (or FLC) Measurement (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Include text for best 
confirmed response only. Remove 
subject ID. 
Include reference lines for 25%, 0, -
25%, -50%, -90%, -100%. Indicate 
lab test types by different shades.
SAC [A]
12.0020
All Treated
EFF_F1
Correlation of Free Soluble BCMA at Pre-Dose (Cycle 1) 
and Maximum Percentage Change from Baseline in Serum 
M-Protein, Urine M-Protein or Serum FLC (Part 1)
Report for population subgroup: 
Part 1. Use best confirmed 
response. Colored by different dose 
groups. Use different symbols to 
indicate Serum M-protein, Urine M-
protein, and Serum FLC. Do not 
include R square and fitted line.
SAC [A]


CONFIDENTIAL
BMA117159
160
Efficacy: Figures
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
12.0021
All Treated
EFF_F1
Correlation of Free Soluble BCMA at Pre-Dose (Cycle 1) 
and Maximum Percentage Change from Baseline in Serum 
M-Protein, Urine M-Protein or Serum FLC (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Use best confirmed 
response. Do not include R square 
and fitted line.
SAC [A]
Time-to-Event Endpoint
12.0041
All Treated
TTE10
Graph of Kaplan Meier Progression-Free Survival Curves 
(Part 2 MM)
Report for population subgroup: 
Part 2 MM. In addition to the 
number of 'At risk', please also 
provide the number of event by 
timepoint for K-M plots.
SAC [A]
12.0161
All Treated
TTE10
Graph of Kaplan Meier Progression-Free Survival Curves 
for Subjects with Prior Daratumumab Treatment and 
Refractory to Both Immunomodulators and Proteasome
Inhibitors (Part 2 MM)
Report for population subgroup: 
Part 2 MM. In addition to the 
number of 'At risk', please also 
provide the number of event by 
timepoint for K-M plots.
SAC [A]
12.0081
All Treated
TTE10
Graph of Kaplan Meier Progression-Free Survival Curves 
for Subjects Refractory to Both Immunomodulators and 
Proteasome Inhibitors (Part 2 MM)
Report for population subgroup: 
Part 2 MM. In addition to the 
number of 'At risk', please also 
provide the number of event by 
timepoint for K-M plots.
SAC [A]
12.0071
All Treated
TTE10
Graph of Kaplan Meier Progression-Free Survival Curves 
for Subjects without Prior Daratumumab Treatment (Part 2 
MM)
Report for population subgroup: 
Part 2 MM. In addition to the 
number of 'At risk', please also 
provide the number of event by 
timepoint for K-M plots.
SAC [A]
12.0051
All Treated
TTE10
Graph of Kaplan Meier Curves of Duration of Response 
Report for population subgroup: 
Part 2 MM.and only for subjects 
SAC [A]


CONFIDENTIAL
BMA117159
161
Efficacy: Figures
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
(Part 2 MM)
with a confirmed PR or better. In 
addition to the number of 'At risk', 
please also provide the number of 
event by timepoint for K-M plots.
12.0171
All Treated
TTE10
Graph of Kaplan Meier Curves of Duration of Response for 
Subjects with Prior Daratumumab Treatment and 
Refractory to Both Immunomodulators and Proteasome
Inhibitors (Part 2 MM)
Report for population subgroup: 
Part 2 MM. In addition to the 
number of 'At risk', please also 
provide the number of event by 
timepoint for K-M plots.
SAC [A]
12.0101
All Treated
TTE10
Graph of Kaplan Meier Curves of Duration of Response for 
Subjects without Prior Daratumumab Treatment (Part 2 
MM)
Report for population subgroup: 
Part 2 MM. In addition to the 
number of 'At risk', please also 
provide the number of event by 
timepoint for K-M plots.
SAC [A]
12.0111
All Treated
TTE10
Graph of Kaplan Meier Curves of Duration of Response for 
Subjects Refractory to Both Immunomodulators and 
Proteasome Inhibitors (Part 2 MM)
Report for population subgroup: 
Part 2 MM. In addition to the 
number of 'At risk', please also 
provide the number of event by 
timepoint for K-M plots.
SAC [A]
Forest Plot
12.0120
All Treated
EFF_F2
Forest Plot - Overall Response Rate (ORR) (Part 2 MM)
SAC [A]
Profile Plot of Responders
12.0150
All Treated
EFF_F3
Profile Plot of Responders (Part 2 MM)
Report for population subgroup: 
Part 2 MM.
SAC [A]
NOTES: 
A. Indicates which displays will be generated for the reporting effort for multiple myeloma


CONFIDENTIAL
BMA117159
162
16.12.8.
Safety Tables
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Adverse Events (AEs)
3.0030
All Treated
OAE01
Summary of All Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0031
All Treated
OAE01
Summary of All Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0032
All Treated
OAE01
Summary of All Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0033
All Treated
OAE01
Summary of All Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0040
All Treated
AE3
Summary of All Adverse Events by Preferred Term (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0041
All Treated
AE3
Summary of All Adverse Events by Preferred Term (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0042
All Treated
AE3
Summary of All Adverse Events by Preferred Term (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0043
All Treated
AE3
Summary of All Adverse Events by Preferred Term (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0910
All Treated
OAE07
Summary of All Adverse Events by Preferred Term and 
Maximum Grade (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0911
All Treated
OAE07
Summary of All Adverse Events by Preferred Term and 
Maximum Grade (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0912
All Treated
OAE07
Summary of All Adverse Events by Preferred Term and 
Maximum Grade (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]


CONFIDENTIAL
BMA117159
163
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0913
All Treated
OAE07
Summary of All Adverse Events by Preferred Term and 
Maximum Grade (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0720
All Treated
OAE1
Summary of All Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade for Subjects with Prior 
Daratumumab Treatment and Refractory to Both 
Immunomodulators and Proteasome Inhibitors (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0721
All Treated
OAE1
Summary of All Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade for Subjects with Prior 
Daratumumab Treatment and Refractory to Both 
Immunomodulators and Proteasome Inhibitors (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0722
All Treated
OAE1
Summary of All Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade for Subjects with Prior 
Daratumumab Treatment and Refractory to Both 
Immunomodulators and Proteasome Inhibitors (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0730
All Treated
OAE1
Summary of All Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade for Subjects without Prior 
Daratumumab Treatment (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0731
All Treated
OAE1
Summary of All Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade for Subjects without Prior 
Daratumumab Treatment (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0732
All Treated
OAE1
Summary of All Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade for Subjects without Prior 
Daratumumab Treatment (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0740
All Treated
OAE1
Summary of All Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade for Subjects Refractory to 
Both Immunomodulators and Proteasome Inhibitors (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]


CONFIDENTIAL
BMA117159
164
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0741
All Treated
OAE1
Summary of All Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade for Subjects Refractory to 
Both Immunomodulators and Proteasome Inhibitors (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0742
All Treated
OAE1
Summary of All Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade for Subjects Refractory to 
Both Immunomodulators and Proteasome Inhibitors (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0750
All Treated
AE3
Summary of All Adverse Events by Preferred Term for Subjects 
with Prior Daratumumab Treatment and Refractory to Both 
Immunomodulators and Proteasome Inhibitors (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0751
All Treated
AE3
Summary of All Adverse Events by Preferred Term for Subjects 
with Prior Daratumumab Treatment and Refractory to Both 
Immunomodulators and Proteasome Inhibitors (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0752
All Treated
AE3
Summary of All Adverse Events by Preferred Term for Subjects 
with Prior Daratumumab Treatment and Refractory to Both 
Immunomodulators and Proteasome Inhibitors (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0760
All Treated
AE3
Summary of All Adverse Events by Preferred Term for Subjects 
without Prior Daratumumab Treatment (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0761
All Treated
AE3
Summary of All Adverse Events by Preferred Term for Subjects 
without Prior Daratumumab Treatment (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0762
All Treated
AE3
Summary of All Adverse Events by Preferred Term for Subjects 
without Prior Daratumumab Treatment (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0770
All Treated
AE3
Summary of All Adverse Events by Preferred Term for Subjects 
Refractory to Both Immunomodulators and Proteasome
Inhibitors (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]


CONFIDENTIAL
BMA117159
165
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0771
All Treated
AE3
Summary of All Adverse Events by Preferred Term for Subjects 
Refractory to Both Immunomodulators and Proteasome
Inhibitors (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0772
All Treated
AE3
Summary of All Adverse Events by Preferred Term for Subjects 
Refractory to Both Immunomodulators and Proteasome
Inhibitors (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0780
All Treated
AE3
Summary of Common (>=5%) Adverse Events by Overall 
Frequency (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0781
All Treated
AE3
Summary of Common (>=5%) Adverse Events by Overall 
Frequency (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0782
All Treated
AE3
Summary of Common (>=5%) Adverse Events by Overall 
Frequency (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0783
All Treated
AE3
Summary of Common (>=5%) Adverse Events by Overall 
Frequency (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0790
All Treated
AE3
Summary of Common (>=5%) Grade 2-4 Adverse Events by 
Overall Frequency (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0791
All Treated
AE3
Summary of Common (>=5%) Grade 2-4 Adverse Events by 
Overall Frequency (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0792
All Treated
AE3
Summary of Common (>=5%) Grade 2-4 Adverse Events by 
Overall Frequency (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0793
All Treated
AE3
Summary of Common (>=5%) Grade 2-4 Adverse Events by 
Overall Frequency (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0060
All Treated
OAE01
Summary of All Drug-Related Adverse Events by System Organ 
Class and Preferred Term and Maximum Grade (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]


CONFIDENTIAL
BMA117159
166
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0061
All Treated
OAE01
Summary of All Drug-Related Adverse Events by System Organ 
Class and Preferred Term and Maximum Grade (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0062
All Treated
OAE01
Summary of All Drug-Related Adverse Events by System Organ 
Class and Preferred Term and Maximum Grade (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0063
All Treated
OAE01
Summary of All Drug-Related Adverse Events by System Organ 
Class and Preferred Term and Maximum Grade (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0690
All Treated
AE15
Summary of Common (>=5%) Non-serious Adverse Events by 
System Organ Class and Preferred Term (Number of 
Participants and Occurrences) (Part 1)
Report for: Part 1, (Summarize by 
ascending dose level, Total). 
SAC [A]
3.0691
All Treated
AE15
Summary of Common (>=5%) Non-serious Adverse Events by 
System Organ Class and Preferred Term (Number of 
Participants and Occurrences) (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). 
SAC [A]
3.0692
All Treated
AE15
Summary of Common (>=5%) Non-serious Adverse Events by 
System Organ Class and Preferred Term (Number of 
Participants and Occurrences) (All Treated MM)
Report for: All Treated MM, 
(Summarize for Total). Include 
baseline values.
SAC [A]
3.0693
All Treated
AE15
Summary of Common (>=5%) Non-serious Adverse Events by 
System Organ Class and Preferred Term (Number of 
Participants and Occurrences) (Part 2 NHL)
Report for: Part 2 NHL, (Summarize 
for Total). Include baseline values.
SAC
3.0710
All Treated
AE3
Summary of Common (>=5%) Drug-Related Grade 2-4 Adverse 
Events by Overall Frequency (Part 1)
Report for: Part 1, (Summarize by 
ascending dose level, Total). 
Include baseline values.
SAC [A]
3.0711
All Treated
AE3
Summary of Common (>=5%) Drug-Related Grade 2-4 Adverse 
Events by Overall Frequency (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Include baseline 
values.
SAC [A]


CONFIDENTIAL
BMA117159
167
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0712
All Treated
AE3
Summary of Common (>=5%) Drug-Related Grade 2-4 Adverse 
Events by Overall Frequency (All Treated MM)
Report for: All Treated MM, 
(Summarize for Total). Include 
baseline values.
SAC [A]
3.0713
All Treated
AE3
Summary of Common (>=5%) Drug-Related Grade 2-4 Adverse 
Events by Overall Frequency (Part 2 NHL)
Report for: Part 2 NHL, (Summarize 
for Total). Include baseline values.
SAC
3.0010
All Treated
AE13
Adverse Event Overview (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0011
All Treated
AE13
Adverse Event Overview (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0012
All Treated
AE13
Adverse Event Overview (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0013
All Treated
AE13
Adverse Event Overview (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0100
All Treated
AE1
Summary of Adverse Events of Maximum Grade 3 or Higher by 
System Organ Class and Preferred Term (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0101
All Treated
AE1
Summary of Adverse Events of Maximum Grade 3 or Higher by 
System Organ Class and Preferred Term (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0102
All Treated
AE1
Summary of Adverse Events of Maximum Grade 3 or Higher by 
System Organ Class and Preferred Term (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0103
All Treated
AE1
Summary of Adverse Events of Maximum Grade 3 or Higher by 
System Organ Class and Preferred Term (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0170
DLT
Evaluable
DL1
Summary of Dose-Limiting Toxicities during the Determinative 
Period (Part 1) (Day 1-21) 
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
Section 3.3.3 of the protocol: An 
event will be
SAC [A]


CONFIDENTIAL
BMA117159
168
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
considered a DLT if its relationship 
to the investigational agent cannot 
be ruled out occurs within the DLT 
reporting period (first 21 days of 
treatment for schedule 1, and
first 28 days for schedule 2)
Serious and Other Significant Adverse Events
3.0700
All Treated
AE16
Summary of Serious Adverse Events by System Organ Class 
and Preferred Term (Number of Participants and Occurrences) 
(Part 1)
Report for: Part 1, (Summarize by 
ascending dose level, Total). 
Include baseline values.
SAC [A]
3.0701
All Treated
AE16
Summary of Serious Adverse Events by System Organ Class 
and Preferred Term (Number of Participants and Occurrences) 
(Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Include baseline 
values.
SAC [A]
3.0702
All Treated
AE16
Summary of Serious Adverse Events by System Organ Class 
and Preferred Term (Number of Participants and Occurrences) 
(All Treated MM)
Report for: All Treated MM, 
(Summarize for Total). Include 
baseline values.
SAC [A]
3.0703
All Treated
AE16
Summary of Serious Adverse Events by System Organ Class 
and Preferred Term (Number of Participants and Occurrences) 
(Part 2 NHL)
Report for: Part 2 NHL, (Summarize 
for Total). Include baseline values.
SAC
3.0080
All Treated
AE1
Summary of Drug-Related Serious Adverse Events by System 
Organ Class and Preferred Term (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0081
All Treated
AE1
Summary of Drug-Related Serious Adverse Events by System 
Organ Class and Preferred Term (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0082
All Treated
AE1
Summary of Drug-Related Serious Adverse Events by System 
Organ Class and Preferred Term (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]


CONFIDENTIAL
BMA117159
169
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0083
All Treated
AE1
Summary of Drug-Related Serious Adverse Events by System 
Organ Class and Preferred Term (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0800
All Treated
AE1
Summary of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment or Withdrawal from Study by 
System Organ Class and Preferred Term (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0801
All Treated
AE1
Summary of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment or Withdrawal from Study by 
System Organ Class and Preferred Term (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0802
All Treated
AE1
Summary of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment or Withdrawal from Study by 
System Organ Class and Preferred Term (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0803
All Treated
AE1
Summary of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment or Withdrawal from Study by 
System Organ Class and Preferred Term (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0120
All Treated
AE1
Summary of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment by System Organ Class and 
Preferred Term (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0121
All Treated
AE1
Summary of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment by System Organ Class and 
Preferred Term (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0122
All Treated
AE1
Summary of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment by System Organ Class and 
Preferred Term (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0123
All Treated
AE1
Summary of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment by System Organ Class and 
Preferred Term (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC


CONFIDENTIAL
BMA117159
170
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0130
All Treated
AE1
Summary of Adverse Events Leading to Dose Reduction by 
System Organ Class and Preferred Term (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0131
All Treated
AE1
Summary of Adverse Events Leading to Dose Reduction by 
System Organ Class and Preferred Term (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0132
All Treated
AE1
Summary of Adverse Events Leading to Dose Reduction by 
System Organ Class and Preferred Term (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0133
All Treated
AE1
Summary of Adverse Events Leading to Dose Reduction by 
System Organ Class and Preferred Term (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0140
All Treated
AE1
Summary of Adverse Events Leading to Dose Interruptions or 
Delays by System Organ Class and Preferred Term (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0141
All Treated
AE1
Summary of Adverse Events Leading to Dose Interruptions or 
Delays by System Organ Class and Preferred Term (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0142
All Treated
AE1
Summary of Adverse Events Leading to Dose Interruptions or 
Delays by System Organ Class and Preferred Term (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0143
All Treated
AE1
Summary of Adverse Events Leading to Dose Interruptions or 
Delays by System Organ Class and Preferred Term (Part 2 
NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0630
All Treated
AE1
Summary of Adverse Events Leading to Dose Reductions, 
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by System Organ Class (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0631
All Treated
AE1
Summary of Adverse Events Leading to Dose Reductions, 
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by System Organ Class (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0632
All Treated
AE1
Summary of Adverse Events Leading to Dose Reductions, 
Report for: All Treated MM, 
SAC [A]


CONFIDENTIAL
BMA117159
171
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by System Organ Class (All Treated MM)
(Summarize: Total).
3.0633
All Treated
AE1
Summary of Adverse Events Leading to Dose Reductions, 
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by System Organ Class (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0640
All Treated
AE1
Summary of Adverse Events Leading to Dose Reductions, 
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by HLGT (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0641
All Treated
AE1
Summary of Adverse Events Leading to Dose Reductions, 
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by HLGT (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0642
All Treated
AE1
Summary of Adverse Events Leading to Dose Reductions, 
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by HLGT (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0643
All Treated
AE1
Summary of Adverse Events Leading to Dose Reductions, 
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by HLGT (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0650
All Treated
AE1
Summary of Adverse Events Leading to Dose Reductions, 
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by HLT (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0651
All Treated
AE1
Summary of Adverse Events Leading to Dose Reductions, 
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by HLT (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0652
All Treated
AE1
Summary of Adverse Events Leading to Dose Reductions, 
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by HLT (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]


CONFIDENTIAL
BMA117159
172
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0653
All Treated
AE1
Summary of Adverse Events Leading to Dose Reductions, 
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by HLT (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0660
All Treated
AE3
Summary of Adverse Events Leading to Dose Reductions, 
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by Preferred Term (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0661
All Treated
AE3
Summary of Adverse Events Leading to Dose Reductions, 
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by Preferred Term (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0662
All Treated
AE3
Summary of Adverse Events Leading to Dose Reductions, 
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by Preferred Term (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0663
All Treated
AE3
Summary of Adverse Events Leading to Dose Reductions, 
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by Preferred Term (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
Adverse Events of Interest
3.0430
All Treated
OAE07
Summary of Corneal Events by Preferred Term and Maximum 
Grade (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0431
All Treated
OAE07
Summary of Corneal Events by Preferred Term and Maximum 
Grade (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM) 
SAC [A]
3.0432
All Treated
OAE07
Summary of Corneal Events by Preferred Term and Maximum 
Grade (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total
SAC [A]
3.0433
All Treated
OAE07
Summary of Corneal Events by Preferred Term and Maximum 
Grade (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) 
SAC
3.0520
All Treated
ESI1
Summary of Characteristics of Corneal Events (Part 1)
Report for: Part 1, (Summarize: by 
SAC [A]


CONFIDENTIAL
BMA117159
173
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
ascending dose level, Total).
Summary based on both all 
subjects and subjects with events.
3.0521
All Treated
ESI1
Summary of Characteristics of Corneal Events (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Summary based 
on both all subjects and subjects 
with events.
SAC [A]
3.0522
All Treated
ESI1
Summary of Characteristics of Corneal Events (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Summary 
based on both all subjects and 
subjects with events.
SAC [A]
3.0523
All Treated
ESI1
Summary of Characteristics of Corneal Events (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
Summary based on both all 
subjects and subjects with events.
SAC
3.0180
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Corneal Events (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). Time 
of onset: 1-21, 22-42, 43-63, >63. 
Duration till resolution: 1-21, 22-42, 
>42.
SAC [A]
3.0181
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Corneal Events (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM) Time of onset: 1-
21, 22-42, 43-63, >63. Duration till 
resolution: 1-21, 22-42, >42.
SAC [A]
3.0182
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of
Corneal Events (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Time of onset: 
1-21, 22-42, 43-63, >63. Duration till 
SAC [A]


CONFIDENTIAL
BMA117159
174
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
resolution: 1-21, 22-42, >42.
3.0183
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Corneal Events (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) Time 
of onset: 1-21, 22-42, 43-63, >63. 
Duration till resolution: 1-21, 22-42, 
>42.
SAC
3.0150
All Treated
AE3
Summary of Corneal Events Leading to Dose Reduction by 
Preferred Term (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0151
All Treated
AE3
Summary of Corneal Events Leading to Dose Reduction by 
Preferred Term (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0152
All Treated
AE3
Summary of Corneal Events Leading to Dose Reduction by 
Preferred Term (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0153
All Treated
AE3
Summary of Corneal Events Leading to Dose Reduction by 
Preferred Term (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0160
All Treated
AE3
Summary of Corneal Events Leading to Dose Interruptions or 
Delays by Preferred Term (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0161
All Treated
AE3
Summary of Corneal Events Leading to Dose Interruptions or 
Delays by Preferred Term (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0162
All Treated
AE3
Summary of Corneal Events Leading to Dose Interruptions or 
Delays by Preferred Term (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0163
All Treated
AE3
Summary of Corneal Events Leading to Dose Interruptions or 
Delays by Preferred Term (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0560
All Treated
OAE07
Summary of Thrombocytopenia by Preferred Term and 
Maximum Grade (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0561
All Treated
OAE07
Summary of Thrombocytopenia by Preferred Term and 
Report for: Part 2 MM, (Summarize: 
SAC [A]


CONFIDENTIAL
BMA117159
175
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Maximum Grade (Part 2 MM)
only for 3.4 MM)
3.0562
All Treated
OAE07
Summary of Thrombocytopenia by Preferred Term and 
Maximum Grade (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0563
All Treated
OAE07
Summary of Thrombocytopenia by Preferred Term and 
Maximum Grade (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0530
All Treated
ESI1
Summary of Characteristics of Thrombocytopenia (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
Summary based on both all 
subjects and subjects with events.
SAC [A]
3.0531
All Treated
ESI1
Summary of Characteristics of Thrombocytopenia (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Summary based 
on both all subjects and subjects 
with events.
SAC [A]
3.0532
All Treated
ESI1
Summary of Characteristics of Thrombocytopenia (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total). Summary 
based on both all subjects and 
subjects with events.
SAC [A]
3.0533
All Treated
ESI1
Summary of Characteristics of Thrombocytopenia (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL). 
Summary based on both all 
subjects and subjects with events.
SAC
3.0190
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Thrombocytopenia (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). Time 
of onset: 1-21, 22-42, 43-63, >63. 
Duration till resolution: 1-21, 22-42, 
>42. Thrombocytopenia should 
SAC [A]


CONFIDENTIAL
BMA117159
176
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
include both 'thrombocytopenia' and 
'platelet count decreased'
3.0191
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Thrombocytopenia (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM) Time of onset: 1-
21, 22-42, 43-63, >63. Duration till 
resolution: 1-21, 22-42, >42. 
Thrombocytopenia should include 
both 'thrombocytopenia' and 
'platelet count decreased'
SAC [A]
3.0192
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Thrombocytopenia (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Time of onset: 
1-21, 22-42, 43-63, >63. Duration till 
resolution: 1-21, 22-42, >42. 
Thrombocytopenia should include 
both 'thrombocytopenia' and 
'platelet count decreased'
SAC [A]
3.0193
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Thrombocytopenia (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) Time 
of onset: 1-21, 22-42, 43-63, >63. 
Duration till resolution: 1-21, 22-42, 
>42. Thrombocytopenia should 
include both 'thrombocytopenia' and 
'platelet count decreased'
SAC
3.0580
All Treated
OAE07
Summary of Neutropenia by Preferred Term and Maximum 
Grade (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0581
All Treated
OAE07
Summary of Neutropenia by Preferred Term and Maximum 
Grade (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]


CONFIDENTIAL
BMA117159
177
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0582
All Treated
OAE07
Summary of Neutropenia by Preferred Term and Maximum 
Grade (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0583
All Treated
OAE07
Summary of Neutropenia by Preferred Term and Maximum 
Grade (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0590
All Treated
ESI1
Summary of Characteristics of Neutropenia (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
Summary based on both all 
subjects and subjects with events.
SAC [A]
3.0591
All Treated
ESI1
Summary of Characteristics of Neutropenia (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Summary based 
on both all subjects and subjects 
with events.
SAC [A]
3.0592
All Treated
ESI1
Summary of Characteristics of Neutropenia (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Summary 
based on both all subjects and 
subjects with events.
SAC [A]
3.0593
All Treated
ESI1
Summary of Characteristics of Neutropenia (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
Summary based on both all 
subjects and subjects with events.
SAC
3.0860
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Neutropenia (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). Time 
of onset: 1-21, 22-42, 43-63, >63. 
Duration till resolution: 1-21, 22-42, 
>42.
SAC [A]
3.0861
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Report for: Part 2 MM, (Summarize: 
SAC [A]


CONFIDENTIAL
BMA117159
178
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Neutropenia (Part 2 MM)
only for 3.4 MM) Time of onset: 1-
21, 22-42, 43-63, >63. Duration till 
resolution: 1-21, 22-42, >42.
3.0862
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Neutropenia (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Time of onset: 
1-21, 22-42, 43-63, >63. Duration till 
resolution: 1-21, 22-42, >42.
SAC [A]
3.0863
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Neutropenia (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) Time 
of onset: 1-21, 22-42, 43-63, >63. 
Duration till resolution: 1-21, 22-42, 
>42.
SAC
3.0550
All Treated
OAE07
Summary of Hematologic Toxicity by Preferred Term and 
Maximum Grade (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0551
All Treated
OAE07
Summary of Hematologic Toxicity by Preferred Term and 
Maximum Grade (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0552
All Treated
OAE07
Summary of Hematologic Toxicity by Preferred Term and 
Maximum Grade (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0553
All Treated
OAE07
Summary of Hematologic Toxicity by Preferred Term and 
Maximum Grade (Part 2 NHL)
Report for: All Treated MM, 
(Summarize: Total).
SAC
3.0540
All Treated
ESI1
Summary of Characteristics of Hematologic Toxicity (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
Summary based on both all 
subjects and subjects with events.
SAC [A]
3.0541
All Treated
ESI1
Summary of Characteristics of Hematologic Toxicity (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Summary based 
SAC [A]


CONFIDENTIAL
BMA117159
179
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
on both all subjects and subjects 
with events.
3.0542
All Treated
ESI1
Summary of Characteristics of Hematologic Toxicity (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total). Summary 
based on both all subjects and 
subjects with events.
SAC [A]
3.0543
All Treated
ESI1
Summary of Characteristics of Hematologic Toxicity (Part 2 
NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
Summary based on both all 
subjects and subjects with events.
SAC
3.0870
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Hematologic Toxicity (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). Time 
of onset: 1-21, 22-42, 43-63, >63. 
Duration till resolution: 1-21, 22-42, 
>42.
SAC [A]
3.0871
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Hematologic Toxicity (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM) Time of onset: 1-
21, 22-42, 43-63, >63. Duration till 
resolution: 1-21, 22-42, >42.
SAC [A]
3.0872
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Hematologic Toxicity (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Time of onset: 
1-21, 22-42, 43-63, >63. Duration till 
resolution: 1-21, 22-42, >42.
SAC [A]
3.0873
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Hematologic Toxicity (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) Time 
of onset: 1-21, 22-42, 43-63, >63. 
Duration till resolution: 1-21, 22-42, 
SAC


CONFIDENTIAL
BMA117159
180
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
>42.
3.0110
All Treated
OAE07
Summary of Infusion-Related Reactions by Preferred Term and 
Maximum Grade (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0111
All Treated
OAE07
Summary of Infusion-Related Reactions by Preferred Term and 
Maximum Grade (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0112
All Treated
OAE07
Summary of Infusion-Related Reactions by Preferred Term and 
Maximum Grade (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0113
All Treated
OAE07
Summary of Infusion-Related Reactions by Preferred Term and 
Maximum Grade (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0600
All Treated
ESI1
Summary of Characteristics of Infusion-Related Reactions (Part 
1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
Summary based on both all 
subjects and subjects with events.
SAC [A]
3.0601
All Treated
ESI1
Summary of Characteristics of Infusion-Related Reactions (Part 
2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Summary based 
on both all subjects and subjects 
with events.
SAC [A]
3.0602
All Treated
ESI1
Summary of Characteristics of Infusion-Related Reactions (All 
Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Summary 
based on both all subjects and 
subjects with events.
SAC [A]
3.0603
All Treated
ESI1
Summary of Characteristics of Infusion-Related Reactions (Part 
2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL). 
Summary based on both all 
subjects and subjects with events.
SAC
3.0880
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Report for: Part 1, (Summarize: by 
SAC [A]


CONFIDENTIAL
BMA117159
181
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Infusion-Related Reactions (Part 1)
ascending dose level, Total). Time 
of onset: 1-21, 22-42, 43-63, >63. 
Duration till resolution: 1-21, 22-42, 
>42.
3.0881
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Infusion-Related Reactions (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM) Time of onset: 1-
21, 22-42, 43-63, >63. Duration till 
resolution: 1-21, 22-42, >42.
SAC [A]
3.0882
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Infusion-Related Reactions (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Time of onset: 
1-21, 22-42, 43-63, >63. Duration till 
resolution: 1-21, 22-42, >42.
SAC [A]
3.0883
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Infusion-Related Reactions (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) Time 
of onset: 1-21, 22-42, 43-63, >63. 
Duration till resolution: 1-21, 22-42, 
>42.
SAC
Laboratory: Chemistry 
3.0270
All Treated
LB1
Summary of Chemistry Changes from Baseline (Part 1)
Report for: Part 1, (Summarize by 
ascending dose level, Total). 
Include baseline values.
SAC [A]
3.0271
All Treated
LB1
Summary of Chemistry Changes from Baseline (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Include baseline 
values.
SAC [A]
3.0272
All Treated
LB1
Summary of Chemistry Changes from Baseline (All Treated MM)
Report for: All Treated MM, 
(Summarize for Total). Include 
SAC [A]


CONFIDENTIAL
BMA117159
182
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
baseline values.
3.0273
All Treated
LB1
Summary of Chemistry Changes from Baseline (Part 2 NHL)
Report for: Part 2 NHL, (Summarize 
for Total). Include baseline values.
SAC
3.0280
All Treated
OLB11B
Summary of Chemistry Changes from Baseline with Respect to 
the Normal Range (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
Include only 'worst-case post-
baseline'
SAC [A]
3.0281
All Treated
OLB11B
Summary of Chemistry Changes from Baseline with Respect to 
the Normal Range (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM) Include only 'worst-
case post-baseline'
SAC [A]
3.0282
All Treated
OLB11B
Summary of Chemistry Changes from Baseline with Respect to 
the Normal Range (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Include only 
'worst-case post-baseline'
SAC [A]
3.0283
All Treated
OLB11B
Summary of Chemistry Changes from Baseline with Respect to 
the Normal Range (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) 
Include only 'worst-case post-
baseline'
SAC
3.0290
All Treated
OLB9B
Summary of Chemistry Grade Changes from Baseline Grade 
(Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
Produce only for lab tests that are 
graded. For laboratory tests that are 
graded for both low and high 
values, summaries will be done 
separately and labeled by direction. 
Include only 'worst-case post-
baseline'
SAC [A]


CONFIDENTIAL
BMA117159
183
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0291
All Treated
OLB9B
Summary of Chemistry Grade Changes from Baseline Grade 
(Part 2 MM)
Report for: Part 2 MM, (Summarize: 
by starting dose level and tumor 
type, Total). Produce only for lab 
tests that are graded. For laboratory 
tests that are graded for both low 
and high values, summaries will be 
done separately and labeled by 
direction. Include only 'worst-case 
post-baseline'
SAC [A]
3.0292
All Treated
OLB9B
Summary of Chemistry Grade Changes from Baseline Grade 
(All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Produce only 
for lab tests that are graded. For 
laboratory tests that are graded for 
both low and high values, 
summaries will be done separately 
and labeled by direction. Include 
only 'worst-case post-baseline'
SAC [A]
3.0293
All Treated
OLB9B
Summary of Chemistry Grade Changes from Baseline Grade 
(Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: Total). Produce only 
for lab tests that are graded. For 
laboratory tests that are graded for 
both low and high values, 
summaries will be done separately 
and labeled by direction. Include 
only 'worst-case post-baseline'
SAC
3.0450
All Treated
OLB11B
Summary of LDH Laboratory Results (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
Include only 'worst-case post-
SAC [A]


CONFIDENTIAL
BMA117159
184
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
baseline'. The categories for 
summary are: <1xULN, >=1xULN 
and < 2xULN, >=2xULN and < 
5xULN, >=5xULN and < 10xULN, 
>=10xULN.
3.0451
All Treated
OLB11B
Summary of LDH Laboratory Results (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM) Include only 'worst-
case post-baseline. The categories 
for summary are: <1xULN, 
>=1xULN and < 2xULN, >=2xULN 
and < 5xULN, >=5xULN and < 
10xULN, >=10xULN.
SAC [A]
3.0452
All Treated
OLB11B
Summary of LDH Laboratory Results (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Include only 
'worst-case post-baseline. The 
categories for summary are: 
<1xULN, >=1xULN and < 2xULN, 
>=2xULN and < 5xULN, >=5xULN 
and < 10xULN, >=10xULN.
SAC [A]
3.0453
All Treated
OLB11B
Summary of LDH Laboratory Results (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) 
Include only 'worst-case post-
baseline. The categories for 
summary are: <1xULN, >=1xULN 
and < 2xULN, >=2xULN and < 
5xULN, >=5xULN and < 10xULN, 
>=10xULN.
SAC


CONFIDENTIAL
BMA117159
185
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0470
All Treated
OLB11B
Summary of Creatine Kinase Laboratory Results (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
Include only 'worst-case post-
baseline'. The categories for 
summary are: <1xULN, >=1xULN 
and < 2xULN, >=2xULN and < 
5xULN, >=5xULN and < 10xULN, 
>=10xULN.
SAC [A]
3.0471
All Treated
OLB11B
Summary of Creatine Kinase Laboratory Results (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM) Include only 'worst-
case post-baseline. The categories 
for summary are: <1xULN, 
>=1xULN and < 2xULN, >=2xULN 
and < 5xULN, >=5xULN and < 
10xULN, >=10xULN.
SAC [A]
3.0472
All Treated
OLB11B
Summary of Creatine Kinase Laboratory Results (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total). Include only 
'worst-case post-baseline. The 
categories for summary are: 
<1xULN, >=1xULN and < 2xULN, 
>=2xULN and < 5xULN, >=5xULN 
and < 10xULN, >=10xULN.
SAC [A]
3.0473
All Treated
OLB11B
Summary of Creatine Kinase Laboratory Results (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) 
Include only 'worst-case post-
baseline. The categories for 
summary are: <1xULN, >=1xULN 
and < 2xULN, >=2xULN and < 
SAC


CONFIDENTIAL
BMA117159
186
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
5xULN, >=5xULN and < 10xULN, 
>=10xULN.
Laboratory: Hematology
3.0300
All Treated
LB1
Summary of Hematology Changes from Baseline (Part 1)
Report for: Part 1, (Summarize by 
ascending dose level, Total). 
Include baseline values.
SAC [A]
3.0301
All Treated
LB1
Summary of Hematology Changes from Baseline (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Include baseline 
values.
SAC [A]
3.0302
All Treated
LB1
Summary of Hematology Changes from Baseline (All Treated 
MM)
Report for: All Treated MM, 
(Summarize for Total). Include 
baseline values.
SAC [A]
3.0303
All Treated
LB1
Summary of Hematology Changes from Baseline (Part 2 NHL)
Report for: Part 2 NHL, (Summarize
for Total). Include baseline values.
SAC
3.0310
All Treated
OLB11B
Summary of Hematology Changes from Baseline with Respect 
to the Normal Range (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
Include only 'worst-case post-
baseline'
SAC [A]
3.0311
All Treated
OLB11B
Summary of Hematology Changes from Baseline with Respect 
to the Normal Range (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM) Include only 'worst-
case post-baseline'
SAC [A]
3.0312
All Treated
OLB11B
Summary of Hematology Changes from Baseline with Respect 
to the Normal Range (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Include only 
'worst-case post-baseline'
SAC [A]
3.0313
All Treated
OLB11B
Summary of Hematology Changes from Baseline with Respect 
to the Normal Range (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) 
SAC


CONFIDENTIAL
BMA117159
187
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Include only 'worst-case post-
baseline'
3.0320
All Treated
OLB9B
Summary of Hematology Grade Changes from Baseline Grade 
(Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
Produce only for lab tests that are 
graded. For laboratory tests that are 
graded for both low and high 
values, summaries will be done 
separately and labeled by direction. 
Include only 'worst-case post-
baseline'
SAC [A]
3.0321
All Treated
OLB9B
Summary of Hematology Grade Changes from Baseline Grade 
(Part 2 MM)
Report for: Part 2 MM, (Summarize: 
by starting dose level and tumor 
type, Total). Produce only for lab 
tests that are graded. For laboratory 
tests that are graded for both low 
and high values, summaries will be 
done separately and labeled by 
direction. Include only 'worst-case 
post-baseline'
SAC [A]
3.0322
All Treated
OLB9B
Summary of Hematology Grade Changes from Baseline Grade 
(All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Produce only 
for lab tests that are graded. For 
laboratory tests that are graded for 
both low and high values, 
summaries will be done separately 
and labeled by direction. Include 
only 'worst-case post-baseline'
SAC [A]


CONFIDENTIAL
BMA117159
188
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0323
All Treated
OLB9B
Summary of Hematology Grade Changes from Baseline Grade 
(Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: Total). Produce only 
for lab tests that are graded. For 
laboratory tests that are graded for 
both low and high values, 
summaries will be done separately 
and labeled by direction. Include 
only 'worst-case post-baseline'
SAC
Laboratory: Urinalysis
3.0360
All Treated
LB1
Summary of Urine Concentration Changes from Baseline (Part 
1)
Report for: Part 1, (Summarize by 
ascending dose level, Total). 
Include baseline values.
SAC [A]
3.0361
All Treated
LB1
Summary of Urine Concentration Changes from Baseline (Part 2 
MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Include baseline 
values.
SAC [A]
3.0362
All Treated
LB1
Summary of Urine Concentration Changes from Baseline (All 
Treated MM)
Report for: All Treated MM, 
(Summarize for Total). Include 
baseline values.
SAC [A]
3.0363
All Treated
LB1
Summary of Urine Concentration Changes from Baseline (Part 2 
NHL)
Report for: Part 2 NHL, (Summarize 
for Total). Include baseline values.
SAC
3.0680
All Treated
UR1
Summary of Worst Case Urinalysis Results (Discrete or 
Character Values) Post-Baseline Relative to Baseline (Part 1)
Report for: Part 1, (Summarize by 
ascending dose level, Total). 
Include baseline values.
SAC [A]
3.0681
All Treated
UR1
Summary of Worst Case Urinalysis Results (Discrete or 
Character Values) Post-Baseline Relative to Baseline (Part 2 
MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Include baseline 
values.
SAC [A]


CONFIDENTIAL
BMA117159
189
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0682
All Treated
UR1
Summary of Worst Case Urinalysis Results (Discrete or 
Character Values) Post-Baseline Relative to Baseline (All 
Treated MM)
Report for: All Treated MM, 
(Summarize for Total). Include 
baseline values.
SAC [A]
3.0683
All Treated
UR1
Summary of Worst Case Urinalysis Results (Discrete or 
Character Values) Post-Baseline Relative to Baseline (Part 2 
NHL)
Report for: Part 2 NHL, (Summarize 
for Total). Include baseline values.
SAC
Laboratory: Hepatobiliary (Liver)
3.0200
All Treated
LIVER1
Summary of Liver Monitoring/Stopping Event Reporting (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0201
All Treated
LIVER1
Summary of Liver Monitoring/Stopping Event Reporting (Part 2 
MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0202
All Treated
LIVER1
Summary of Liver Monitoring/Stopping Event Reporting (All 
Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0203
All Treated
LIVER1
Summary of Liver Monitoring/Stopping Event Reporting (Part 2 
NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0210
All Treated
LIVER10
Summary of Hepatobiliary Laboratory Abnormalities (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0211
All Treated
LIVER10
Summary of Hepatobiliary Laboratory Abnormalities (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0212
All Treated
LIVER10
Summary of Hepatobiliary Laboratory Abnormalities (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0213
All Treated
LIVER10
Summary of Hepatobiliary Laboratory Abnormalities (Part 2 
NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC


CONFIDENTIAL
BMA117159
190
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Laboratory: Coagulation
3.0330
All Treated
LB1
Summary of Coagulation Changes from Baseline (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0331
All Treated
LB1
Summary of Coagulation Changes from Baseline (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0332
All Treated
LB1
Summary of Coagulation Changes from Baseline (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0333
All Treated
LB1
Summary of Coagulation Changes from Baseline (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0340
All Treated
OLB11B
Summary of Coagulation Changes from Baseline with Respect 
to the Normal Range (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
Include only 'worst-case post-
baseline'
SAC [A]
3.0341
All Treated
OLB11B
Summary of Coagulation Changes from Baseline with Respect 
to the Normal Range (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Include only 
'worst-case post-baseline'
SAC [A]
3.0342
All Treated
OLB11B
Summary of Coagulation Changes from Baseline with Respect 
to the Normal Range (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Include only 
'worst-case post-baseline'
SAC [A]
3.0343
All Treated
OLB11B
Summary of Coagulation Changes from Baseline with Respect 
to the Normal Range (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL). 
Include only 'worst-case post-
baseline'
SAC
3.0350
All Treated
OLB9B
Summary of Coagulation Grade Changes from Baseline Grade 
(Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
Produce only for lab tests that are 
SAC [A]


CONFIDENTIAL
BMA117159
191
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
graded. For laboratory tests that are 
graded for both low and high 
values, summaries will be done 
separately and labeled by direction.
3.0351
All Treated
OLB9B
Summary of Coagulation Grade Changes from Baseline Grade 
(Part 2 MM)
Report for: Part 2 MM, (Summarize: 
by starting dose level and tumor 
type, Total). Produce only for lab 
tests that are graded. For laboratory 
tests that are graded for both low 
and high values, summaries will be 
done separately and labeled by 
direction.
SAC [A]
3.0352
All Treated
OLB9B
Summary of Coagulation Grade Changes from Baseline Grade 
(All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Produce only 
for lab tests that are graded. For 
laboratory tests that are graded for 
both low and high values, 
summaries will be done separately 
and labeled by direction.
SAC [A]
3.0353
All Treated
OLB9B
Summary of Coagulation Grade Changes from Baseline Grade 
(Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: Total). Produce only 
for lab tests that are graded. For 
laboratory tests that are graded for 
both low and high values, 
summaries will be done separately 
and labeled by direction.
SAC


CONFIDENTIAL
BMA117159
192
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
ECG
3.0370
All Treated
EG1
Summary of ECG Findings (Part 1)
Report for: Part 1, (Summarize by 
ascending dose level, Total). 
Include baseline values.
SAC [A]
3.0371
All Treated
EG1
Summary of ECG Findings (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Include baseline 
values.
SAC [A]
3.0372
All Treated
EG1
Summary of ECG Findings (All Treated MM)
Report for: All Treated MM, 
(Summarize for Total). Include 
baseline values.
SAC [A]
3.0373
All Treated
EG1
Summary of ECG Findings (Part 2 NHL)
Report for: All Treated MM, 
(Summarize for Total). Include 
baseline values.
SAC
3.0390
All Treated
OECG1B
Summary of Worst-case Increases in Fridericia's QTc (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
Include only 'worst-case post-
baseline'
SAC [A]
3.0391
All Treated
OECG1B
Summary of Worst-case Increases in Fridericia's QTc (Part 2 
MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM) Include only 'worst-
case post-baseline'
SAC [A]
3.0392
All Treated
OECG1B
Summary of Worst-case Increases in Fridericia's QTc (All 
Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Include only 
'worst-case post-baseline'
SAC [A]
3.0393
All Treated
OECG1B
Summary of Worst-case Increases in Fridericia's QTc (Part 2 
NHL)
Report for: Part 2 NHL, 
(Summarize: Total). Include only 
'worst-case post-baseline'
SAC


CONFIDENTIAL
BMA117159
193
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0400
All Treated
OECG2B
Summary of Worst-case Amount of Increase from Baseline 
Value in Fridericia's QTc (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
Include only 'worst-case post-
baseline'
SAC [A]
3.0401
All Treated
OECG2B
Summary of Worst-case Amount of Increase from Baseline 
Value in Fridericia's QTc (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM) Include only 'worst-
case post-baseline'
SAC [A]
3.0402
All Treated
OECG2B
Summary of Worst-case Amount of Increase from Baseline 
Value in Fridericia's QTc (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Include only 
'worst-case post-baseline'
SAC [A]
3.0403
All Treated
OECG2B
Summary of Worst-case Amount of Increase from Baseline 
Value in Fridericia's QTc (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: Total). Include only 
'worst-case post-baseline'
SAC
3.0380
All Treated
EG2
Summary of Change from Baseline in ECG Values by Visit (Part 
1)
Report for: Part 1, (Summarize by 
ascending dose level, Total). 
Include baseline values.
SAC [A]
3.0381
All Treated
EG2
Summary of Change from Baseline in ECG Values by Visit (Part 
2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Include baseline 
values.
SAC [A]
3.0382
All Treated
EG2
Summary of Change from Baseline in ECG Values by Visit (All 
Treated MM)
Report for: All Treated MM, 
(Summarize for Total). Include 
baseline values.
SAC [A]
3.0383
All Treated
EG2
Summary of Change from Baseline in ECG Values by Visit (Part 
2 NHL)
Report for: Part 2 NHL, (Summarize 
for Total). Include baseline values.
SAC


CONFIDENTIAL
BMA117159
194
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Vital Signs
3.0220
All Treated
VS1
Summary of Change from Baseline in Vital Signs (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). Add 
Cycle, Visit. Include baseline 
values.
SAC [A]
3.0221
All Treated
VS1
Summary of Change from Baseline in Vital Signs (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM) Add Cycle, Visit. 
Include baseline values.
SAC [A]
3.0222
All Treated
VS1
Summary of Change from Baseline in Vital Signs (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total). Add Cycle, 
Visit. Include baseline values.
SAC [A]
3.0223
All Treated
VS1
Summary of Change from Baseline in Vital Signs (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) Add 
Cycle, Visit. Include baseline 
values.
SAC
3.0230
All Treated
OVT1B
Summary of Changes in Heart Rate from Baseline (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
Include only 'worst-case post-
baseline'
SAC [A]
3.0231
All Treated
OVT1B
Summary of Changes in Heart Rate from Baseline (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM) Include only 'worst-
case post-baseline'
SAC [A]
3.0232
All Treated
OVT1B
Summary of Changes in Heart Rate from Baseline (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total). Include only 
'worst-case post-baseline'
SAC [A]


CONFIDENTIAL
BMA117159
195
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0233
All Treated
OVT1B
Summary of Changes in Heart Rate from Baseline (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) 
Include only 'worst-case post-
baseline'
SAC
3.0240
All Treated
OVT2B
Summary of Increases in Systolic Blood Pressure from Baseline 
(Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0241
All Treated
OVT2B
Summary of Increases in Systolic Blood Pressure from Baseline 
(Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0242
All Treated
OVT2B
Summary of Increases in Systolic Blood Pressure from Baseline 
(All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Include only 
'worst-case post-baseline'
SAC [A]
3.0243
All Treated
OVT2B
Summary of Increases in Systolic Blood Pressure from Baseline 
(Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) 
Include only 'worst-case post-
baseline'
SAC
3.0250
All Treated
OVT2B
Summary of Increases in Diastolic Blood Pressure from Baseline 
(Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
Include only 'worst-case post-
baseline'
SAC [A]
3.0251
All Treated
OVT2B
Summary of Increases in Diastolic Blood Pressure from Baseline 
(Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM) Include only 'worst-
case post-baseline'
SAC [A]
3.0252
All Treated
OVT2B
Summary of Increases in Diastolic Blood Pressure from Baseline 
(All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Include only 
'worst-case post-baseline'
SAC [A]


CONFIDENTIAL
BMA117159
196
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0253
All Treated
OVT2B
Summary of Increases in Diastolic Blood Pressure from Baseline 
(Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) 
Include only 'worst-case post-
baseline'
SAC
3.0260
All Treated
OVT1B
Summary of Changes in Temperature from Baseline (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
Include only 'worst-case post-
baseline'
SAC [A]
3.0261
All Treated
OVT1B
Summary of Changes in Temperature from Baseline (Part 2 
MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM) Include only 'worst-
case post-baseline'
SAC [A]
3.0262
All Treated
OVT1B
Summary of Changes in Temperature from Baseline (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total). Include only 
'worst-case post-baseline'
SAC [A]
3.0263
All Treated
OVT1B
Summary of Changes in Temperature from Baseline (Part 2 
NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) 
Include only 'worst-case post-
baseline'
SAC
ECOG Performance Status
3.0410
All Treated
PS1A
Summary of ECOG Performance Status (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0411
All Treated
PS1A
Summary of ECOG Performance Status (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0412
All Treated
PS1A
Summary of ECOG Performance Status (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]


CONFIDENTIAL
BMA117159
197
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0413
All Treated
PS1A
Summary of ECOG Performance Status (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0420
All Treated
PS3A
Summary of Change in ECOG Performance Status from 
Baseline (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0421
All Treated
PS3A
Summary of Change in ECOG Performance Status from 
Baseline (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0422
All Treated
PS3A
Summary of Change in ECOG Performance Status from 
Baseline (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0423
All Treated
PS3A
Summary of Change in ECOG Performance Status from 
Baseline (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
Left Ventricular Ejection Fraction
3.0480
All Treated
OLVEF1
A
Summary of Left Ventricular Ejection Fraction Change from 
Baseline (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
Footnote: LLN: Normal Range 
Lower Limit.
SAC [A]
3.0481
All Treated
OLVEF1
A
Summary of Left Ventricular Ejection Fraction Change from 
Baseline (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Footnote: LLN: 
Normal Range Lower Limit.
SAC [A]
3.0482
All Treated
OLVEF1
A
Summary of Left Ventricular Ejection Fraction Change from 
Baseline (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Footnote: LLN: 
Normal Range Lower Limit.
SAC [A]
3.0483
All Treated
OLVEF1
A
Summary of Left Ventricular Ejection Fraction Change from 
Baseline (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC


CONFIDENTIAL
BMA117159
198
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Ocular Exams
3.0490
All Treated
SAFE_T
1
Summary of Subjects Experiencing Corneal Clinical Signs (Part 
1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0491
All Treated
SAFE_T
1
Summary of Subjects Experiencing Corneal Clinical Signs (Part 
2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0492
All Treated
SAFE_T
1
Summary of Subjects Experiencing Corneal Clinical Signs (All 
Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0493
All Treated
SAFE_T
1
Summary of Subjects Experiencing Corneal Clinical Signs (Part 
2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0500
All Treated
SAFE_T
2
Summary of Best Corrected Visual Acuity Test (BCVA) Scores 
(logMAR score) (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0501
All Treated
SAFE_T
2
Summary of Best Corrected Visual Acuity Test (BCVA) Scores 
(logMAR score) (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0502
All Treated
SAFE_T
2
Summary of Best Corrected Visual Acuity Test (BCVA) Scores 
(logMAR score) (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0503
All Treated
SAFE_T
2
Summary of Best Corrected Visual Acuity Test (BCVA) Scores 
(logMAR score) (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
Death
3.0570
All Treated
DTH1a
Summary of Deaths (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0571
All Treated
DTH1a
Summary of Deaths (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0572
All Treated
DTH1a
Summary of Deaths (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]


CONFIDENTIAL
BMA117159
199
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0573
All Treated
DTH1a
Summary of Deaths (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
Constitutional B- Symptoms
3.0813
All Treated
OCS1
Summary of Constitutional Symptoms over Time (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
Organ Examination
3.0823
All Treated
OOE1
Summary of Organ Examination over Time (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
Health Outcome
3.0830
All Treated
SAFE_T
3
Summary of Symptom Impact and HRQoL Item Scores (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0831
All Treated
SAFE_T
3
Summary of Symptom Impact and HRQoL Item Scores (Part 2 
MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0832
All Treated
SAFE_T
3
Summary of Symptom Impact and HRQoL Item Scores (All 
Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0833
All Treated
SAFE_T
3
Summary of Symptom Impact and HRQoL Item Scores (Part 2 
NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC


CONFIDENTIAL
BMA117159
200
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Anti-Drug Antibody
3.0840
All Treated
SAFE_T
4
Summary of Human Anti-GSK2857916 Antibodies (ADA) Over 
Time (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0841
All Treated
SAFE_T
4
Summary of Human Anti-GSK2857916 Antibodies (ADA) Over 
Time (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0842
All Treated
SAFE_T
4
Summary of Human Anti-GSK2857916 Antibodies (ADA) Over 
Time (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0843
All Treated
SAFE_T
4
Summary of Human Anti-GSK2857916 Antibodies (ADA) Over 
Time (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0850
All Treated
SAFE_T
5
Summary of Anti-GSK2857916 Antibodies (ADA) (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0851
All Treated
SAFE_T
5
Summary of Anti-GSK2857916 Antibodies (ADA) (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0852
All Treated
SAFE_T
5
Summary of Anti-GSK2857916 Antibodies (ADA) (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0853
All Treated
SAFE_T
5
Summary of Anti-GSK2857916 Antibodies (ADA) (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
NOTES: 
A. Indicates which displays will be generated for the reporting effort for multiple myeloma


CONFIDENTIAL
BMA117159
201
16.12.9.
Safety Figures
Safety: Figures
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Laboratory
13.0130
All Treated
LIVER14
Scatter Plot of Maximum vs. Baseline for ALT (Part 1)
Report for sub-population: Part 1. 
Pool all subjects together.
SAC [A]
13.0131
All Treated
LIVER14
Scatter Plot of Maximum vs. Baseline for ALT (Part 2 MM)
Report for sub-population: Part 2 
MM.
SAC [A]
13.0133
All Treated
LIVER14
Scatter Plot of Maximum vs. Baseline for ALT (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
13.0120
All Treated
LIVER9
Scatter Plot of Maximum Bilirubin versus Maximum ALT -
eDISH (Part 1)
Report for sub-population: Part 1. 
Pool all subjects together.
SAC [A]
13.0121
All Treated
LIVER9
Scatter Plot of Maximum Bilirubin versus Maximum ALT -
eDISH (Part 2 MM)
Report for sub-population: Part 2 
MM.
SAC [A]
13.0122
All Treated
LIVER9
Scatter Plot of Maximum Bilirubin versus Maximum ALT -
eDISH (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
13.0140
All Treated
LIVER9
Scatter Plot of Maximum AST vs Maximum LDH - eDISH Plot 
(Part 1)
Report for sub-population: Part 1. 
Pool all subjects together. Bold 
reference lines are not needed. 
Do not include Hy's Quadrant and 
Temple's Corollary.
SAC [A]
13.0141
All Treated
LIVER9
Scatter Plot of Maximum AST vs Maximum LDH - eDISH Plot 
(Part 2 MM)
Report for sub-population: Part 2 
MM. Do not include Hy's Quadrant 
and Temple's Corollary.
SAC [A]


CONFIDENTIAL
BMA117159
202
Safety: Figures
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
13.0142
All Treated
LIVER9
Scatter Plot of Maximum AST vs Maximum LDH - eDISH Plot 
(Part 2 NHL)
Report for sub-population: Part 2 
NHL. Do not include Hy's 
Quadrant and Temple's Corollary.
SAC
13.0150
All Treated
LIVER9
Scatter Plot of Maximum AST vs Maximum Creatinine Kinase -
eDISH Plot (Part 1)
Report for sub-population: Part 1. 
Pool all subjects together. Bold 
reference lines are not needed. 
Do not include Hy's Quadrant and 
Temple's Corollary.
SAC [A]
13.0151
All Treated
LIVER9
Scatter Plot of Maximum AST vs Maximum Creatinine Kinase -
eDISH Plot (Part 2 MM)
Report for sub-population: Part 2 
MM. Do not include Hy's Quadrant 
and Temple's Corollary.
SAC [A]
13.0152
All Treated
LIVER9
Scatter Plot of Maximum AST vs Maximum Creatinine Kinase -
eDISH Plot (Part 2 NHL)
Report for sub-population: Part 2 
NHL. Do not include Hy's 
Quadrant and Temple's Corollary.
SAC
Adverse Events
13.0160
All Treated
SAFE_F1
Proportions of Subjects with Infusion-related Reactions (Part 1)
Report for sub-population: Part 1. 
Pool all subjects together.
SAC [A]
13.0161
All Treated
SAFE_F1
Proportions of Subjects with Infusion-related Reactions (Part 2 
MM)
Report for sub-population: Part 2 
MM.
SAC [A]
ECG
13.0200
All Treated
OECG4
Fridericia's QTc Shifts from Baseline to Worst-case Post 
Baseline (Part 1)
Report for sub-population: Part 1. 
Pool all subjects together. If 
machine read QTcF is missing, 
use the manual read QTcF and 
add footnote that Machine and 
Manual calculate values are 
SAC [A]


CONFIDENTIAL
BMA117159
203
Safety: Figures
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
collapsed together.
13.0201
All Treated
OECG4
Fridericia's QTc Shifts from Baseline to Worst-case Post 
Baseline (Part 2 MM)
Report for sub-population: Part 2 
MM. If machine read QTcF is 
missing, use the manual read 
QTcF, and add footnote that 
Machine and Manual calculate 
values are collapsed together
SAC [A]
13.0202
All Treated
OECG4
Fridericia's QTc Shifts from Baseline to Worst-case Post 
Baseline (Part 2 NHL)
Report for sub-population: Part 2 
NHL. If machine read QTcF is 
missing, use the manual read 
QTcF, and add footnote that 
Machine and Manual calculate 
values are collapsed together
SAC
Patient Profile Plot
13.0190
All Treated
SAFE_F2
Profile Plot for Patients with No Corneal Event or Only Grade 1 
Corneal Event (Part 2 MM)
Report for sub-population: Part 2 
MM.
SAC [A]
13.0191
All Treated
SAFE_F2
Profile Plot for Patients with Grade 2 or Higher Corneal Events 
(Part 2 MM) 
Report for sub-population: Part 2 
MM.
SAC [A]
NOTES: 
A. Indicates which displays will be generated for the reporting effort for multiple myeloma


CONFIDENTIAL
BMA117159
204
16.12.10. Pharmacokinetic Tables
Pharmacokinetic: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Concentration
4.0010
PK
PK01
Summary of Plasma GSK2857916 (ADC) PK Concentration-
Time Data (Part 1)
By dose level
SAC [A]
4.0011
PK
PK01
Summary of Plasma GSK2857916 (ADC) PK Concentration-
Time Data (Part 2 MM)
SAC [A]
4.0013
PK
PK01
Summary of Plasma GSK2857916 (ADC) PK Concentration-
Time Data (Part 2 NHL)
SAC
4.0020
PK
PK01
Summary of Plasma GSK2857916 (Total Antibody) PK 
Concentration-Time Data (Part 1)
By dose level
SAC [A]
4.0021
PK
PK01
Summary of Plasma GSK2857916 (Total Antibody) PK 
Concentration-Time Data (Part 2 MM)
SAC [A]
4.0023
PK
PK01
Summary of Plasma GSK2857916 (Total Antibody) PK
Concentration-Time Data (Part 2 NHL)
SAC
4.0030
PK
PK01
Summary of Plasma GSK2857916 (Unbound Antibody) PK 
Concentration-Time Data (Part 1)
By dose level
SAC [A]
4.0031
PK
PK01
Summary of Plasma GSK2857916 (Unbound Antibody) PK 
Concentration-Time Data (Part 2 MM)
If data was not collected, present “No 
data to report”
SAC [A]
4.0033
PK
PK01
Summary of Plasma GSK2857916 (Unbound Antibody) PK 
Concentration-Time Data (Part 2 NHL)
If data was not collected, present “No 
data to report”
SAC
4.0040
PK
PK01
Summary of Plasma cys-mcMMAF PK Concentration-Time 
Data (Part 1)
By dose level
SAC [A]


CONFIDENTIAL
BMA117159
205
Pharmacokinetic: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
4.0041
PK
PK01
Summary of Plasma cys-mcMMAF PK Concentration-Time 
Data (Part 2 MM)
SAC [A]
4.0043
PK
PK01
Summary of Plasma cys-mcMMAF PK Concentration-Time 
Data (Part 2 NHL)
SAC
PK Parameter
4.0050
PK
PK06
Summary of Derived GSK2857916 (ADC) PK Parameters 
(Part 1)
By dose level
PK06 with both transformed and 
untransformed values. 
SAC [A]
4.0051
PK
PK06
Summary of Derived GSK2857916 (ADC) PK Parameters 
(Part 2 MM)
PK06 with both transformed and 
untransformed values. 
SAC [A]
4.0053
PK
PK06
Summary of Derived GSK2857916 (ADC) PK Parameters 
(Part 2 NHL)
PK06 with both transformed and 
untransformed values. 
SAC
4.0060
PK
PK06
Summary of Derived GSK2857916 (Total Antibody) PK 
Parameters (Part 1)
By dose level
PK06 with both transformed and 
untransformed values. 
SAC [A]
4.0061
PK
PK06
Summary of Derived GSK2857916 (Total Antibody) PK 
Parameters (Part 2 MM)
PK06 with both transformed and 
untransformed values. 
SAC [A]
4.0063
PK
PK06
Summary of Derived GSK2857916 (Total Antibody) PK 
Parameters (Part 2 NHL)
PK06 with both transformed and 
untransformed values. 
SAC
4.0070
PK
PK06
Summary of Derived GSK2857916 (Unbound Antibody) PK 
Parameters (Part 1)
By dose level
PK06 with both transformed and 
untransformed values. 
SAC [A]
4.0071
PK
PK06
Summary of Derived GSK2857916 (Unbound Antibody) PK 
Parameters (Part 2 MM)
PK06 with both transformed and 
untransformed values. If data was 
not collected, present “No data to 
SAC [A]


CONFIDENTIAL
BMA117159
206
Pharmacokinetic: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
report”
4.0073
PK
PK06
Summary of Derived GSK2857916 (Unbound Antibody) PK 
Parameters (Part 2 NHL)
PK06 with both transformed and 
untransformed values. If data was 
not collected, present “No data to 
report”
SAC
4.0080
PK
PK06
Summary of Derived cys-mcMMAF PK Parameter (Part 1)
By dose level
PK06 with both transformed and 
untransformed values.
SAC [A]
4.0081
PK
PK06
Summary of Derived cys-mcMMAF PK Parameter (Part 2 MM)
PK06 with both transformed and 
untransformed values.
SAC [A]
4.0083
PK
PK06
Summary of Derived cys-mcMMAF PK Parameter (Part 2 
NHL)
PK06 with both transformed and 
untransformed values. 
SAC
4.0090
PK
PK13
Listing of Derived GSK2857916 (ADC) PK Parameters 
(Untransformed) (MM)
SAC [A]
4.0091
PK
PK13
Listing of Derived GSK2857916 (ADC) PK Parameters 
(Untransformed) (NHL)
SAC
4.0100
PK
PK13
Listing of Derived GSK2857916 (Total Antibody) PK 
Parameters (Untransformed) (MM)
SAC [A]
4.0101
PK
PK13
Listing of Derived GSK2857916 (Total Antibody) PK 
Parameters (Untransformed) (NHL)
SAC
4.0110
PK
PK13
Listing of Derived GSK2857916 (Unbound Antibody) PK 
Parameters (Untransformed) (MM)
SAC [A]
4.0111
PK
PK13
Listing of Derived GSK2857916 (Unbound Antibody) PK 
Parameters (Untransformed) (NHL)
SAC
4.0120
PK
PK13
Listing of Derived cys-mcMMAF PK Parameters 
SAC [A]


CONFIDENTIAL
BMA117159
207
Pharmacokinetic: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
(Untransformed) (MM)
4.0121
PK
PK13
Listing of Derived cys-mcMMAF PK Parameters 
(Untransformed) (NHL)
SAC
4.0130
PK
PK03
Summary of cys-mcMMAF Pharmacokinetic Urine Excretin 
Data (Part 1)
SAC [A]
4.0140
PK
PK11
Listing of cys-mcMMAF Urine Excretion Data (Part 1)
replace Amount Excreted and 
Excretion Rate with Ae(0-24) and 
Fe
SAC [A]


CONFIDENTIAL
BMA117159
208
Pharmacokinetic: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Dose Proportionality Analysis
4.0150
PK
PK_T1
Summary of Results of Dose Proportionality Analysis for 
GSK2857916 (ADC), GSK2857916 (Total Antibody), 
GSL2857916 (Unbound Antibody), and cys-mcMMAF PK 
Parameters Using Power Model (Part 1)
Example:
AUC(0-inf), AUC(0-t), AUC(0- τ), 
Cmax, and Ctrough
SAC [A]
Accumulation Ratio
4.0160
PK
PK05
Summary of Results of Accumulation Ratio Assessment for 
GSK2857916 (ADC) (Part 1)
By dose level, include Ro(CEOI) 
and Ro(Ctrough) in one table.
95%CI
SAC [A]
4.0161
PK
PK05
Summary of Results of Accumulation Ratio Assessment for 
GSK2857916 (ADC) (Part 2 MM)
Include Ro(CEOI) and 
Ro(Ctrough) in one table. 95%CI
SAC [A]
4.0163
PK
PK05
Summary of Results of Accumulation Ratio Assessment for 
GSK2857916 (ADC) (Part 2 NHL)
Include Ro(CEOI) and
Ro(Ctrough) in one table. 95%CI
SAC
4.0170
PK
PK05
Summary of Results of Accumulation Ratio Assessment for 
GSK2857916 (Total Antibody) (Part 1)
By dose level, include Ro(CEOI) 
and Ro(Ctrough) in one table. 
95%CI
SAC [A]
4.0171
PK
PK05
Summary of Results of Accumulation Ratio Assessment for 
GSK2857916 (Total Antibody) (Part 2 MM)
Include Ro(CEOI) and 
Ro(Ctrough) in one table. 95%CI
SAC [A]
4.0173
PK
PK05
Summary of Results of Accumulation Ratio Assessment for 
GSK2857916 (Total Antibody) (Part 2 NHL)
Include Ro(CEOI) and 
Ro(Ctrough) in one table. 95%CI
SAC
4.0180
PK
PK05
Summary of Results of Accumulation Ratio Assessment for 
GSK2857916 (Unbound Antibody) (Part 1)
By dose level, include Ro(CEOI) 
and Ro(Ctrough) in one table. 
95%CI
SAC [A]
4.0181
PK
PK05
Summary of Results of Accumulation Ratio Assessment for 
Include Ro(CEOI) and 
SAC [A]
PPD
PPD


CONFIDENTIAL
BMA117159
209
Pharmacokinetic: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
GSK2857916 (Unbound Antibody) (Part 2 MM)
Ro(Ctrough) in one table. 95%CI
4.0183
PK
PK05
Summary of Results of Accumulation Ratio Assessment for 
GSK2857916 (Unbound Antibody) (Part 2 NHL)
Include Ro(CEOI) and 
Ro(Ctrough) in one table. 95%CI
SAC
4.0190
PK
PK05
Summary of Results of Accumulation Ratio Assessment for 
cys-mcMMAF (Part 1)
By dose level, include Ro(CEOI) 
and Ro(Ctrough) in one table. 
95%CI
SAC [A]
4.0191
PK
PK05
Summary of Results of Accumulation Ratio Assessment for 
cys-mcMMAF (Part 2 MM)
Include Ro(CEOI) and 
Ro(Ctrough) in one table. 95%CI
SAC [A]
4.0193
PK
PK05
Summary of Results of Accumulation Ratio Assessment for 
cys-mcMMAF (Part 2 NHL)
Include Ro(CEOI) and 
Ro(Ctrough) in one table. 95%CI
SAC
Analyte Ratio
4.0200
PK
PK05
Summary of Results of Analyte Ratio Assessment for 
GSK2857916 (Total Antibody) (Part 1)
By dose level and cycle, include 
Ra(CEOI) and Ra(Ctrough) in one 
table. 95%CI
SAC [A]
4.0201
PK
PK05
Summary of Results of Analyte Ratio Assessment for 
GSK2857916 (Total Antibody) (Part 2 MM)
Include Ra(CEOI) and Ra(Ctrough) 
in one table. 95%CI
SAC [A]
4.0203
PK
PK05
Summary of Results of Analyte Ratio Assessment for 
GSK2857916 (Total Antibody) (Part 2 NHL)
Include Ra(CEOI) and Ra(Ctrough) 
in one table. 95%CI
SAC
4.0210
PK
PK05
Summary of Results of Analyte Ratio Assessment for 
GSK2857916 (Unbound Antibody) (Part 1)
By dose level and cycle, include 
Ra(CEOI) and Ra(Ctrough) in one 
table. 95%CI
SAC [A]
4.0211
PK
PK05
Summary of Results of Analyte Ratio Assessment for 
GSK2857916 (Unbound Antibody) (Part 2 MM)
Include Ra(CEOI) and Ra(Ctrough) 
in one table. 95%CI
SAC [A]
4.0213
PK
PK05
Summary of Results of Analyte Ratio Assessment for 
GSK2857916 (Unbound Antibody) (Part 2 NHL)
Include Ra(CEOI) and Ra(Ctrough) 
in one table. 95%CI
SAC


CONFIDENTIAL
BMA117159
210
Pharmacokinetic: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
4.0220
PK
PK05
Summary of Results of Analyte Ratio Assessment for cys-
mcMMAF (Part 1)
By dose level and cycle, include 
Ra(CEOI) and Ra(Ctrough) in one 
table. 95%CI
SAC [A]
4.0221
PK
PK05
Summary of Results of Analyte Ratio Assessment for cys-
mcMMAF (Part 2 MM)
Include Ra(CEOI) and Ra(Ctrough) 
in one table. 95%CI
SAC [A]
4.0223
PK
PK05
Summary of Results of Analyte Ratio Assessment for cys-
mcMMAF (Part 2 NHL)
Include Ra(CEOI) and Ra(Ctrough) 
in one table. 95%CI
SAC
NOTES: 
A. Indicates which displays will be generated for the reporting effort for multiple myeloma


CONFIDENTIAL
BMA117159
211
16.12.11. Pharmacokinetic Figures
Pharmacokinetic: Figures
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Concentration
14.0010
PK
PK16
Individual Plasma GSK2857916 (ADC) Concentration-Time 
Plots (Linear and Semi-Log) (Part 1)
SAC [A]
14.0011
PK
PK16
Individual Plasma GSK2857916 (ADC) Concentration-Time 
Plots (Linear and Semi-Log) (Part 2 MM)
SAC [A]
14.0013
PK
PK16
Individual Plasma GSK2857916 (ADC) Concentration-Time 
Plots (Linear and Semi-Log) (Part 2 NHL)
SAC
14.0020
PK
PK16
Individual Plasma GSK2857916 (Total Antibody) 
Concentration-Time Plots (Linear and Semi-Log) (Part 1)
SAC [A]
14.0021
PK
PK16
Individual Plasma GSK2857916 (Total Antibody) 
Concentration-Time Plots (Linear and Semi-Log) (Part 2 MM)
SAC [A]
14.0023
PK
PK16
Individual Plasma GSK2857916 (Total Antibody) 
Concentration-Time Plots (Linear and Semi-Log) (Part 2 NHL)
SAC
14.0030
PK
PK16
Individual Plasma GSK2857916 (Unbound Antibody) 
Concentration-Time Plots (Linear and Semi-Log) (Part 1)
SAC [A]
14.0031
PK
PK16
Individual Plasma GSK2857916 (Unbound Antibody) 
Concentration-Time Plots (Linear and Semi-Log) (Part 2 MM)
If data was not collected, present “No 
data to report”
SAC [A]
14.0033
PK
PK16
Individual Plasma GSK2857916 (Unbound Antibody) 
Concentration-Time Plots (Linear and Semi-Log) (Part 2 NHL)
If data was not collected, present “No 
data to report”
SAC
14.0040
PK
PK16
Individual Plasma cys-mcMMAF Concentration-Time Plots 
(Linear and Semi-Log) (Part 1)
SAC [A]


CONFIDENTIAL
BMA117159
212
Pharmacokinetic: Figures
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
14.0041
PK
PK16
Individual Plasma cys-mcMMAF Concentration-Time Plots 
(Linear and Semi-Log) (Part 2 MM)
SAC [A]
14.0043
PK
PK16
Individual Plasma cys-mcMMAF Concentration-Time Plots 
(Linear and Semi-Log) (Part 2 NHL)
SAC
14.0050
PK
PK17
Mean Plasma GSK2857916 (ADC) Concentration-Time Plots 
(Linear and Semi-Log) (Part 1)
SAC [A]
14.0051
PK
PK17
Mean Plasma GSK2857916 (ADC) Concentration-Time Plots 
(Linear and Semi-Log) (Part 2 MM)
SAC [A]
14.0053
PK
PK17
Mean Plasma GSK2857916 (ADC) Concentration-Time Plots 
(Linear and Semi-Log) (Part 2 NHL)
SAC
14.0060
PK
PK17
Mean Plasma GSK2857916 (Total Anti-body) Concentration-
Time Plots (Linear and Semi-Log) (Part 1)
SAC [A]
14.0061
PK
PK17
Mean Plasma GSK2857916 (Total Anti-body) Concentration-
Time Plots (Linear and Semi-Log) (Part 2 MM)
SAC [A]
14.0063
PK
PK17
Mean Plasma GSK2857916 (Total Anti-body) Concentration-
Time Plots (Linear and Semi-Log) (Part NHL)
SAC
14.0070
PK
PK17
Mean Plasma GSK2857916 (Unbound Anti-body)
Concentration-Time Plots (Linear and Semi-Log) (Part 1)
SAC [A]
14.0071
PK
PK17
Mean Plasma GSK2857916 (Unbound Anti-body) 
Concentration-Time Plots (Linear and Semi-Log) (Part 2 MM)
If data was not collected, present “No 
data to report”
SAC [A]
14.0073
PK
PK17
Mean Plasma GSK2857916 (Unbound Anti-body) 
Concentration-Time Plots (Linear and Semi-Log) (Part 2 NHL)
If data was not collected, present “No 
data to report”
SAC
14.0080
PK
PK17
Mean Plasma GSK2857916 (cys-mcMMAF) Concentration-
Time Plots (Linear and Semi-Log) (Part 1)
SAC [A]


CONFIDENTIAL
BMA117159
213
Pharmacokinetic: Figures
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
14.0081
PK
PK17
Mean Plasma GSK2857916 (cys-mcMMAF) Concentration-
Time Plots (Linear and Semi-Log) (Part 2 MM)
SAC [A]
14.0083
PK
PK17
Mean Plasma GSK2857916 (cys-mcMMAF) Concentration-
Time Plots (Linear and Semi-Log) (Part 2 NHL)
SAC
14.0090
PK
PK18
Median Plasma GSK2857916 (ADC) Concentration-Time 
Plots (Linear and Semi-Log) (Part 1)
SAC [A]
14.0091
PK
PK18
Median Plasma GSK2857916 (ADC) Concentration-Time 
Plots (Linear and Semi-Log) (Part 2 MM)
SAC [A]
14.0093
PK
PK18
Median Plasma GSK2857916 (ADC) Concentration-Time 
Plots (Linear and Semi-Log) (Part 2 NHL)
SAC
14.0100
PK
PK18
Median Plasma GSK2857916 (Total Anti-body) 
Concentration-Time Plots (Linear and Semi-Log) (Part 1)
SAC [A]
14.0101
PK
PK18
Median Plasma GSK2857916 (Total Anti-body) 
Concentration-Time Plots (Linear and Semi-Log) (Part 2 MM)
SAC [A]
14.0103
PK
PK18
Median Plasma GSK2857916 (Total Anti-body) 
Concentration-Time Plots (Linear and Semi-Log) (Part 2 NHL)
SAC
14.0110
PK
PK18
Median Plasma GSK2857916 (Unbound Anti-body) 
Concentration-Time Plots (Linear and Semi-Log) (Part 1)
SAC [A]
14.0111
PK
PK18
Median Plasma GSK2857916 (Unbound Anti-body) 
Concentration-Time Plots (Linear and Semi-Log) (Part 2 MM)
If data was not collected, present “No 
data to report”
SAC [A]
14.0113
PK
PK18
Median Plasma GSK2857916 (Unbound Anti-body) 
Concentration-Time Plots (Linear and Semi-Log) (Part 2 NHL)
If data was not collected, present “No 
data to report”
SAC
14.0120
PK
PK18
Median Plasma GSK2857916 (cys-mcMMAF) Concentration-
Time Plots (Linear and Semi-Log) (Part 1)
SAC [A]


CONFIDENTIAL
BMA117159
214
Pharmacokinetic: Figures
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
14.0121
PK
PK18
Median Plasma GSK2857916 (cys-mcMMAF) Concentration-
Time Plots (Linear and Semi-Log) (Part 2 MM)
SAC [A]
14.0123
PK
PK18
Median Plasma GSK2857916 (cys-mcMMAF) Concentration-
Time Plots (Linear and Semi-Log) (Part 2 NHL)
SAC
Dose Proportionality
14.0130
PK
LIVER14
Scatter Plot of GSK2857916 (ADC), GSK2857916 (Total 
Antibody), GSK2857916 (Unbound Antibody), and cys-
mcMMAF PK Parameters by Cycle 1 Dose (Part 1)
using log transformed value. for 
AUC(0-tau), Cmax, 
PK Parameter value as y-axis and 
Cycle 1 dose as x-axis; label x-axis 
with dose value. Use the format of 
mock up LIVER14, no reference line 
is needed.
SAC [A]
Accumulation Ratio
14.0140
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(CEOI)and Ro(Ctrough) on 
different plots. Only include 
geometric mean and 95%CI
Plot analytes: ADC, total antibody, 
unbound antibody, and cys-mcMMAF 
on the same plot.
SAC [A]
14.0141
PK
PK28
Plot of Individual (+Geometric Mean and 95%CI) of 
Accumulation Ratios for GSK2857916 Analytes (Linear and 
Semi-Log) (Part 2 MM)
Add a reference line at 1
Plot Ro(CEOI)and Ro(Ctrough) on 
different plots. Only include 
geometric mean and 95%CI
Plot analytes: ADC, total antibody, 
SAC [A]


CONFIDENTIAL
BMA117159
215
Pharmacokinetic: Figures
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
unbound antibody, and cys-mcMMAF 
on the same plot.
14.0142
PK
PK28
Plot of Individual (+Geometric Mean and 95%CI) of 
Accumulation Ratios for GSK2857916 Analytes (Linear and 
Semi-Log) (Part 2 NHL)
Add a reference line at 1
Plot Ro(CEOI)and Ro(Ctrough) on 
different plots. Only include 
geometric mean and 95%CI
Plot analytes: ADC, total antibody, 
unbound antibody, and cys-mcMMAF 
on the same plot.
SAC
Analyte Ratio
14.0180
PK
PK_F1
Plot of Geometric Mean and 95%CI of Analyte Ratios for 
GSK2857916 Analytes by cycle (Linear and Semi-Log) (Part 
1)
See example in Page 6 of 
By dose
Plot Ra(CEOI) and Ra(Ctrough) on 
the same plot.
Use “Analyte Ratio to ADC” as y-axis 
label
C(x) predose = C(x-1)trough 
SAC [A]
14.0181
PK
PK_F1
Plot of Geometric Mean and 95%CI of Analyte Ratios for 
GSK2857916 Analytes by cycle (Linear and Semi-Log) (Part 2 
SAC [A]
PPD


CONFIDENTIAL
BMA117159
216
Pharmacokinetic: Figures
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
MM)
14.0182
PK
PK_F1
Plot of Geometric Mean and 95%CI of Analyte Ratios for 
GSK2857916 Analytes by cycle (Linear and Semi-Log) (Part 2 
NHL)
SAC
NOTES: 
A. Indicates which displays will be generated for the reporting effort for multiple myeloma


CONFIDENTIAL
BMA117159
217
16.12.12. Pharmacokinetic / Pharmacodynamic (and / or Biomarker) Figures
Pharmacokinetic / Pharmacodynamic: Figures
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
16.0010
PK/PD
PK_F2
Plot of Fridericia’s QTc Change from Baseline versus PK 
Concentration for GSK2857916 (ADC) (MM)
SAC [A]
16.0011
PK/PD
PK_F2
Plot of Fridericia’s QTc Change from Baseline versus PK 
Concentration for GSK2857916 (ADC) (NHL)
SAC
16.0020
PK/PD
PK_F2
Plot of Fridericia’s QTc Change from Baseline versus PK 
Concentration for GSK2857916 (Total Antibody) (MM)
SAC [A]
16.0021
PK/PD
PK_F2
Plot of Fridericia’s QTc Change from Baseline versus PK 
Concentration for GSK2857916 (Total Antibody) (NHL)
SAC
16.0030
PK/PD
PK_F2
Plot of Fridericia’s QTc Change from Baseline versus PK 
Concentration for GSK2857916 (Unbound Antibody) (MM)
SAC [A]
16.0031
PK/PD
PK_F2
Plot of Fridericia’s QTc Change from Baseline versus PK 
Concentration for GSK2857916 (Unbound Antibody) (NHL)
If data was not collected, present “No 
data to report”
SAC
16.0040
PK/PD
PK_F2
Plot of Fridericia’s QTc Change from Baseline versus PK 
Concentration for cys-mcMMAF (MM)
SAC [A]
16.0041
PK/PD
PK_F2
Plot of Fridericia’s QTc Change from Baseline versus PK 
Concentration for cys-mcMMAF (NHL)
SAC
NOTES: 
A. Indicates which displays will be generated for the reporting effort for multiple myeloma


CONFIDENTIAL
BMA117159
218
16.12.13. ICH Listings
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Subject Disposition
1.0010
All Treated
ES2
Listing of Reasons for Study Withdrawal (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0011
All Treated
ES2
Listing of Reasons for Study Withdrawal (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
1.0020
All Treated
CP_RA1p
Listing of Planned and Actual Treatments (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0021
All Treated
CP_RA1p
Listing of Planned and Actual Treatments (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
1.0030
All Treated
SD2
Listing of Reasons for Study Treatment Discontinuation (All 
Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0031
All Treated
SD2
Listing of Reasons for Study Treatment Discontinuation (Part 2 
NHL)
Report for sub-population: Part 2 
NHL.
SAC
Protocol Deviations
1.0040
All Treated
DV2
Listing of Important Protocol Deviations (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0041
All Treated
DV2
Listing of Important Protocol Deviations (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
1.0050
All Treated
IE3
Listing of Subjects with Inclusion/Exclusion Criteria Deviations 
(All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0051
All Treated
IE3
Listing of Subjects with Inclusion/Exclusion Criteria Deviations 
(Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC


CONFIDENTIAL
BMA117159
219
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Populations Analysed
1.0060
All Treated
SA3a
Listing of Subjects Excluded from Any Population (All Treated 
MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0061
All Treated
SA3a
Listing of Subjects Excluded from Any Population (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
Demographic and Baseline Characteristics
1.0070
All Treated
DM2
Listing of Demographic Characteristics (All Treated MM)
Report for sub-population: All 
Treated MM. Add BMI (kg/m2).
SAC [A]
1.0071
All Treated
DM2
Listing of Demographic Characteristics (Part 2 NHL)
Report for sub-population: Part 2 
NHL. Add BMI (kg/m2).
SAC
1.0080
All Treated
DM9
Listing of Race (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0081
All Treated
DM9
Listing of Race (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
Prior and Concomitant Medications
1.0620
All Treated
OCM1A
Listing of Concomitant Medications (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0621
All Treated
OCM1A
Listing of Concomitant Medications (Part 2 NHL)
Report for sub-population: Part 2
NHL.
SAC


CONFIDENTIAL
BMA117159
220
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Exposure and Treatment Compliance
1.0090
All Treated
OEX8A
Listing of Exposure Data (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0091
All Treated
OEX8A
Listing of Exposure Data (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
1.0100
All Treated
ODMOD10A
Listing of Dose Reductions (All Treated MM)
Report for sub-population: All 
Treated MM. Include Planned 
Time. 
SAC [A]
1.0101
All Treated
ODMOD10A
Listing of Dose Reductions (Part 2 NHL)
Report for sub-population: All 
Treated MM. Include Planned 
Time. 
SAC
1.0110
All Treated
ODMOD12A
Listing of Dose Delays (All Treated MM)
Report for sub-population: All 
Treated MM. Include Planned 
Time. IDSL standard does not 
report demographic info.  
to check with 
regarding planned time and 
cycle day. If it is too much 
programming work to change now, 
we can keep it as it is.
SAC [A]
PPD
PPD
PPD


CONFIDENTIAL
BMA117159
221
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0111
All Treated
ODMOD12A
Listing of Dose Delays (Part 2 NHL)
Report for sub-population: All 
Treated MM. Include Planned 
Time. IDSL standard does not 
report demographic info.  
to check with 
regarding planned time and 
cycle day. If it is too much 
programming work to change now, 
we can keep it as it is.
SAC
1.0120
All Treated
ODMOD15A
Listing of Dose Escalations (All Treated MM)
Report for sub-population: All 
Treated MM. Include 
Age(y)/Sex/Race, Cycle, Visit.
For C2MD, list the dose 
escalations where a dose 
escalation is indicated in the data –
from the site.
SAC [A]
1.0121
All Treated
ODMOD15A
Listing of Dose Escalations (Part 2 NHL)
Report for sub-population: All 
Treated MM. Include 
Age(y)/Sex/Race, Cycle, Visit.
For C2MD, list the dose 
escalations where a dose 
escalation is indicated in the data –
from the site.
SAC
1.0490
All Treated
ODMOD14A
Listing of Incomplete Infusions (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0491
All Treated
ODMOD14A
Listing of Incomplete Infusions (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
PPD
PPD
PPD


CONFIDENTIAL
BMA117159
222
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0500
All Treated
ODMOD17A
Listing of Infusion Interruptions (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0501
All Treated
ODMOD17A
Listing of Infusion Interruptions (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
Adverse Events
1.0140
All Treated
OAE04
Listing of All Adverse Events (All Treated MM)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
SAC [A]
1.0141
All Treated
OAE04
Listing of All Adverse Events (Part 2 NHL)
Report for population subgroup: 
Part 2 NHL. Remove onset cycle 
and cycle day from all AE related 
listings.
SAC
1.0150
All Treated
OAE03
Listing of Subject Numbers for Individual Adverse Events (All 
Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0151
All Treated
OAE03
Listing of Subject Numbers for Individual Adverse Events (Part 
2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
1.0160
All Treated
AE2
Listing of Relationship Between Adverse Event System Organ 
Classes, Preferred Terms, and Verbatim Text (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0161
All Treated
AE2
Listing of Relationship Between Adverse Event System Organ 
Classes, Preferred Terms, and Verbatim Text (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC


CONFIDENTIAL
BMA117159
223
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Serious and Other Significant Adverse Events
1.0180
All Treated
OAE04
Listing of Fatal Serious Adverse Events (All Treated MM)
Report for sub-population: All 
Treated MM. Include column to 
indicate relationship to study 
treatment.
SAC [A]
1.0181
All Treated
OAE04
Listing of Fatal Serious Adverse Events (Part 2 NHL)
Report for sub-population: All 
Treated MM. Include column to 
indicate relationship to study 
treatment.
SAC
1.0190
All Treated
OAE04
Listing of Non-Fatal Serious Adverse Events (All Treated MM)
Report for sub-population: All 
Treated MM. Include column to 
indicate relationship to study 
treatment.
SAC [A]
1.0191
All Treated
OAE04
Listing of Non-Fatal Serious Adverse Events (Part 2 NHL)
Report for sub-population: All 
Treated MM. Include column to 
indicate relationship to study 
treatment.
SAC
1.0460
All Treated
AE14
Listing of Reasons for Considering as a Serious Adverse Event 
(All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0461
All Treated
AE14
Listing of Reasons for Considering as a Serious Adverse Event 
(Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
1.0470
All Treated
OAE04
Listing of Adverse Events Leading to Withdrawal from Study / 
Permanent Discontinuation of Study Treatment (All Treated 
MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0471
All Treated
OAE04
Listing of Adverse Events Leading to Withdrawal from Study / 
Permanent Discontinuation of Study Treatment (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC


CONFIDENTIAL
BMA117159
224
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0200
All Treated
OAE04
Listing of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment (All Treated MM)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
SAC [A]
1.0201
All Treated
OAE04
Listing of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment (Part 2 NHL)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
SAC
1.0210
All Treated
OAE04
Listing of Dose-Limiting Adverse Events (All Treated MM)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
SAC [A]
1.0220
DLT 
Evaluable
DL3
Listing of Dose-Limiting Toxicities during the Determinative
Period (Day 1-21) (Part 1) 
Report for population subgroup: 
Part 1
SAC [A]
1.0240
All Treated
OAE04
Listing of Adverse Events Leading to Dose Reduction (All 
Treated MM)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
SAC [A]
1.0241
All Treated
OAE04
Listing of Adverse Events Leading to Dose Reduction (Part 2 
NHL)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
SAC
1.0250
All Treated
OAE04
Listing of Adverse Events Leading to Dose Interruptions or 
Delays (All Treated MM)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
SAC [A]


CONFIDENTIAL
BMA117159
225
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0251
All Treated
OAE04
Listing of Adverse Events Leading to Dose Interruptions or 
Delays (Part 2 NHL)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
SAC
1.0510
All Treated
OAE04
Listing of Adverse Events Leading to Incomplete Infusions (All 
Treated MM)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
SAC [A]
1.0511
All Treated
OAE04
Listing of Adverse Events Leading to Incomplete Infusions (Part 
2 NHL)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
SAC
1.0520
All Treated
OAE04
Listing of Adverse Events Leading to Infusion Interruptions (All 
Treated MM)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
SAC [A]
1.0521
All Treated
OAE04
Listing of Adverse Events Leading to Infusion Interruptions 
(Part 2 NHL)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
SAC
1.0270
All Treated
OAE04
Listing of Corneal Events (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0271
All Treated
OAE04
Listing of Corneal Events (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
1.0530
All Treated
OAE04
Listing of Thrombocytopenia (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]


CONFIDENTIAL
BMA117159
226
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0531
All Treated
OAE04
Listing of Thrombocytopenia (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
1.0540
All Treated
OAE04
Listing of Hematologic Toxicity (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0541
All Treated
OAE04
Listing of Hematologic Toxicity (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
1.0550
All Treated
OAE04
Listing of Neutropenia (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0551
All Treated
OAE04
Listing of Neutropenia (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
1.0260
All Treated
OAE04
Listing of Infusion Related Reactions (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0261
All Treated
OAE04
Listing of Infusion Related Reactions (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
Hepatobiliary (Liver)
1.0410
All Treated
MH2
Listing of Medical Conditions for Subjects with Liver Stopping 
Events (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0411
All Treated
MH2
Listing of Medical Conditions for Subjects with Liver Stopping 
Events (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
1.0420
All Treated
SU2
Listing of Substance Use for Subjects with Liver Stopping 
Events (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0421
All Treated
SU2
Listing of Substance Use for Subjects with Liver Stopping 
Events (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC


CONFIDENTIAL
BMA117159
227
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
All Laboratory
1.0330
All Treated
OLB7
Listing of All Laboratory Data for Subjects with Any Value of 
Potential Clinical Importance (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0331
All Treated
OLB7
Listing of All Laboratory Data for Subjects with Any Value of 
Potential Clinical Importance (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
1.0320
All Treated
OLB13
Listing of Laboratory Data with Character Results (All Treated 
MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0321
All Treated
OLB13
Listing of Laboratory Data with Character Results (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
1.0350
All Treated
UR2A
Listing of Urinalysis Data for Subjects with Any Value of 
Potential Clinical Importance (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0351
All Treated
UR2A
Listing of Urinalysis Data for Subjects with Any Value of 
Potential Clinical Importance (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
ECOG Performance Status
1.0430
All Treated
PS5A
Listing of ECOG Performance Status (All Treated MM)
Report for sub-population: Part 2 
NHL.
SAC [A]
1.0431
All Treated
PS5A
Listing of ECOG Performance Status (Part 2 NHL)
Report for sub-population: All 
Treated MM.
SAC
Response
1.0560
All Treated
RE5
Listing of Investigator-Assessed Responses (All Treated MM)
Report for sub-population: All 
Treated MM. List investigator 
reported response by visit.
SAC [A]


CONFIDENTIAL
BMA117159
228
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0561
All Treated
RE5
Listing of Investigator-Assessed Responses (Part 2 NHL)
Report for sub-population: Part 2 
NHL.List investigator reported 
response by visit.
SAC
Time-to-Event Endpoints
1.0440
All Treated
TTE9
Listing of Progression-Free Survival (All Treated MM)
Report for sub-population: All 
Treated MM. Keep all optional 
columns. Use 'First Dose Date' in 
place of 'Randomization Date'. 
Example for endpoint description: 
Censor: Last adequate asmt, 
Event: Died, etc. Use months as 
unit.
SAC [A]
1.0570
All Treated
TTE9
Listing of Duration of Response (All Treated MM) 
Report for sub-population: All 
Treated MM. Keep all optional 
columns. Use 'First Dose Date' in 
place of 'Randomization Date'. 
Example for endpoint description: 
Censor: Last adequate asmt, 
Event: Died, etc. Use months as 
unit.
SAC [A]


CONFIDENTIAL
BMA117159
229
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0580
All Treated
TTE9
Listing of Overall Survival (All Treated MM) 
Report for sub-population: All 
Treated MM. Keep all optional 
columns. Use 'First Dose Date' in 
place of 'Randomization Date'. 
Example for endpoint description: 
Censor: Last adequate asmt, 
Event: Died, etc. If all patients can 
be reconsented.
SAC
1.0590
All Treated
TTE9
Listing of Time to Progression (All Treated MM) 
Report for sub-population: All 
Treated MM. Keep all optional 
columns. Use 'First Dose Date' in 
place of 'Randomization Date'. 
Example for endpoint description: 
Censor: Last adequate asmt, 
Event: Died, etc. Use months as 
unit.
SAC [A]
1.0600
All Treated
TTE9
Listing of Time to Response (All Treated MM) 
Report for sub-population: All 
Treated MM. Keep all optional 
columns. Use 'First Dose Date' in 
place of 'Randomization Date'. 
Example for endpoint description: 
Censor: Last adequate asmt, 
Event: Died, etc. Use months as 
unit.
SAC [A]


CONFIDENTIAL
BMA117159
230
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0610
All Treated
TTE9
Listing of Time to Best Response (All Treated MM) 
Report for sub-population: All 
Treated MM. Keep all optional 
columns. Use 'First Dose Date' in 
place of 'Randomization Date'. 
Example for endpoint description: 
Censor: Last adequate asmt, 
Event: Died, etc. Use months as 
unit.
SAC [A]
Death
1.0390
All Treated
DTH3
Listing of Deaths (All Treated MM)
Report for sub-population: All 
Treated MM. include the time from 
last dose in the listing and Number 
of Cycles/Last Dose (optional 
columns in DTH3). 
SAC [A]
1.0391
All Treated
DTH3
Listing of Deaths (Part 2 NHL)
Report for sub-population: Part 2 
NHL. include the time from last 
dose in the listing and Number of 
Cycles/Last Dose (optional 
columns in DTH3).
SAC
PK
1.0630
PK
PK07
Listing of Plasma GSK2857916 (ADC) Pharmacokinetic 
Concentration-Time Data (MM)
SAC [A]
1.0631
PK
PK07
Listing of Plasma GSK2857916 (ADC) Pharmacokinetic 
Concentration-Time Data (NHL)
SAC
1.0640
PK
PK07
Listing of Plasma GSK2857916 (Total Antibody) 
Pharmacokinetic Concentration-Time Data (MM)
SAC [A]


CONFIDENTIAL
BMA117159
231
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0641
PK
PK07
Listing of Plasma GSK2857916 (Total Antibody) 
Pharmacokinetic Concentration-Time Data (NHL)
SAC
1.0650
PK
PK07
Listing of Plasma GSK2857916 (Unbound Antibody) 
Pharmacokinetic Concentration-Time Data (MM)
SAC [A]
1.0651
PK
PK07
Listing of Plasma GSK2857916 (Unbound Antibody) 
Pharmacokinetic Concentration-Time Data (NHL)
SAC
1.0660
PK
PK07
Listing of Plasma cys-mcMMAF Pharmacokinetic 
Concentration-Time Data (MM)
SAC [A]
1.0661
PK
PK07
Listing of Plasma cys-mcMMAF Pharmacokinetic 
Concentration-Time Data (NHL)
SAC
1.0710
PK
PK15
Listing of GSK2857916 (ADC) CEOI and Ctrough Accumulation 
Ratio (MM)
SAC [A]
1.0711
PK
PK15
Listing of GSK2857916 (ADC) CEOI and Ctrough Accumulation 
Ratio (NHL)
SAC
1.0720
PK
PK15
Listing of GSK2857916 (Total Antibody) CEOI and Ctrough 
Accumulation Ratio (MM)
SAC [A]
1.0721
PK
PK15
Listing of GSK2857916 (Total Antibody) CEOI and Ctrough 
Accumulation Ratio (NHL)
SAC
1.0730
PK
PK15
Listing of GSK2857916 (Unbound Antibody) CEOI and Ctrough 
Accumulation Ratio (MM)
SAC [A]
1.0731
PK
PK15
Listing of GSK2857916 (Unbound Antibody) CEOI and Ctrough 
Accumulation Ratio (NHL)
SAC
1.0740
PK
PK15
Listing of cys-mcMMAF CEOI and Ctrough Accumulation Ratio 
(MM)
SAC [A]


CONFIDENTIAL
BMA117159
232
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0741
PK
PK15
Listing of cys-mcMMAF CEOI and Ctrough Accumulation Ratio 
(NHL)
SAC
NOTES: 
A. Indicates which displays will be generated for the reporting effort for multiple myeloma


CONFIDENTIAL
BMA117159
233
16.12.14. Non-ICH Listings
Non-ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Medical Conditions
30.0010
All Treated
MH2
Listing of Past Cancer-Related and Non-Cancer Related 
Medical Conditions (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0011
All Treated
MH2
Listing of Past Cancer-Related and Non-Cancer Related 
Medical Conditions (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
30.0020
All Treated
MH2
Listing of Current Cancer-Related and Non-Cancer Related 
Medical Conditions (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0021
All Treated
MH2
Listing of Current Cancer-Related and Non-Cancer Related 
Medical Conditions (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
Concomitant Medications
30.0310
All Treated
OCM1A
Listing of Prophylactic Medication for Infusion-Related 
Reactions (All Treated MM)
Report for sub-population: All 
Treated MM. Please replace the 
2nd column as ‘Drug Class/Drug 
Name’ and the last column as 
‘Reason for Medication’ 
SAC [A]
30.0311
All Treated
OCM1A
Listing of Prophylactic Medication for Infusion-Related 
Reactions (Part 2 NHL)
Report for sub-population: Part 2 
NHL. Please replace the 2nd 
column as ‘Drug Class/Drug 
Name’ and the last column as 
‘Reason for Medication’ 
SAC
30.0320
All Treated
OCM1A
Listing of Eye Medications (All Treated MM)
Report for sub-population: All 
Treated MM. Please replace the 
2nd column as ‘Drug Class/Drug 
Name’ and the last column as 
SAC [A]


CONFIDENTIAL
BMA117159
234
Non-ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
‘Reason for Medication’
30.0321
All Treated
OCM1A
Listing of Eye Medications (Part 2 NHL)
Report for sub-population: Part 2 
NHL. Please replace the 2nd 
column as ‘Drug Class/Drug 
Name’ and the last column as 
‘Reason for Medication’
SAC
Blood and Blood Supportive Care Products
30.0380
All Treated
BP4
Listing of Blood Products (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0381
All Treated
BP4
Listing of Blood Products (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
30.0390
All Treated
BP5
Listing of Blood Supportive Care Products (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0391
All Treated
BP5
Listing of Blood Supportive Care Products (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
Substance Use
30.0370
All Treated
SU2
Listing of Substance Use (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0371
All Treated
SU2
Listing of Substance Use (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
Anti-Cancer Therapy, Radiotherapy and Surgical Procedures
30.0040
All Treated
AC6
Listing of Prior Anti-Cancer Therapy (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0041
All Treated
AC6
Listing of Prior Anti-Cancer Therapy (Part 2 NHL)
Report for sub-population: Part 2 
SAC


CONFIDENTIAL
BMA117159
235
Non-ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
NHL.
30.0050
All Treated
AC7
Listing of Anti-Cancer Radiotherapy (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0051
All Treated
AC7
Listing of Anti-Cancer Radiotherapy (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
30.0060
All Treated
OSP3
Listing of Prior/On Treatment Cancer and Non-Cancer 
Related Surgical Procedures (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0061
All Treated
OSP3
Listing of Prior/On Treatment Cancer and Non-Cancer 
Related Surgical Procedures (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
30.0400
All Treated
FAC3
Listing of Follow-Up Anti-Cancer Therapy (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0401
All Treated
FAC3
Listing of Follow-Up Anti-Cancer Therapy (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
Disease Characteristics
30.0080
All Treated
DC4
Listing of Disease Characteristics at Screening (All Treated 
MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0081
All Treated
DC4
Listing of Disease Characteristics at Screening (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
30.0360
All Treated
DC3
Listing of Disease Characteristics at Initial Diagnosis (All 
Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0361
All Treated
DC3
Listing of Disease Characteristics at Initial Diagnosis (Part 2 
NHL)
Report for sub-population: Part 2 
NHL.
SAC
30.0290
All Treated
OLB7
Listing of Genetic Characteristics (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]


CONFIDENTIAL
BMA117159
236
Non-ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
30.0300
All Treated
SAFE_L1
Listing of Disease Characteristics, Prior Treatment, Dose 
Modification and Response to GSK2857916 (Part 2 MM) 
Report for sub-population: Part 2
MM. Provide a line listing by 
patient with subject identifier, 
ISS stage at screening, number 
of prior lines of therapy, 
refractory to last line of therapy 
(Y/N), prior use of daratumumab 
(Y/N), refractory to both  IMID 
and PI (Y/N), Best confirmed 
response, 
SAC [A]
Exposure
30.0130
All Treated
OEX9
Summary Listing of Overall Exposure and Dose Modifications 
(All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0131
All Treated
OEX9
Summary Listing of Overall Exposure and Dose Modifications 
(Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
Adverse Events
30.0540
All Treated
OAE4
Listing of Serious Adverse Events (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0541
All Treated
OAE4
Listing of Serious Adverse Events (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
30.0550
All Treated
OAE04
Listing of Drug-Related Adverse Events (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0551
All Treated
OAE04
Listing of Drug-Related Adverse Events (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
30.0560
All Treated
OAE4
Listing of Drug-Related Serious Adverse Events (All Treated 
Report for sub-population: All 
SAC [A]


CONFIDENTIAL
BMA117159
237
Non-ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
MM)
Treated MM.
30.0561
All Treated
OAE4
Listing of Drug-Related Serious Adverse Events (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
30.0450
All Treated
AE2
Listing of Relationship Between SOC and Verbatim Text for 
AEs Collapsed to Corneal Events 
SAC [A]
30.0460
All Treated
AE2
Listing of Relationship Between SOC and Verbatim Text for 
AEs Collapsed to Thrombocytopenia 
SAC [A]
30.0470
All Treated
AE2
Listing of Relationship Between SOC and Verbatim Text for 
AEs Collapsed to Neutrupenia 
SAC [A]
30.0480
All Treated
AE2
Listing of Relationship Between SOC and Verbatim Text for 
AEs Collapsed to Hematologic Toxicity 
SAC [A]
30.0490
All Treated
AE2
Listing of Relationship Between SOC and Verbatim Text for 
AEs Collapsed to Infusion related reactions 
SAC [A]
Deaths
30.0570
All Treated
DTH5
Listing of Subject Numbers for Specific Causes of Deaths (All 
Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0571
All Treated
DTH5
Listing of Subject Numbers for Specific Causes of Deaths 
(Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
Laboratory
30.0530
All Treated
OLB7
Listing of Grade 3 and Grade 4 Laboratory Data (All Treated 
MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0531
All Treated
OLB7
Listing of Grade 3 and Grade 4 Laboratory Data (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
30.0580
All Treated
LIVER13
Listing of Subjects Meeting Hepatobiliary Laboratory Criteria 
Report for sub-population: All 
SAC [A]


CONFIDENTIAL
BMA117159
238
Non-ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Post-Baseline (All Treated MM)
Treated MM.
30.0581
All Treated
LIVER13
Listing of Subjects Meeting Hepatobiliary Laboratory Criteria 
Post-Baseline (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
30.0160
All Treated
LIVER5
Listing of Liver Monitoring/Stopping Event Reporting (All 
Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0161
All Treated
LIVER5
Listing of Liver Monitoring/Stopping Event Reporting (Part 2 
NHL)
Report for sub-population: Part 2 
NHL.
SAC
Constitutional Symptoms and Organ Examinations
30.0510
All Treated
OCS3
Listing of Constitutional Symptoms (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
30.0520
All Treated
OOE2
Listing of Organ Examinations (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
Left Ventricular Ejection Fraction
30.0500
All Treated
OLVEF2A
Listing of Left Ventricular Ejection Fraction Results (All 
Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0501
All Treated
OLVEF2A
Listing of Left Ventricular Ejection Fraction Results (Part 2 
NHL)
Report for sub-population: Part 2 
NHL.
SAC
ECG
30.0140
All Treated
OECG5A
Listing of Fridericia’s QTc Values of Potential Clinical 
Importance (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0141
All Treated
OECG5A
Listing of Fridericia’s QTc Values of Potential Clinical 
Importance (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
Vital Signs
30.0440
All Treated
OVT7A
Listing of Vital Sign Values of Potential Clinical Importance 
Report for sub-population: All 
SAC [A]


CONFIDENTIAL
BMA117159
239
Non-ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
(All Treated MM)
Treated MM.
30.0441
All Treated
OVT7A
Listing of Vital Sign Values of Potential Clinical Importance 
(Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
Ocular Exam
30.0260
All Treated
SAFE_L2
Listing of Visual Acuity and Abnormal Corneal Exam Results 
(All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0261
All Treated
SAFE_L2
Listing of Visual Acuity and Abnormal Corneal Exam Results 
(Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
30.0330
All Treated
SAFE_L2
Listing of Abnormal Conjunctival Exam Results (All Treated 
MM)
Report for sub-population: All 
Treated MM. Please include 
screening results and any post-
baseline abnormal results for 
each patient. Include: Centre ID/
Subj., Age(y)/ Sex/ Race, 
Reported Corneal Events (Y/N), 
Cycle/Visit, Time Since 1st 
Dose/ Time Since last Dose, 
Eye, Exam Test, Result
SAC [A]
30.0331
All Treated
SAFE_L2
Listing of Abnormal Conjunctival Exam Results (Part 2 NHL)
Report for sub-population: Part 2 
NHL. Please include screening 
results and any post-baseline 
abnormal results for each 
patient. Include: Centre ID/
Subj., Age(y)/ Sex/ Race, 
Reported Corneal Events (Y/N), 
Cycle/Visit, Time Since 1st 
Dose/ Time Since last Dose, 
SAC


CONFIDENTIAL
BMA117159
240
Non-ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Eye, Exam Test, Result
30.0340
All Treated
SAFE_L2
Listing of Abnormal Slit Lamp Anterior Chamber and Slit 
Lamp Lens Exam Results (All Treated MM)
Report for sub-population: All 
Treated MM. Please include 
screening results and any post-
baseline abnormal results for 
each patient. Include: Centre ID/
Subj., Age(y)/ Sex/ Race, 
Reported Corneal Events (Y/N), 
Cycle/Visit, Time Since 1st 
Dose/ Time Since last Dose, 
Eye, Exam Test, Result
SAC [A]
30.0341
All Treated
SAFE_L2
Listing of Abnormal Slit Lamp Anterior Chamber and Slit 
Lamp Lens Exam Results (Part 2 NHL)
Report for sub-population: Part 2 
NHL. Please include screening 
results and any post-baseline 
abnormal results for each 
patient. Include: Centre ID/
Subj., Age(y)/ Sex/ Race, 
Reported Corneal Events (Y/N), 
Cycle/Visit, Time Since 1st 
Dose/ Time Since last Dose, 
Eye, Exam Test, Result
SAC
30.0350
All Treated
SAFE_L2
Listing of Indirect Fundoscopic Exam and Intraocular 
Pressure Results (All Treated MM)
Report for sub-population: All 
Treated MM. Include: Centre ID/
Subj., Age(y)/ Sex/ Race, 
Reported Corneal Events (Y/N), 
Cycle/Visit, Time Since 1st 
Dose/ Time Since last Dose, 
Eye, Exam Test, Result
SAC [A]


CONFIDENTIAL
BMA117159
241
Non-ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
30.0351
All Treated
SAFE_L2
Listing of Indirect Fundoscopic Exam and Intraocular 
Pressure Results (Part 2 NHL)
Report for sub-population: Part 2 
NHL. Include: Centre ID/ Subj., 
Age(y)/ Sex/ Race, Reported 
Corneal Events (Y/N), 
Cycle/Visit, Time Since 1st 
Dose/ Time Since last Dose, 
Eye, Exam Test, Result
SAC
Health Outcomes
30.0590
All Treated
VS4
Listing of Symptom Impact and HRQoL Item Scores (All 
Treated MM)
Report for sub-population: All 
Treated MM. Use the format of 
VS4, use collected visit dates. 
List scores for Bone Pain Worst, 
Bone Pain Average, Fatigue
SAC [A]
30.0591
All Treated
VS4
Listing of Symptom Impact and HRQoL Item Scores (Part 2 
NHL)
Report for sub-population: Part 2 
NHL. Use the format of VS4, use 
collected visit dates. List scores 
for Bone Pain Worst, Bone Pain 
Average, Fatigue
SAC
30.0600
All Treated
VS4
Listing of NEI-VFQ-25 Scores (All Treated MM)
Report for sub-population: All 
Treated MM. Use the format of 
VS4, use collected visit dates. 
List overall composite score and 
11 sub-scores.
SAC [A]
30.0601
All Treated
VS4
Listing of NEI-VFQ-25 Scores (Part 2 NHL)
Report for sub-population: Part 2 
NHL. Use the format of VS4, use 
collected visit dates. List overall 
composite score and 11 sub-
SAC


CONFIDENTIAL
BMA117159
242
Non-ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
scores.
30.0610
All Treated
VS4
Listing of OSDI Scores (All Treated MM)
Report for sub-population: All 
Treated MM. Use the format of 
VS4, use collected visit dates. 
List total score and 3 sub-
scores.
SAC [A]
30.0611
All Treated
VS4
Listing of OSDI Scores (Part 2 NHL)
Report for sub-population: Part 2 
NHL. Use the format of VS4, use 
collected visit dates. List total 
score and 3 sub-scores.
SAC
Anti-Drug Antibody
30.0620
All Treated
SAFE_L3
Listing of Anti-GSK2857916 antibody results (All Treated 
MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0621
All Treated
SAFE_L3
Listing of Anti-GSK2857916 antibody results (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
PK
30.0630
PK
SAS Output of Results of Dose Proportionality Analysis 
Using Power Model 
SAC [A]
30.0640
PK
PK15
Listing of GSK2857916 (Total Antibody) CEOI and Ctrough 
Analyte Ratio (MM)
SAC [A]
30.0641
PK
PK15
Listing of GSK2857916 (Total Antibody) CEOI and Ctrough 
Analyte Ratio (NHL)
SAC
30.0650
PK
PK15
Listing of GSK2857916 (Unbound Antibody) CEOI and 
Ctrough Analyte Ratio (MM)
SAC [A]
30.0651
PK
PK15
Listing of GSK2857916 (Unbound Antibody) CEOI and 
SAC


CONFIDENTIAL
BMA117159
243
Non-ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Ctrough Analyte Ratio (NHL)
30.0660
PK
PK15
Listing of cys-mcMMAF CEOI and Ctrough Analyte Ratio 
(MM)
SAC [A]
30.0661
PK
PK15
Listing of cys-mcMMAF CEOI and Ctrough Analyte Ratio 
(NHL)
SAC
PKPD
30.0690
PKPD
Listing of Fridericia’s QTc Change from Baseline and 
GSK2857916 (ADC) Pharmacokinetic Concentration-Time 
Data (MM)
List QTc change from baseline 
concentration for each visit
SAC [A]
30.0691
PKPD
Listing of Fridericia’s QTc Change from Baseline and 
GSK2857916 (ADC) Pharmacokinetic Concentration-Time 
Data (NHL)
List QTc change from baseline 
concentration for each visit
SAC
30.0700
PKPD
Listing of Fridericia’s QTc Change from Baseline and 
GSK2857916 (Total Antibody) Pharmacokinetic 
Concentration-Time Data (MM)
List QTc change from baseline 
concentration for each visit
SAC [A]
30.0701
PKPD
Listing of Fridericia’s QTc Change from Baseline and 
GSK2857916 (Total Antibody) Pharmacokinetic 
Concentration-Time Data (NHL)
List QTc change from baseline 
concentration for each visit
SAC
30.0710
PKPD
Listing of Fridericia’s QTc Change from Baseline and 
GSK2857916 (Unbound Antibody) Pharmacokinetic 
Concentration-Time Data (MM)
List QTc change from baseline 
concentration for each visit
SAC [A]
30.0711
PKPD
Listing of Fridericia’s QTc Change from Baseline and 
GSK2857916 (Unbound Antibody) Pharmacokinetic 
Concentration-Time Data (NHL)
List QTc change from baseline 
concentration for each visit
SAC
30.0720
PKPD
Listing of Fridericia’s QTc Change from Baseline and cys-
List QTc change from baseline 
SAC [A]


CONFIDENTIAL
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244
Non-ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
mcMMAF Pharmacokinetic Concentration-Time Data (MM)
concentration for each visit
30.0721
PKPD
Listing of Fridericia’s QTc Change from Baseline and cys-
mcMMAF Pharmacokinetic Concentration-Time Data (NHL)
List QTc change from baseline 
concentration for each visit
SAC
NOTES: 
A. Indicates which displays will be generated for the reporting effort for multiple myeloma


CONFIDENTIAL
BMA117159
245
16.13.
Appendix 13: Example Mock Shells for Data Displays
Example: POP_T1
Protocol: BMA117159                                                                             Page 1 of 1
Population: Part 1                                                           (Data as of: 30MAY2001)
Table x.xxxx
Summary of Genetic Characteristics at Screening for Multiple Myeloma Subjects (Part 1)
0.03 mg/kg
0.06 mg/kg
Total
Genetics
(N=100)
(N=100)
(N=200)
del13
5 (5%)
5 (5%)
10 (5%)
del17p13
5 (5%)
5 (5%)
10 (5%)
t(11:14)
5 (5%)
5 (5%)
10 (5%)
t(4:14)
5 (5%)
5 (5%)
10 (5%)
1q21
5 (5%)
5 (5%)
10 (5%)
Other
5 (5%)
5 (5%)
10 (5%)
Missing
5 (5%)
5 (5%)
10 (5%)
PPD


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246
Example: POP_T2
Protocol: BMA117159                                                                             Page 1 of 1
Population: Part 1                                                           (Data as of: 30MAY2001)
Table x.xxxx
Summary of Cytogenetics Risk at Screening (Part 1)
0.03 mg/kg
0.06 mg/kg
Total
Genetics
(N=100)
(N=100)
(N=200)
High Risk [1]
5 (5%)
5 (5%)
10 (5%)
Other (non-high 
risk, not done, or 
missing)
5 (5%)
5 (5%)
10 (5%)
[1] A subject is considered as high risk if the subject has any of the following cytogenetics:
t(4;14), del17p, t(14;16).
PPD


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247
Example: POP_T3
Protocol: BMA117159                                                                             Page 1 of 1
Population: Part 1                        
(Data as of: 30MAY2001)
Table x.xxxx
Summary of Prior Anti-Cancer Therapy by Drug Class of Agents for Multiple Myeloma Subjects (Part 1)
0.03 mg/kg
0.06 mg/kg
Total
Drug Class
(N=100)
(N=100)
(N=200)
Steroids
5 (5%)
5 (5%)
10 (5%)
Immunomodulator (IMID)
5 (5%)
5 (5%)
10 (5%)
LENALIDOMIDE
5 (5%)
5 (5%)
10 (5%)
POMALIDOMIDE
5 (5%)
5 (5%)
10 (5%)
THALIDOMIDE
5 (5%)
5 (5%)
10 (5%)
Proteasome Inhibitor (PI)
5 (5%)
5 (5%)
10 (5%)
BORTEZOMIB
5 (5%)
5 (5%)
10 (5%)
CARFILZOMIB
5 (5%)
5 (5%)
10 (5%)
IXAZOMIB
5 (5%)
5 (5%)
10 (5%)
Chemotherapy
5 (5%)
5 (5%)
10 (5%)
Stem Cell Transplant
5 (5%)
5 (5%)
10 (5%)
Other
5 (5%)
5 (5%)
10 (5%)
HDAC Inhibitor
5 (5%)
5 (5%)
10 (5%)
Monoclonal Antibody
5 (5%)
5 (5%)
10 (5%)
CXCR4
5 (5%)
5 (5%)
10 (5%)
DARATUMUMAB
5 (5%)
5 (5%)
10 (5%)
ELOTUZUMAB
5 (5%)
5 (5%)
10 (5%)
SILTUXIMAB
5 (5%)
5 (5%)
10 (5%)
Engineered T Cell Therapy
5 (5%)
5 (5%)
10 (5%)
  Other
5 (5%)
5 (5%)
10 (5%)
Not Classified
5 (5%)
5 (5%)
10 (5%)
PPD


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248
Example: POP_T4
Protocol: BMA117159                                                                             Page 1 of 1
Population: Part 1    
(Data as of: 30MAY2001)     
Table x.xxxx
Summary of Multiple Myeloma Subjects Refractory to Prior Anti-Cancer Therapy by Drug Class of Agents (Part 1)
Drug Class
0.03 mg/kg
0.06 mg/kg
Total
(N=100)
(N=100)
(N=200)
Immunomodulator
5 (5%)
5 (5%)
10 (5%)
LENALIDOMIDE
5 (5%)
5 (5%)
10 (5%)
POMALIDOMIDE
5 (5%)
5 (5%)
10 (5%)
THALIDOMIDE
5 (5%)
5 (5%)
10 (5%)
Steroids
5 (5%)
5 (5%)
10 (5%)
Proteasome Inhibitor
5 (5%)
5 (5%)
10 (5%)
BORTEZOMIB
5 (5%)
5 (5%)
10 (5%)
CARFILZOMIB
5 (5%)
5 (5%)
10 (5%)
IXAZOMIB
5 (5%)
5 (5%)
10 (5%)
Chemotherapy
5 (5%)
5 (5%)
10 (5%)
Stem Cell Transplant
5 (5%)
5 (5%)
10 (5%)
Other
5 (5%)
5 (5%)
10 (5%)
Monoclonal Antibody
5 (5%)
5 (5%)
10 (5%)
CXCR4
5 (5%)
5 (5%)
10 (5%)
DARATUMUMAB
5 (5%)
5 (5%)
10 (5%)
ELOTUZUMAB
5 (5%)
5 (5%)
10 (5%)
SILTUXIMAB
5 (5%)
5 (5%)
10 (5%)
HDAC Inhibitor
5 (5%)
5 (5%)
10 (5%)
Not Classified
5 (5%)
5 (5%)
10 (5%)
Immunomodulator and Proteasome Inhibitor
5 (5%)
5 (5%)
10 (5%)
This table is summarized per subject level
PPD


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249
Example: POP_F2
Protocol: BMA117159                                                                               Page 1 of 1
Population: Part 2 MM                                                  (Data as of: 30MAY2001)
Figure x.xxxx
Plot of Dose Reduction of GSK28557916 by Cycle (Part 2 MM)
Doses 1.9 mg/kg and 1.7 mg/kg are combined and represented by 1.7 mg/kg.
PPD


CONFIDENTIAL
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250
Example: EFF_F1
Protocol: BMA117159                                                                               Page 1 of 1
Population: Part 2 MM
   (Data as of: 30MAY2001)
PPD
PPD


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251
Example: EFF_F2
Protocol: BMA117159                                                                               Page 1 of 1
Population: Part 2 MM
   (Data as of: 30MAY2001)
Figure x.xxxx
Forest Plot - Overall Response Rate (ORR) (Part 2 MM)
PPD


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252
Example: EFF_F3
Protocol: BMA117159                                                                               Page 1 of 1
Population: Part 2 MM
   (Data as of: 30MAY2001)
Figure x.xxxx
Profile Plot of Responders (Part 2 MM)
PPD


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253
Example: SAFE_T1
Protocol: BMA117159                                                                             Page 1 of 1
Population: Part 1    
(Data as of: 30MAY2001)
Table x.xxxx
Summary of Subjects Experiencing Corneal Clinical Signs (Part 1)
0.03 mg/kg
0.06 mg/kg
Total
(N=10)
(N=20)
(N=30)
Number of Subjects Experiencing Corneal Clinical Signs 
5 (50%)
15 (75%)
20 (67%)
Corneal Epithelium Finding
Abnormal, epithelial edema
5 (50%)
12 (60%)
17 (57%)
       Abnormal, epithelial edema -subtle epithelial haze
3 (30%)
11 (55%)
14 (47%)
       Abnormal, epithelial edema - diffuse microcystic changes
2 (20%)
8 (40%)
10 (33%)
       Abnormal, epithelial edema - mild patchy microcystic changes
1 (30%)
9 (45%)
10 (33%)
       ……
Abnormal, punctate keratopathy
4 (40%)
13 (65%)
17 (57%)
       Abnormal, punctate keratopathy - mild
3 (30%)
11 (55%)
14 (47%)
       Abnormal, punctate keratopathy - moderate
3 (30%)
10 (50%)
13 (43%)
       Abnormal, punctate keratopathy - severe
2 (20%)
7 (35%)
9 (30%)
       ……
Corneal Stroma Finding
Abnormal, active
4 (40%)
13 (65%)
17 (57%)
       Abnormal, active edema - trace
3 (30%)
11 (55%)
14 (47%)
       Abnormal, active edema - 1+
3 (30%)
10 (50%)
13 (43%)
       Abnormal, active edema - 2+
2 (20%)
7 (35%)
9 (30%)
       Abnormal, active opacity - mild
1 (10%)
6 (30%)
7 (23%)
       Abnormal, active opacity - moderate
1 (10%)
5 (25%)
6 (20%)
Number of Subjects Experiencing Corneal Clinical Signs at End of Study Treatment
5 (50%)
15 (75%)
20 (67%)
Corneal Epithelium Finding
Abnormal, epithelial edema
5 (50%)
12 (60%)
17 (57%)
       Abnormal, epithelial edema -subtle epithelial haze
3 (30%)
11 (55%)
14 (47%)
       Abnormal, epithelial edema - diffuse microcystic changes
2 (20%)
8 (40%)
10 (33%)
       Abnormal, epithelial edema - mild patchy microcystic changes
1 (30%)
9 (45%)
10 (33%)
       ……
Abnormal, punctate keratopathy
4 (40%)
13 (65%)
17 (57%)
       Abnormal, punctate keratopathy - mild
3 (30%)
11 (55%)
14 (47%)
       Abnormal, punctate keratopathy - moderate
3 (30%)
10 (50%)
13 (43%)
       Abnormal, punctate keratopathy - severe
2 (20%)
7 (35%)
9 (30%)
       ……


CONFIDENTIAL
BMA117159
254
Corneal Stroma Finding
Abnormal, active
4 (40%)
13 (65%)
17 (57%)
       Abnormal, active edema - trace
3 (30%)
11 (55%)
14 (47%)
       Abnormal, active edema - 1+
3 (30%)
10 (50%)
13 (43%)
       Abnormal, active edema - 2+
2 (20%)
7 (35%)
9 (30%)
       Abnormal, active opacity - mild
1 (10%)
6 (30%)
7 (23%)
       Abnormal, active opacity - moderate
1 (10%)
5 (25%)
6 (20%)
Number of Subjects Experiencing Corneal Clinical Signs at Last Follow-up Exam
5 (50%)
15 (75%)
20 (67%)
Corneal Epithelium Finding
Abnormal, epithelial edema
5 (50%)
12 (60%)
17 (57%)
       Abnormal, epithelial edema -subtle epithelial haze
3 (30%)
11 (55%)
14 (47%)
       Abnormal, epithelial edema - diffuse microcystic changes
2 (20%)
8 (40%)
10 (33%)
       Abnormal, epithelial edema - mild patchy microcystic changes
1 (30%)
9 (45%)
10 (33%)
       ……
Abnormal, punctate keratopathy
4 (40%)
13 (65%)
17 (57%)
       Abnormal, punctate keratopathy - mild
3 (30%)
11 (55%)
14 (47%)
       Abnormal, punctate keratopathy - moderate
3 (30%)
10 (50%)
13 (43%)
       Abnormal, punctate keratopathy - severe
2 (20%)
7 (35%)
9 (30%)
       ……
Corneal Stroma Finding
Abnormal, active
4 (40%)
13 (65%)
17 (57%)
       Abnormal, active edema - trace
3 (30%)
11 (55%)
14 (47%)
       Abnormal, active edema - 1+
3 (30%)
10 (50%)
13 (43%)
       Abnormal, active edema - 2+
2 (20%)
7 (35%)
9 (30%)
       Abnormal, active opacity - mild
1 (10%)
6 (30%)
7 (23%)
       Abnormal, active opacity - moderate
1 (10%)
5 (25%)
6 (20%)
       ……
Number of Subjects Experiencing Corneal Clinical Signs 
n
5
15
20
       Also reported corneal toxicity AE
3 (60%) 
9 (60%)
12 (60%)
       Did not report corneal toxicity AE
2 (40%)
6 (40%)
8 (60%)
PPD


CONFIDENTIAL
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255
Example: SAFE_T2
Protocol: BMA117159                                                                             Page 1 of 1
Population: Part 1    
(Data as of: 30MAY2001)   
Table x.xxxx
Summary of Best Corrected Visual Acuity Test Scores (logMAR score)(Part 1)
0.03 mg/kg 0.06 mg/kg Total
Timepoint
Eye
BCVA Score
(N=xx)
(N=xx)
(N=xx)
Baseline
Right n
Xx
Xx
xxx
Mean
x.xx
x.xx
x.xx
SD
x.xxx
x.xxx
x.xxx
Median
x.xx
x.xx
x.xx
Min
x
x
x
Max
x
x
x
Left
n
Xx
Xx
xxx
Mean
x.xx
x.xx
x.xx
SD
x.xxx
x.xxx
x.xxx
Median
x.xx
x.xx
x.xx
Min
x
x
x
Max
x
x
x
End of study treatment
Right n
Xx
Xx
xxx
Mean
x.xx
x.xx
x.xx
SD
x.xxx
x.xxx
x.xxx
Median
x.xx
x.xx
x.xx
Min
x
x
x
Max
x
x
x
Left
n
Xx
Xx
xxx
Mean
x.xx
x.xx
x.xx
SD
x.xxx
x.xxx
x.xxx
Median
x.xx
x.xx
x.xx
Min
x
x
x
Max
x
x
x
Change from baseline to 
Right n
xx
xx
xx


CONFIDENTIAL
BMA117159
256
end of study treatment
No change/improved vision
xx (xx%)
xx (xx%)
xx (xx%)
Possible worsened vision
xx (xx%)
xx (xx%)
xx (xx%)
Definite worsened vision
xx (xx%)
xx (xx%)
xx (xx%)
Left
n
xx
xx
xx
No change/improved vision
xx (xx%)
xx (xx%)
xx (xx%)
Possible worsened vision
xx (xx%)
xx (xx%)
xx (xx%)
Definite worsened vision
xx (xx%)
xx (xx%)
xx (xx%)
Last follow-up exam
Right n
Xx
Xx
xxx
Mean
x.xx
x.xx
x.xx
SD
x.xxx
x.xxx
x.xxx
Median
x.xx
x.xx
x.xx
Min
x
x
x
Max
x
x
x
Left
n
Xx
Xx
xxx
Mean
x.xx
x.xx
x.xx
SD
x.xxx
x.xxx
x.xxx
Median
x.xx
x.xx
x.xx
Min
x
x
x
Max
x
x
x
Change from baseline to 
Right n
xx
xx
xx
last follow-up exam
No change/improved vision
xx (xx%)
xx (xx%)
xx (xx%)
Possible worsened vision
xx (xx%)
xx (xx%)
xx (xx%)
Definite worsened vision
xx (xx%)
xx (xx%)
xx (xx%)
Left
n
xx
xx
xx
No change/improved vision
xx (xx%)
xx (xx%)
xx (xx%)
Possible worsened vision
xx (xx%)
xx (xx%)
xx (xx%)
Definite worsened vision
xx (xx%)
xx (xx%)
xx (xx%)
Maximum (worst) change 
from baseline
Right n
xx
xx
xx
No change/improved vision
xx (xx%)
xx (xx%)
xx (xx%)
Possible worsened vision
xx (xx%)
xx (xx%)
xx (xx%)
Definite worsened vision
xx (xx%)
xx (xx%)
xx (xx%)


CONFIDENTIAL
BMA117159
257
Left
N
xx
xx
xx
No change/improved vision
xx (xx%)
xx (xx%)
xx (xx%)
Possible worsened vision
xx (xx%)
xx (xx%)
xx (xx%)
Definite worsened vision
xx (xx%)
xx (xx%)
xx (xx%)
Note: High scores are associated with worse vision, and low scores with better vision. No change/improved 
vision is defined as a change from baseline <0.12; a possible worsened vision is defined as a change from 
baseline >=0.12 to <0.3; a definite worsened vision is defined as a change from baseline >=0.3 logMAR score. 
For “End of study Treatment”, summarize for subjects with ocular exam results at the end of study treatment; 
ocular assessment For “Change from baseline to end of study treatment”, summarize for subjects with ocular 
exam results at baseline and the end of study treatment. For “Maximum (worst) change from baseline”, summarize 
for subjects with ocular exam results at baseline and at least one post-baseline visit.
Subjects with “worse than 20/400” results will not be included in the summary.
PPD


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258
Example: SAFE_T3
Protocol: BMA117159                                                                             Page 1 of 1
Population: Part 1    
(Data as of: 30MAY2001)   
Table x.xxxx
Summary of Symptom Impact and HRQoL Item Scores Part 1)
Item Score=Bone Pain Worst
Treatment: 0.03 mg/kg (N=200)
Planned Time
n
Mean
  SD
Median
Min.
Max.
Baseline
Score
xx
xx.x
xx.xx
xx
xx
xx
Cycle 1 Day 1 to Day 8 Average Score
xx xx.x 
xx.xx xx
xx  xx 
Change from Baseline
xx xx.x 
xx.xx xx
xx  xx 
Cycle 1 Day 15    
Score
xx xx.x 
xx.xx xx
xx  xx 
Change from baseline
xx xx.x 
xx.xx xx
xx  xx 
Note: This mock up will be used for both summary of item scores and change from baseline. For summary of 
change from baseline, include baseline scores. Include Bone Pain Worst, Bone Pain Average, Fatigue worst in 
one summary table. This note dose not need to be included in the final output. Will add the notes to 
programming notes
PPD


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259
Example: SAFE_T4
Protocol: BMA117159                                                                             Page 1 of 1
Population: Part 1    
(Data as of: 30MAY2001)   
Table X.XXXX
Summary of Human Anti-GSK2857916 Antibodies (ADA) Over Time
Visit 
   Category 
Cohort 1 (x mg/kg) 
   Results 
    (N=X)
-----------------------------------------------------------------------------------------------
CYCLE 1 WEEK 1
  Screening ADA Result
    n                   X 
    POSITIVE 
      X (X%)
    NEGATIVE            X (X%) 
  Confirming ADA Result
    n 
X 
    POSITIVE            X 
    NEGATIVE            X (X%)
  
  Conclusive
    n                   X 
    NEGATIVE,CONCLUSIVE X (X%) 
Note: Negative, Conclusive is a Negative result in ADA assay (either negative screening or negative confirming 
assay result) and GSK2857916 total antibody concentration <=25000 ng/mL in pharmacokinetic sample collected at 
same time or same day prior to dosing as the ADA sample. Negative ADA results, either negative screening or 
negative confirming assay results, are not considered conclusive when the GSK2857916 total antibody 
concentration was >25000 ng/mL or no GSK2857916 total antibody concentration was available at same time or 
same day prior to dosing as the ADA sample.
PPD


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260
Example: SAFE_T5
Protocol: BMA117159                                                                             Page 1 of 1
Population: Part 1    
(Data as of: 30MAY2001)   
Table x.xxxx
Summary of Anti-GSK2857916 Antibodies (ADA)
  X mg/kg
   (N=X)
-----------------------------------------------------------------------------------------------------------
Number of subjects with baseline ADA results  
         
  n                                                                                          X
  Number of subjects with negative baseline ADA results                                      X (X%)
  Number of subjects with confirmed positive baseline ADA results 
         X (X%)
Number of subjects with post-baseline ADA results                                            X 
  n                                                                                          X
  Number of subjects with at least one confirmed positive post-baseline ADA result           X (X%)
  
  Number of subjects with all negative post-baseline ADA results and
  at least one GSK2857916 total antibody concentration 25000 ng/mL 
   X (X%)
  Number of subjects with all negative post-baseline ADA results and 
  all GSK2857916 total antibody concentration >25000 ng/mL or missing
   X (X%)
  
Note a subject is considered to have a positive ADA result if they have a positive screening assay,
a positive confirmation assay and a titer value. A baseline ADA result is the closest ADA sample (i.e. either 
Screening Visit or Cycle 1 Day 1 Visit) prior to the subject receiving the first dose of GSK2857916.
PPD


CONFIDENTIAL
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261
Example: SAFE_F1
Protocol: BMA117159                                                                               Page 1 of 1
Population: Part 1            
   (Data as of: 30MAY2001)
Figure x.xxxx
Proportions of Subjects with Infusion-related Reactions (Part 1)
PPD


CONFIDENTIAL
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262
Example: SAFE_F2
Protocol: BMA117159                                                                               Page 1 of 1
Population: All Treated MM            
   (Data as of: 30MAY2001)
Figure x.xxxx
Profile plot for patients with No Corneal Event or Grade 1 Corneal Event (Part 2 MM)
PPD


CONFIDENTIAL
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263
Example SAFE_L1
Protocol: BMA117159                                                                             Page 1 of 1
Population: Part 2 MM                                                               (Data as of: 30MAY2003)
                                              Listing x.xxxx
    Listing of Disease Characteristics, Prior Treatment, Dose Modification and Response to GSK2857916
                                                (Part 2 MM)
Part: 2
Treatment: 3.40 MM
                                                                        Refractory
                                             Refractory                 to both
                              Number of      to Last                    Immunomodulators and
  Centre ID/    ISS Stage at  Prior Lines    line of      Prior         Proteasome    Best Confirmed
  Subj.         Screening     of Therapy     Therapy      Daratumumab?  Inhibitors?   Response
  --------------------------------------------------------------------------------------------------------
 
       III           6 Lines        Yes          Yes           Yes           Progressive disease
 
 
       II            7 Lines        Yes                        Yes           Very Good Partial
 
                                                                             Response (VGPR)
 
       I             8 Lines        Yes                        Yes           Very Good Partial
 
                                                                             Response (VGPR)
PPD
PPD


CONFIDENTIAL
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Example SAFE_L2
Protocol: BMA117159                                                                             Page 1 of 1
Population: All Treated MM                                                           (Data as of: 30MAY2003)
Listing x.xxxx
Listing of Visual Acuity and Abnormal Corneal Exam Results
Part 1
Treatment: 0.01 mg/kg
Centre/
Subj.
Age(y)/
Sex/
Race
Experienced 
Corneal 
Clinical 
Signs / 
Reported 
Corneal 
Toxicity AE
Cycle/Visi
t
Time 
Since 1st 
Dose / 
Time 
Since 
Last Dose  Eye
Visual Acuity 
Corneal Exam Test/Result/ 
Represent a Corneal Clinical 
Sign
65/
F/
White -
White/Cauca
sian/Europe
an Heritage 
Y / Y
3 / DAY 1
43d / 1d
R
20/40
Corneal epithelium / Abnormal, 
punctate keratopathy – mild / Y
L
20/60
Corneal epithelium / Abnormal, 
punctate keratopathy – mild / Y
4 / DAY 1
64d / 1d 
R
20/40
Corneal endothelium / Abnormal, 
guttata / N
L
20/40
Corneal endothelium / Abnormal, 
guttata / N
5 / DAY 1
85d / 1d 
R
20/25
Corneal epithelium / Abnormal, 
epithelial edema - mild patchy 
microcystic changes / Y
L
20/40
Corneal epithelium / Abnormal, 
epithelial edema - mild patchy 
microcystic changes / Y
PPD
PPD


CONFIDENTIAL
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Example: SAFE_L3
Protocol: BMA117159                                                                               Page 1 of 1
Population: All Treated MM            
   (Data as of: 30MAY2001)
Listing x.xxxx
Listing of Anti-GSK2857916 antibody results (All Treated MM)
Treatment: X
            
                                         GSK2857916        GSK2857916
            Age (y)
                                         Concentration     Concentration
Centre ID/  Sex                     Study                Screening     Confirming            (ADC)            (Total mAb)
Subj.       Race    Visit           Date        Day      Assay         Assay        Titer    (ng/mL)           (ng/mL)
------------------------------------------------------------------------------------------------------------------------------------------
XXXX/ 
    X
   CYCLE X WEEK X  DDMMMYYYY    X        X            X            X         X                x
X           X
    X
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Example: PK_T1
Protocol: BMA117159                                                                               Page 1 of 1
Population: PK                         
   (Data as of: 30MAY2001)
                                                Table xx.xxx
Summary of Results of Dose Proportionality Analysis for ADC PK Parameters (AUC(0-inf), AUC(0-t), Cmax, and
AUC(0-τ)) Using Power Model
                                                           Standard
Parameter             Doses        Adjusted mean slope       error    DF          90% C.I.
---------------------------------------------------------------------------------------------------------
AUCIFO                0.03 mg/kg
0.98                 0.036      17        (0.92, 1.05)
(ng*hr/mL)
0.06 mg/kg
0.97
0.034
   17
     (0.93, 1.06)
………
AUCLST                0.03 mg/kg 
0.99                 0.037      17        (0.92, 1.05)
(ng*hr/mL)
0.06 mg/kg 
0.99                 0.037      17        (0.92, 1.05)
………
CMAX                  0.03 mg/kg 
0.92                 0.057      17        (0.82, 1.01)
(ng/mL)
0.06 mg/kg 
0.92                 0.057      17        (0.82, 1.01)
…………
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Example: PK_F1
Protocol: BMA117159                                                                               Page 1 of 1
Population: PK                         
   (Data as of: 30MAY2001)
Figure x.xxxx
Plot of Geometric Mean and 95%CI of Analyte Ratios for GSK2857916 Analytes by cycle (Linear and Semi-Log) 
(Part 1)
Treatment: X


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Example: PK_F2
Protocol: BMA117159                                                                               Page 1 of 1
Population: PK                         
   (Data as of: 30MAY2001)
Figure x.xxxx
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CONFIDENTIAL
The GlaxoSmithKline group of companies
BMA117159
1
Division
:
Worldwide Development
Information Type
:
Reporting and Analysis Plan (RAP)
Title
:
DREAMM-1: A Phase I Open-label, Dose Escalation Study 
to Investigate the Safety, Pharmacokinetics, 
Pharmacodynamics, Immunogenicity and Clinical Activity of 
the Antibody Drug Conjugate GSK2857916 in Subjects with 
Relapsed/Refractory Multiple Myeloma and Other Advanced 
Hematologic Malignancies Expressing BCMA
Compound Number 
:
GSK2857916
Effective Date 
:
26-JUN-2018
Description:

The purpose of this RAP is to describe the planned analyses and output to be 
included in the Clinical Study Report for Protocol GSK Document Number 
2012N155299_05.

This RAP is intended to describe the safety, clinical activity and pharmacokinetic
analyses required for the study. 

This RAP will be provided to the study team members to convey the content of the 
Statistical Analysis Complete (SAC) deliverable.
RAP Author(s):
Approver
Date
Approval Method
25-JUN-2018
E-mail
Principal Statistician (Oncology, Clinical 
Statistics)
Data Analyst Statistician (Oncology, Clinical 
Statistics)
22-JUN-2018
E-mail
25-JUN-2018
E-mail
Director (Clinical Pharmacology Modelling & 
Simulation)
Copyright 2018 the GlaxoSmithKline group of companies. All rights reserved.  
Unauthorised copying or use of this information is prohibited.
PPD
PPD
PPD


CONFIDENTIAL
BMA117159
2
RAP Team Approvals:
Approver
Date
Approval Method
 (PPL and Medical Monitor)
22-JUN-2018
E-mail
Director Clinical Development (Oncology, ES 
Clinical)
 (CRL)
22-JUN-2018
E-mail
Clinical Development Director (Oncology, 
CPSSO)
(CIL)
22-JUN-2018
E-mail
Clinical Development Director (Oncology, 
Therapy Area Delivery CPSSO Management)
(OSL)
22-JUN-2018
E-mail
Clinical Development Manager (Oncology, 
Therapy Area Delivery CPSSO Management)
 (Global Regulatory Lead)
22-JUN-2018
E-mail
Senior Director (Oncology Therapeutic Group, 
Global Regulatory Affairs)
 (SDL)
22-JUN-2018
E-mail
Safety Development Leader (Pharmacovigilance, 
GCSP)
22-JUN-2018
E-mail
SERM Director (Pharmacovigilance, GCSP)
20-JUN-2018
E-mail
VEO Director (Oncology Value Evidence and 
Outcomes, Value Evidence & Outcomes)
20-JUN-2018
E-mail
Director (Patient Reported Outcomes)
22-JUN-2018
E-mail
Director, Statistics (Oncology, Clinical Statistics)
22-JUN-2018
E-mail
Manager Data Management (Oncology, CPSSO 
Data Management)
22-JUN-2018
E-mail
Programming Manager (Oncology, Clinical 
Programming)
26-JUN-2018
E-mail
Head of Medical Writing (Oncology, ES 
Clinical)
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


CONFIDENTIAL
BMA117159
3
Approver
Date
Approval Method
21-JUN-2018
E-mail
Scientific Leader (Immunogenicity and Clinical 
Immunology, In vitro / In vivo Translation)
Clinical Statistics and Clinical Programming Line Approvals:
Approver
Date
Approval Method
21-JUN-2018
E-mail
Senior Statistics Director (Oncology, Clinical 
Statistics)
21-JUN-2018
E-mail
Director Programming (Oncology, Clinical 
Programming)
PPD
PPD
PPD


CONFIDENTIAL
BMA117159
4
TABLE OF CONTENTS
PAGE
1.
INTRODUCTION......................................................................................................8
2.
SUMMARY OF KEY PROTOCOL INFORMATION ..................................................9
2.1.
Changes to the Protocol Defined Statistical Analysis Plan............................9
2.2.
Study Objective(s) and Endpoint(s).............................................................10
2.3.
Study Design ..............................................................................................12
2.4.
Statistical Hypotheses / Statistical Analyses ...............................................13
3.
PLANNED ANALYSES ..........................................................................................14
3.1.
Interim Analyses .........................................................................................14
3.1.1.
Part 1: Dose Escalation Phase ....................................................14
3.1.1.1.
Description of the New Continual 
Reassessment Method...............................................14
3.1.1.2.
Prior Probability Distribution .......................................15
3.1.1.3.
Displays To Be Created For Dose Escalation 
Review .......................................................................16
3.1.2.
Part 2 Expansion Phase ..............................................................16
3.1.2.1.
Multiple Myeloma Expansion Cohort ..........................16
3.1.2.1.1.
Operating Characteristics of the 
Stopping Rules for Futility.......................17
3.1.2.2.
Lymphoma Expansion Cohort ....................................17
3.2.
Administrative Interim Analyses ..................................................................18
3.3.
Final Analyses ............................................................................................18
4.
ANALYSIS POPULATIONS ...................................................................................19
4.1.
Protocol Deviations.....................................................................................20
5.
CONSIDERATIONS FOR DATA ANALYSES AND DATA HANDLING 
CONVENTIONS.....................................................................................................21
5.1.
Study Treatment & Sub-group Display Descriptors.....................................21
5.2.
Baseline Definitions ....................................................................................21
5.2.1.
Examination of Subgroups...........................................................22
5.3.
Other Considerations for Data Analyses and Data Handling 
Conventions................................................................................................23
6.
STUDY POPULATION ANALYSES .......................................................................24
6.1.
Overview of Planned Study Population Analyses........................................24
6.2.
Disposition of Subjects................................................................................24
6.3.
Demographic and Baseline Characteristics.................................................24
6.4.
Treatment Compliance................................................................................25
6.5.
Extent of Exposure .....................................................................................25
6.6.
Concomitant Medications............................................................................26
6.7.
Subsequent Anti-Cancer Therapies ............................................................27
7.
EFFICACY ANALYSES..........................................................................................28
7.1.
Primary Efficacy Analyses ..........................................................................28
7.2.
Secondary Efficacy Analyses......................................................................28
7.2.1.
Multiple Myeloma.........................................................................28


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BMA117159
5
7.2.1.1.
Endpoint / Variables ...................................................28
7.2.1.1.1.
Overall Response Rate...........................28
7.2.1.1.2.
Response Confirmation Algorithm ..........28
7.2.1.2.
Summary Measure .....................................................32
7.2.1.3.
Population of Interest..................................................32
7.2.2.
Lymphoma...................................................................................32
7.2.2.1.
Endpoint / Variables ...................................................32
7.2.2.1.1.
Overall Response Rate...........................32
7.2.2.2.
Summary Measure .....................................................32
7.2.2.3.
Population of Interest..................................................32
7.2.3.
Strategy for Intercurrent (Post-Randomization) Events ................32
7.2.4.
Statistical Analyses / Methods .....................................................33
7.3.
Exploratory Efficacy Analyses.....................................................................33
7.3.1.
Multiple Myeloma.........................................................................33
7.3.1.1.
Endpoint / Variables ...................................................33
7.3.1.2.
Summary Measure .....................................................33
7.3.1.2.1.
Progression-Free Survival ......................33
7.3.1.2.2.
Time to Progression................................36
7.3.1.2.3.
Duration of Response.............................37
7.3.1.2.4.
Time to Response ..................................37
7.3.1.2.5.
Time to Best Response ..........................37
7.3.1.2.6.
Overall Survival ......................................38
7.3.1.3.
Monoclonal Protein and Serum Free Light 
Chain..........................................................................38
7.3.1.4.
Subgroup Analysis of ORR.........................................39
7.3.1.5.
Population of Interest..................................................39
7.3.2.
Strategy for Intercurrent (Post-Randomization) Events ................39
7.3.3.
Statistical Analyses / Methods .....................................................39
8.
SAFETY ANALYSES .............................................................................................40
8.1.
Adverse Events Analyses ...........................................................................40
8.2.
Adverse Events of Interest Analyses...........................................................41
8.3.
Deaths and Serious Adverse Events...........................................................42
8.4.
Adverse Events Leading to Discontinuation of Study Treatment 
and/or Withdrawal from the Study and Other Significant Adverse 
Events ........................................................................................................43
8.5.
Pregnancies................................................................................................43
8.6.
Clinical Laboratory Analyses.......................................................................43
8.6.1.
Analyses of Liver Function Tests .................................................44
8.7.
Other Safety Analyses ................................................................................44
9.
PHARMACOKINETIC ANALYSES.........................................................................47
9.1.
Endpoint / Variables....................................................................................47
9.1.1.
Drug Concentration Measures .....................................................47
9.1.2.
Derived Pharmacokinetic Parameters..........................................47
9.1.2.1.
Non-compartmental Analysis......................................47
9.2.
Population of Interest..................................................................................48
9.3.
Statistical Analyses / Methods ....................................................................48
9.3.1.
Statistical Methodology Specification...........................................48
9.3.1.1.
Exploratory assessment of dose 
proportionality:............................................................48
9.3.1.2.
Assessment of Accumulation Ratio: ...........................49


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BMA117159
6
9.3.1.3.
Assessment of Analyte Ratios: ...................................50
9.3.2.
Model Checking & Diagnostics ....................................................52
10. POPULATION PHARMACOKINETIC (POPPK) ANALYSES..................................53
11. PHARMACODYNAMIC (AND / OR BIOMARKER) ANALYSES .............................54
12. PHARMACOKINETIC / PHARMACODYNAMIC ANALYSES .................................55
12.1.
Exposure-Response for Efficacy and Corneal Events.................................55
12.2.
Concentration-QTc Analyses ......................................................................55
13. HEALTH OUTCOMES ANALYSES........................................................................56
14. ANTI-DRUG ANTIBODY ANALYSES.....................................................................57
15. REFERENCES.......................................................................................................58
16. APPENDICES........................................................................................................59
16.1.
Appendix 1: Protocol Deviation Management and Definitions for Per 
Protocol Population.....................................................................................59
16.2.
Appendix 2: Schedule of Activities ..............................................................60
16.2.1.
Protocol Defined Schedule of Events...........................................60
16.2.2.
Dose Escalation...........................................................................61
16.2.2.1.
Every 3 Weeks Dosing Schedule for Multiple 
Myeloma.....................................................................61
16.2.2.2.
Weekly Dosing Schedule (Dose Escalation) for 
Multiple Myeloma .......................................................65
16.2.3.
Dose Expansion...........................................................................69
16.2.3.1.
Every 3 Weeks Dosing Schedule for Multiple 
Myeloma.....................................................................69
16.2.3.2.
Dose Expansion Weekly Dosing Schedule for 
Multiple Myeloma .......................................................74
16.2.3.3.
Dose Expansion Every 3 Weeks Dosing 
Schedule for Lymphomas...........................................78
16.2.3.4.
Dose Expansion Weekly Dosing Schedule for 
Lymphomas................................................................82
16.3.
Appendix 3: Assessment Windows .............................................................85
16.4.
Appendix 4: Study Phases and Treatment Emergent Adverse 
Events ........................................................................................................86
16.4.1.
Study Phases ..............................................................................86
16.4.1.1.
Study Time Periods for Concomitant 
Medications and Blood and Blood Supportive 
Care Products ............................................................86
16.4.2.
Treatment Emergent Flag for Adverse Events .............................87
16.5.
Appendix 5: Data Display Standards & Handling Conventions....................88
16.5.1.
Reporting Process .......................................................................88
16.5.2.
Reporting Standards....................................................................88
16.5.3.
Reporting Standards for Pharmacokinetic....................................89
16.5.4.
Extended Loss to Follow-up or Extended Time without an 
Adequate Assessment.................................................................90
16.5.5.
Date Associated with Response ..................................................90
16.6.
Appendix 6: Derived and Transformed Data ...............................................91
16.6.1.
General........................................................................................91


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BMA117159
7
16.6.2.
Study Population..........................................................................91
16.6.3.
Efficacy........................................................................................91
16.6.4.
Safety ..........................................................................................92
16.7.
Appendix 7: Reporting Standards for Missing Data.....................................93
16.7.1.
Premature Withdrawals................................................................93
16.7.2.
Handling of Missing Data.............................................................93
16.7.2.1.
Handling of Missing and Partial Dates ........................94
16.8.
Appendix 8: Values of Potential Clinical Importance ...................................96
16.8.1.
Laboratory Parameters ................................................................96
16.8.2.
ECG Parameters and vital signs..................................................96
16.9.
Appendix 9: Population Pharmacokinetic (PopPK) Analyses ......................97
16.9.1.
Population Pharmacokinetic (PopPK) Dataset 
Specification ................................................................................97
16.9.2.
Population Pharmacokinetic (PopPK) Methodology...................107
16.10. Appendix 10: Pharmacokinetic / Pharmacodynamic Analyses ..................110
16.10.1. Pharmacokinetic / Pharmacodynamic Dataset 
Specification ..............................................................................110
16.10.2. Pharmacokinetic / Pharmacodynamic Methodology...................117
16.10.2.1. PD Model of sBCMA Binding....................................117
16.10.2.2. Exposure-Response Analyses..................................118
16.10.2.2.1. Corneal Toxicity....................................118
16.10.2.2.2. Clinical Response.................................118
16.11. Appendix 11: Abbreviations & Trade Marks ..............................................119
16.11.1. Abbreviations.............................................................................119
16.11.2. Trademarks ...............................................................................121
16.12. Appendix 12: List of Data Displays............................................................122
16.12.1. Data Display Numbering............................................................122
16.12.2. Mock Example Shell Referencing ..............................................122
16.12.3. Deliverables...............................................................................122
16.12.4. Study Population Tables............................................................123
16.12.5. Study Population Figures...........................................................141
16.12.6. Efficacy Tables ..........................................................................142
16.12.7. Efficacy Figures .........................................................................151
16.12.8. Safety Tables.............................................................................154
16.12.9. Safety Figures ...........................................................................193
16.12.10.Pharmacokinetic Tables.............................................................196
16.12.11.Pharmacokinetic Figures ...........................................................204
16.12.12.Pharmacokinetic / Pharmacodynamic (and / or Biomarker) 
Figures ......................................................................................210
16.12.13.ICH Listings ...............................................................................211
16.12.14.Non-ICH Listings........................................................................226
16.13. Appendix 13: Example Mock Shells for Data Displays ..............................238


CONFIDENTIAL
BMA117159
8
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:
Revision Chronology:
2012N155299_00
2013-DEC-26
Original
2012N155299_01
2014-MAR-01
Amendment No. 1. Country specific Amendment for the 
United Kingdom to address required changes per MHRA.  
Updated Exclusion Criteria to exclude subjects with current 
corneal disease or history of corneal disease.  Updated 
QTc withdrawal criterion to modify QTc withdrawal for QTc 
>500msec and to include > 60 msec increase from 
baseline.  Updated Data Management Section 12 to 
include details on dissemination of data and 
communication plan.  
2012N155299_02
2014-MAR-20
Amendment No. 2. Global Amendment to address required 
changes per the FDA.  Updated Inclusion Criteria with 
minimum weight requirement.  Updated Blood Volumes.  
Revised Time and Events Tables. Corrected typographical 
errors.
2012N155299_03
2014-MAY-05
Amendment No. 3. Country specific Amendment for 
Canada to address required changes per Health Canada.  
Updated preparation instructions of GSK2857916.
2012N155299_04
2016-MAY-05
Amendment No. 4. Global Amendment to include patient 
reported outcome instruments in the Part 2 multiple 
myeloma cohort and refine the lymphoma histologies 
eligible in Part 2 BCMA-expressing lymphoma cohort. 
Additionally, the requirement for 60% of tumor cells 
staining positive for BCMA expression was removed. The 
total number of subjects that may be enrolled is presented 
by a range of 80 to 95 to provide an updated estimate 
based on the number of subjects who enrolled at the time 
of the amendment.  Additional modifications include: 
changing the time-point specific blood specimens are 
collected for baseline/pre-treatment immunogenicity and 
biomarker measurements, and the visit window for certain 
assessments.
2012N155299_05
2017-NOV-02
Global amendment to include additional follow up of 
multiple myeloma subjects for ocular exams (for those 
whose corneal signs or symptoms have not resolved), 
additional patient reported outcome instruments, addition of 
time-to-event endpoints as exploratory objectives. Subjects 
who have completed treatment or the 3 month follow up 
visit (end of study) prior to amendment 5 will be 
reconsented for further follow up and survival status. Other 
administrative changes are also included


CONFIDENTIAL
BMA117159
9
2.
SUMMARY OF KEY PROTOCOL INFORMATION
2.1.
Changes to the Protocol Defined Statistical Analysis Plan
Changes from the originally planned statistical analysis specified in the protocol are 
outlined in Table 1.
Table 1
Changes to Protocol Defined Analysis Plan
Protocol
Reporting & Analysis Plan
Statistical Analysis Plan
Statistical Analysis Plan
Rationale for Changes

Time to response (TTR) is 
defined as the time between the 
date of first dose and the first 
documented evidence of 
response (PR or better). 
Subjects without confirmed 
response (PR or better) will be 
censored at the censoring date 
for TTP.

Time to response (TTR) is 
defined as the time 
between the date of first 
dose and the first 
documented evidence of 
response (PR or better), 
among subjects who 
achieve a response (i.e., 
confirmed PR or better).

To be consistent with GSK
Integrated Data Standards 
Library (IDSL) standard

Time to best response (TTBR) 
analyses was not planned.

Time to best response 
(TTBR), defined as the time 
between the date of first 
dose and the best response 
(PR or better), among 
subjects who achieve a 
response (i.e., confirmed 
PR or better), was added as 
an exploratory endpoint.

To further evaluate clinical 
activity of GSK2857916.

The ‘Pharmacokinetic (PK) 
Population’ is defined as those 
subjects in the “All Treated” 
population from whom at least 
one PK sample was obtained, 
analyzed, and was measurable.

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).

To be consistent with the 
latest GSK (IDSL) standard.

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

Descriptive statistics (mean, 
standard deviation, median, 
range) will be used to 
summarize change from 
baseline in observed value 
at each scheduled visit, as 
appropriate

To be consistent with the 
latest GSK (IDSL) standard.


CONFIDENTIAL
BMA117159
10
2.2.
Study Objective(s) and Endpoint(s)
Objectives
Endpoints
Primary Objectives
Primary Endpoints

To determine safety, tolerability, 
maximum tolerated dose (MTD), and 
recommended phase (RP2) dose and 
schedule of GSK2857916 
administered

Adverse events (AE) and changes in clinical signs and 
laboratory parameters
Secondary Objectives
Secondary Endpoints

To evaluate the pharmacokinetic (PK) 
profile of GSK2857916 and the 
breakdown product cys-mcMMAF
after intravenous (IV) single and 
repeat dose administration in subjects 
with relapsed/refractory MM and 
BCMA expressing lymphomas

GSK2857916 and cys-mcMMAF PK parameters following 
IV single and repeat dose administration during dose 
escalation as data permit (e.g., AUCs Cmax, tmax, CL, 
VSS, t½ [single dose], Cmax and Ctrough [repeat dose]).
GSK2857916 population PK parameters in expansion 
cohorts at the RP2 dose (e.g. clearance (CL), volume of 
distribution (Vd)), and relevant covariates which may 
influence exposure (e.g. age, weight, or disease-related 
covariates e.g. BCMA expression) 

To assess anti-drug antibody (ADA) 
formation after IV single and repeat 
dose administration of GSK2857916

ADA incidence and titers after single and repeat IV dosing 
of GSK2857916

To explore the initial anti-tumor activity 
of GSK2857916 in subjects with 
relapsed/refractory MM and BCMA 
expressing lymphomas

Clinical activity measured as Overall Response Rate 
(ORR) which is defined as follows:
o
For MM: the percentage of subjects achieving 
confirmed partial response or better (PR) 
o
In addition, the percentage of subjects with minimal 
response (MR) will be assessed for clinical benefit 
rate (CBR) (Appendix 1 of protocol)

For Lymphomas: the percentage of subjects achieving 
PR or better (PR) (Appendix 2 of protocol)
Exploratory Objectives
Exploratory Endpoints

To evaluate PD markers in MM after 
treatment with GSK2857916

sBCMA levels, BCMA receptor occupancy and cell death 
markers in subjects with MM. 

To explore relationships of 
GSK2857916 plasma 
concentrations/exposure with 
pharmacodynamics (PD), safety and 
clinical activity 

Relationship between receptor occupancy, tumor cell 
death markers, sBCMA and GSK2857916 plasma PK 
parameters;

Relationship between safety/clinical activity (e.g. ORR) 
and GSK2857916 PK parameters 

To characterize the relationship 
between clinical response and other 
biologic tumor characteristics (DNA, 
protein analysis)

BCMA expression levels on malignant cells as measured 
by IHC and/or flow cytometry in tumor tissue, serum 
sBCMA levels and their relationship to clinical response

To investigate the relationship 
between genetic variants in the host 
and response to study medicine, or 
susceptibility, severity and 
progression of disease 

Relationship between host genetic variation and response 
to study medicine or susceptibility, severity and 
progression of disease


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BMA117159
11
Objectives
Endpoints

To explore the effect of GSK2857916 
on symptoms (including bone pain, 
fatigue and visual symptoms) and 
impacts on HRQoL in subjects with 
relapsed/refractory MM (Part 2)

Changes from baseline in bone pain/fatigue and 
analgesic use as measured by the eDiary

Interviews with subjects to further characterize changes in 
symptoms (including bone pain/, fatigue and visual 
symptoms) and impacts on HRQoL

To explore changes in visual 
symptoms and function following 
discontinuation of treatment with 
GSK2857916

Changes in visual symptoms and impacts as measured 
by the OSDI and NEI-VFQ-25 following treatment 
discontinuation

Follow-up telephone interviews conducted to further 
understand subjects experience with visual symptoms 
and changes in symptoms and related impacts following 
treatment discontinuation

To explore the initial anti-tumor 
activity of GSK2857916 in subjects 
with relapsed/refractory MM in terms 
of time-to-event (TTE) endpoints (Part 
2 MM)

Time to progression (TTP), defined as: the time from 
first dose until the earliest date of PD per International 
Multiple Myeloma Working Group (IMWG), or death due 
to PD.

Duration of response (DOR), defined as: the time from 
first documented evidence of PR or better; until the time 
when disease progression (PD) is documented per 
IMWG; or death due to PD occurs in subjects who 
achieve a response, i.e. confirmed PR or better.

Time to response (TTR), defined as: the time between 
the date of first dose and the first documented evidence 
of response (PR or better), among subjects who achieve 
a response, i.e. confirmed PR or better. 

Time to best response (TTBR), defined as the time 
between the date of first dose and first documented 
evidence of the best response (PR or better), among 
subjects who achieve a response (i.e., confirmed PR or 
better).

Progression-free survival (PFS), defined as: the time 
from first dose until the earliest date of disease 
progression (PD) per IMWG, or death due to any cause.

Number of deaths.


CONFIDENTIAL
BMA117159
12
2.3.
Study Design
Overview of Study Design and Key Features
MTD1
4
3
1
2
25% of MTD1/RP2D1
MTD2/RP2D2
BCMA-positive Lymphomas (n =≈10)
Multiple myeloma  (n ≈ 40)
PART 1: Dose Escalation
(n≈30)
PART 2: Expansion Cohorts 
(n≈50)
2
3
1
*Cohort size to increase, n≈3 if ≥Grade 2 
drug related toxicity reported
5-9
4
RP2D1
Design
Features

Part 1 Dose Escalation 
o
Population: Subjects with relapsed/refractory MM (originally planned to enrol up 
to 30 subjects. However, additional subjects were enrolled to explore a new 
intermediate dose group)
o
Objective: characterize safety, PK, PD, immunogenicity and establish RP2 dose 
of GSK2857916
o
Two dosing schedules (Schedule 1 and Schedule 2) may be explored:

Schedule 1: GSK2587916 once every 3 weeks (21-day cycle) (n=~20)

Schedule 2: GSK2587916 once weekly for 3 consecutive weeks, 1-week rest 
(28-day cycle) (n=~9). Schedule 2 was not actually explored.
o
Serial PK samples will be collected from all subjects in Part 1

Part 2 Expansion Cohort(s) (n=~50 subjects)
o
Population: 

Subjects with relapsed/refractory MM (up to 40 subjects)

Subjects with lymphomas expressing BCMA (up to 10 subjects)
o
Objective: Further evaluate the safety, PK, immunogenicity, and clinical activity of 
GSK2857916 at the RP2 dose identified in Part 1
o
MM and Lymphoma expansion cohorts will be analyzed separately
o
Sparse PK samples will be collected from all subjects

Genetics research samples will be collected predose from all subjects


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Overview of Study Design and Key Features
Dosing

Part 1 Dose Escalation
Initially, GSK2857916 will be administered (IV) via 60 min infusion once every three 
weeks (21 days = 1 cycle) on Schedule 1. Once an MTD1 or RP2D has been 
established on the once every 21-day (Schedule 1), the safety, tolerability, PK, and 
PD of once-weekly dosing (Schedule 2) of GSK2857916 may be explored as an 
additional cohort(s).

Part 2: Dose Expansion Phase
Subjects enrolled in Part 2 dose expansion phase will be administered GSK2857916 
at recommended phase 2 dose (RP2D) established based on Part 1 outcomes.
Time & 
Events

Refer to Appendix 2: Schedule of Activities
Treatment 
Assignment

This is a non-randomized open-label study.
Interim 
Analysis

Part 1: Dose Escalation Phase
No formal interim analysis is planned for Part 1. Safety, pharmacokinetic and 
pharmacodynamic marker data will be examined on an ongoing basis to support dose 
escalation decisions.

Part 2: Dose Expansion Phase
o
For MM cohort, one futility analysis based on ORR data was performed after 
approximately 30 subjects are evaluable (originally 3 futility analyses are planned 
after approximately 15, 22 and 30 subjects are evaluable).
The number of confirmed responses (PR or better) observed will be compared 
with the stopping rules provided in Section 13.6.2 of the protocol.
o
For the lymphomas expressing BCMA cohort, no interim analyses will be 
performed, though consideration would be given to closing the cohort should the 
enrolment be stopped in the MM cohort.
2.4.
Statistical Hypotheses / Statistical Analyses
No formal statistical hypotheses will be tested in Part 1. Analysis of the data obtained 
from Part 1 will only utilize descriptive methods. In Part1, dose escalation/de-escalation 
decisions will be informed by the Bayesian approach: N-CRM (Neuenschwander-
Continuous Reassessment Method) [Neuenschwander, 2008]. Details of the N-CRM 
model used for this study is described in Section 3.1.1. 
The assumption for ORR in part 2 MM cohort is:
The null hypothesis H0: ORR ≤ 20% 
The alternative hypothesis HA: ORR ≥ 40%. 
No hypothesis testing is planned for part 2 MM cohort. The methodology utilized is 
based on the predictive probability of success if enrollment continues to 40 subjects [Lee, 
2008]. The predictive probability design is similar to a Green-Dahlberg design in that it 
allows for early stopping for futility. The differences are that the predictive probability 
design allows for evaluation of stopping rules as often as after each subject, rather than at 
only two stages.  While the two designs have similar type I and type II error rates, the 


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probability of early termination is greater with the predictive probability design. In this 
particular study, one futility analysis based on ORR data was performed after 
approximately 30 subjects are evaluable (originally 3 futility analyses are planned after 
approximately 15, 22 and 30 subjects are evaluable).
3.
PLANNED ANALYSES
3.1.
Interim Analyses
3.1.1.
Part 1: Dose Escalation Phase
While no formal interim analysis is planned for Part 1, safety, pharmacokinetic and 
pharmacodynamic marker data will be examined on an ongoing basis to support dose 
escalation decisions. Prior to determining the GSK2857916 dose for the next cohort 
enrolled, exploratory analysis will be conducted to assess the relationship of 
GSK2857916 dose levels with safety, PK and PD parameters using all data from 
available cohorts. 
Dose escalation/de-escalations decisions will take into account all available data, 
including but not limited to the safety parameters, PD and PK data of all cohorts 
assessed. Dose escalation/de-escalation decisions will be informed by the N-CRM 
(Neuenschwander-Continuous Reassessment Method) [Neuenschwander, 2008]. The N-
CRM model used for Schedule 1 is described in detail in Section 3.1.1.1 and Section 
3.1.1.2. The method is fully adaptive and makes use of all DLT information available at 
the time of each dose assignment. 
3.1.1.1.
Description of the New Continual Reassessment Method
The N-CRM is a type of Bayesian adaptive dose-escalation scheme that estimates the 
parameters of a statistical model relating dose and toxicity, and is expected to locate the 
MTD efficiently while minimizing the number of subjects exposed to pharmacologically 
inactive or unsafe dose levels. The method is fully adaptive and makes use of all the 
toxicity information available at the time of each dose assignment. N-CRM estimates 
may be provided at dose escalation meetings as supportive material to the primary 3+3 
dose escalation design.
The N-CRM estimates, for each potential dose, the (Bayesian) posterior probabilities that 
the DLT rate lies in each of four predefined toxicity ranges:

A dose falls in the Under-dosing range if the rate of a DLT at the dose is in the 
interval [0%, 16%).

A dose falls in the Target toxicity range if the rate of a DLT at the dose is in the 
interval [16%, 33%).

A dose falls in the Excessive toxicity range if the rate of a DLT at the dose is in the 
interval [33%, 60%).


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
A dose falls in the Unacceptable toxicity range if the rate of a DLT at the dose is in 
the interval [60%, 100%].
Additionally, the following over-dose constraints for the recommended dose will be 
maintained: 

The posterior probability of the DLT rate lying in the Excessive Toxicity or 
Unacceptable Toxicity range is 0.25 or less. 

The recommended dose is no more than 2 times that of the previous dose. 

Note that a de-escalation recommendation is possible using this method. At the time 
of each dose-escalation decision, the dose with the highest posterior probability of 
lying in the Target Toxicity range (subject to the given constraints) will be the 
model-recommended dose for the next cohort.
The N-CRM procedure for Schedule 1 will utilize a single subject/cohort run-in phase.
The single subject (small cohort) run-in will be halted when the first ≥ Grade 2 toxicity 
for which relationship to the investigational agent cannot be ruled out occurs in one 
subject in Cycle 1 (21 days).  At this point, the cohort will be expanded to 3 or more 
subjects at the same dose level and the escalation will continue to follow the N-CRM 
procedure as outlined in Table 2
Table 2
Single Subject (Small Cohort) Run-In Procedure for GSK2857916 
given on Schedule 1 (once every 21 days)
Dose Level 
Number of subjects 
with ≥G2 toxicity
Dose Escalation/Action
Dose Level 1/Cohort 1
0 out of 1 subject
(Sentinel subject)
Predicted starting dose 0.03 mg/kg every 21 days
Dose Level 2/Cohort 2
0 out of 1 subject
Escalate to the next dose level with increase   
≤100%  of the starting dose
Dose Level 3 and 
beyond/Cohort 3 and 
beyond
0 out of 1 subject
Escalate to the next dose level with increase of 
≤100% of the dose tested in the previous cohort 
1 out of 1 subject*
Switch to Cohort size of 3 or more subjects 
*Increase of doses up to 100% of the previous dose may continue until the first ≥ Grade 2 toxicity for which 
relationship to the investigational agent cannot be ruled out occurs in one subject in Cycle 1 (21 days).  At this point the 
single subject (small cohort) run-in is halted.  Continue with N-CRM, with cohort sizes of 3 or more subjects.  Increase 
of doses 100% will be considered for subsequent cohorts of 3 or more subjects. 
3.1.1.2.
Prior Probability Distribution 
Elicited prior probabilities of a DLT at each dose were used to determine the prior 
distribution of the parameters of an explicit logistic dose-toxicity model, namely
m,


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where pd is the probability of a DLT at dose d, and dm is a reference dose. 
The prior distribution of (, ln()) will be assumed to be bivariate normal with means 
(standard deviations):  E[]=-1.3281 (1.7153), E[ln()]=-0.795 (1), with correlation 
between and ln() set to ρ=-0.9352 and dm=0.72 mg/kg.
3.1.1.3.
Displays To Be Created For Dose Escalation Review
Review of preliminary data will be performed after completion of each dosing cohort in 
Part 1. Preliminary safety and study population data may include a demographic 
summary, adverse event (AE) summary, AE summary by maximum toxicity category, 
SAE listing, listing of AEs that are reported to be DLT’s, and listing of AEs leading to 
dose modification. Spreadsheets containing relevant study data may also be supplied by 
the study data manager.
Further, after single subject run-in was halted, after each expanded cohort in dose 
escalation, the recommended dose from the N-CRM method and updated posterior 
estimates of the probabilities of being in each dose-toxicity range may be provided. The 
Fixed and Adaptive Clinical Trial Simulator (FACTS) (Version 2.4 or higher) software 
from Tessella will be used to make N-CRM calculations. 
Prior to determining a dose for the next cohort, exploratory analyses will be conducted to 
assess the relationship of dose levels with safety, PK, and pharmacodynamic parameters 
using all data from available cohorts.
The GSK study team, in collaboration with study investigators, will review all relevant 
data to support:

whether the current dose had acceptable toxicity, and

the decision regarding the next dose level based on the totality of the data
3.1.2.
Part 2 Expansion Phase
3.1.2.1.
Multiple Myeloma Expansion Cohort
During Part 2 (Expansion Cohort), futility analyses of response data will be conducted in 
order to determine whether the futility criteria for stopping have been met. The study will 
not be stopped early for efficacy, but is designed to stop early for futility if the predictive 
probability of success is less than 5%.
For Multiple Myeloma cohort, response data will be reviewed once approximately 30 
subjects are evaluable at the RP2D dose and the number of confirmed responses (PR, 
VGPR, CR, and sCR) will be compared with the stopping rules provided in Table 3 based 
on predictive probability design of Lee et al. [Lee, 2008].
In addition to considering the recommendations of the futility analyses, final decisions on 
stopping enrolment in the MM cohort will depend on the totality of the data collected. 
Should the recommendation to stop for futility be disregarded in favour of a decision to 


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continue the trial based on the totality of the data, the overall type I error rate of the 
expansion phase will be inflated.
Table 3
Futility Stopping Region for Multiple Myeloma Expansion Cohort
Number of Overall Responses
Number of Evaluable Subjects
0
1
2
3
4
5
6
7
8
9
10
11
>11
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
3.1.2.1.1.
Operating Characteristics of the Stopping Rules for Futility
The stopping rule in Table 3 is based on the methodology of Lee et al. [Lee, 2008]. For 
the MM expansion cohort, starting with 15 subjects and allowing for a maximum sample 
size of 40, this design will have a type I error rate of 0.075 and 89.8% power. Under the 
null hypothesis, if the true response rate is 20%, the expected sample size of the design is 
23.4 subjects and probability of early termination (PET) is 88.9%.  Under the alternative 
hypothesis, if the true response rate is 40%, the expected sample size of the design is 38.6 
subjects and probability of early termination (PET) is 8.5%.
3.1.2.2.
Lymphoma Expansion Cohort
No interim analyses will be performed on the BCMA positive lymphomas cohort; though 
consideration would be given to closing the cohort should the enrolment be stopped in the 
MM cohort.


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3.2.
Administrative Interim Analyses
Additional administrative interim analysis may be performed to inform patient safety and 
efficacy of the drug as needed.
3.3.
Final Analyses
The final planned primary analyses will be performed after the completion of the 
following sequential steps:
1.
All participants have completed the study as defined in the protocol.
2.
All required database cleaning activities have been completed and final database 
release (DBR) and database freeze (DBF) has been declared by Data Management.
A final analysis of the MM population can be done separately, before the NHL cohort 
completes, and will necessitate separate DBR/DBF activities.


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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 (Reserve, Not Used) 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.

Sub-populations:
o
Part 1: all Part 1 subjects of All Treated 
population. Note, subjects in Part 1 are 
exclusively multiple myeloma patients. (2.5 mg/kg 
will be included in Part 1)
o
Part 2 MM: all Part 2 MM subjects of All Treated 
population
o
All Treated MM: comprise of subjects in Part 1 
and Part 2 MM.
o
Part 2 NHL: all Part 2 lymphoma subjects of All 
Treated population.

Study Population

Safety

Efficacy
Evaluable (MM)

This population is a subset of the ‘All Treated’ 
population, who were initially treated at RP2D in the 
expansion cohort and have at least two post-baseline 
disease assessments or they have progressed or died 
or permanently discontinued treatment. 

futility analyses of 
MM Expansion 
cohort only
DLT Evaluable

All subjects fulfilling the ‘All Treated’ population 
criteria, and having met the following adequate 
exposure criteria: 
o
For Schedule 1 (once every 3 weeks dosing) 
subjects received a complete infusion in cycle 1. 
o
For Schedule 2 (once weekly dosing for 3 
consecutive weeks, 1 week rest) subjects receive 
three infusions, two of which must be complete 
infusions, in cycle 1. (as increases up to ≤30% 
are implemented between cohorts, less than 2 
complete infusions would result in a total dose 
closer to the previous dose investigated). 
(Schedule 2 was not explored in the study)
o
Any subject in the “All Treated” population who 
experiences a DLT, as defined in Section 3.3.3 of 
the protocol will also be included in the DLT 
evaluable population regardless of exposure. 

Summary of DLT, 
for Part 1 only


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Population
Definition / Criteria
Analyses Evaluated
Pharmacodynamic 

The ‘Pharmacodynamic (PD) Population’ is defined as 
those subjects in the “All Treated” population from 
whom at least one PD sample was obtained, 
analyzed, and was measurable.

PD
Pharmacokinetic 
(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
Refer to Appendix 12: List of Data Displays which details the population used for each display.
4.1.
Protocol Deviations
Important protocol deviations (including deviations related to study inclusion/exclusion 
criteria, conduct of the trial, patient management or patient assessment) will be 
summarised and listed.
Protocol deviations will be tracked by the study team throughout the conduct of the study 
in accordance with the Protocol Deviation Management Plan [08May2017, Version 6.0].
o Data will be reviewed prior to freezing the database to ensure all important 
deviations are captured and categorised on the protocol deviations dataset. 
o This dataset will be the basis for the summaries and listings of protocol 
deviations.
A separate summary and listing of all inclusion/exclusion criteria deviations will also be 
provided. This summary will be based on data as recorded on the inclusion/exclusion 
page of the eCRF.


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5.
CONSIDERATIONS FOR DATA ANALYSES AND DATA
HANDLING CONVENTIONS
5.1.
Study Treatment & Sub-group Display Descriptors
Treatment Group Descriptions
RandAll NG
Data Displays for Reporting 
Code
Description [1]
Description [2]
Data Display
Order in TLF 
A
Active 
Treatment
GSK2857916 0.03 mg/kg (Part 1 MM) 
0.03 mg/kg  
1
GSK2857916 0.06 mg/kg (Part 1 MM)  
0.06 mg/kg  
2
GSK2857916 0.12 mg/kg (Part 1 MM)  
0.12 mg/kg  
3
GSK2857916 0.24 mg/kg (Part 1 MM)
0.24 mg/kg  
4
GSK2857916 0.48 mg/kg (Part 1 MM)
0.48 mg/kg  
5
GSK2857916 0.96 mg/kg (Part 1 MM)
0.96 mg/kg  
6
GSK2857916 1.92 mg/kg (Part 1 MM)
1.92 mg/kg
7
GSK2857916 2.50 mg/kg (Part 1 MM)
2.50 mg/kg
8
GSK2857916 3.40 mg/kg (Part 1 MM)
3.40 mg/kg
9
GSK2857916 4.60 mg/kg (Part 1 MM)
4.60 mg/kg
10
GSK2857916 3.40 mg/kg (Part 2 MM)
3.40 MM
11
GSK2857916 3.40 mg/kg (Part 2 NHL)
3.40 NHL
12
Notes: 
[1] This is a single-arm study and only active treatment is planned for the study.
[2] Part 1: dose escalation phase; Part 2: Expansion Cohort; MM: multiple myeloma; NHL: Lymphoma.
5.2.
Baseline Definitions
For all endpoints (except as noted in baseline definitions) the baseline value will be the 
latest pre-dose assessment with a non-missing value, including those from unscheduled 
visits. If time is not collected, Day 1 assessments are assumed to be taken prior to first 
dose and used as baseline.
For subjects who did not receive study treatment during the study, baseline will be 
defined as the latest, non-missing collected value.
For ECG analyses, subject level baseline is defined as the mean of triplicate baseline 
assessments.
Unless otherwise stated, if baseline data is missing no derivation will be performed and 
baseline will be set to missing.


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5.2.1.
Examination of Subgroups
The list of subgroups may be used in descriptive summaries. Additional subgroups of 
clinical interest may also be considered.
Subgroup
Categories 
Age
18 to <65, 65 to <75, >=75
Sex
Male, Female
Ethnic Background
White, Other
ISS Staging at Screening
I, II, III, Other (Unknown or Missing)
Number of prior lines of therapy
<=3,4-5, >5
Type of myeloma
IgG, Non-IgG
Prior Daratumumab Treatment
Yes, No
Refractory to prior anti-cancer 
therapy
Any Proteasome Inhibitor (PI)
Bortezomib
Carfilzomib
Ixazomib
Any Immunomodulator (IMiD)
Thalidomide
Lenalidomide
Pomalidomide
Monoclonal Antibodies
Daratumumab
       Daratumumab alone [2]
       Daratumumab in combination [3]
PI+IMiD
Daratumumab+PI+IMiD
Cytogenetics Risk [1] [3]
High, Other (non-high risk, not done, or missing)
Prior anti-cancer therapy of 
interest

With prior Daratumumab Treatment and Refractory to Both IMiDs 
and Proteasomes Inhibitors.

Without prior Daratumumab Treatment.

Refractory to Both IMiDs and Proteasomes Inhibitors.
NOTES:
[1] A subject is considered as high risk if the subject has any of the following cytogenetics: t(4;14), del17p, 
t(14;16).
[2] Defined as prior CTX regimen with Daratumumab as the only drug the regimen.
[3] Defined as prior CTX regimen with Daratumumab and other drugs.


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5.3.
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
16.3
Appendix 3: Assessment Windows
16.4
Appendix 4: Study Phases and Treatment Emergent Adverse Events
16.5
Appendix 5: Data Display Standards & Handling Conventions
16.6
Appendix 6: Derived and Transformed Data
16.7
Appendix 7: Reporting Standards for Missing Data
16.8
Appendix 8: Values of Potential Clinical Importance


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6.
STUDY POPULATION ANALYSES
6.1.
Overview of Planned Study Population Analyses
The study population analyses will be based on the “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, 
and exposure and treatment compliance will be based on GSK Core Data Standards.  
Details of the planned displays are presented in Appendix 12: List of Data Displays.
6.2.
Disposition of Subjects
A summary of the number of subjects in each of the analysis populations described in 
Section 4 will be provided (for final analysis, Evaluable population will not be included). 
In addition, the number of subjects enrolled by center will be summarized by Study Part 
and Tumor Type using the “Enrolled” population. A separate summary for exclusions 
from each study population will be displayed (for final analysis, Evaluable population 
will not be included). A listing of subjects excluded from analysis populations will also 
be provided.
A summary of subject status and reason for study withdrawal will be provided. This 
display will show the number and percentage of subjects who withdrew from the study, 
including primary reasons for study withdrawal. Reasons for study withdrawal will be 
presented in the order they are displayed in the eCRF. 
A summary of study treatment status will be provided. This display will show the number 
and percentage of subjects who are ongoing or discontinued study treatment and a 
summary of the primary reasons for discontinuation of study treatment. Reasons for study 
treatment discontinuation will be presented in the order they are displayed in the eCRF. A
listing of study treatment discontinuation will be generated. The listing will include last 
dose date, and reasons for study treatment discontinuation. 
6.3.
Demographic and Baseline Characteristics
The demographic characteristics (e.g., age, race, ethnicity, sex, baseline height, and 
baseline body weight and baseline BMI will be summarized and listed. Age, height,
weight and BMI will be summarized using the mean, standard deviation, minimum, 
median, and maximum. The count and percentage will be computed for sex and ethnicity.
Race and racial combinations will be summarized and listed.
Disease history and characteristics (e.g. time since initial diagnosis in years, stage at 
initial diagnosis, date of initial diagnosis) at initial diagnosis and screening will be listed. 
Separate summaries of disease characteristics at initial diagnosis and screening will be 
provided. Disease characteristics 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 summarized and listed.


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Medical conditions present at screening will be listed and will be summarized by past and 
current and by cancer-related and non-cancer related categories. 
Genetic characteristics for multiple myeloma subjects at screening will be summarized 
and listed. Cytogenetic risk for multiple myeloma subjects at screening will be 
summarized. A subject is considered as having high cytogenetic risk if the subject has 
any of the following cytogenetics: t(4;14), del17p, t(14;16).
Substance use, including smoking history and alcohol use will be summarized and listed.
Prior anti-cancer therapy will be coded using GSK Drug coding dictionary, then 
summarized by type of therapy and listed. A listing of prior anti-cancer therapy will show 
the relationship between ATC Level 1, Ingredient, and verbatim text. A summary of the 
best response to the most recent prior anti-cancer therapy will be provided. A summary of 
the number of prior anti-cancer therapy regimens will also be produced. 
Prior anti-cancer therapy for multiple myeloma subjects will also be summarized by type 
of therapy, drug class and subclass. A summary of multiple myeloma subjects refractory 
to prior anti-cancer therapy by drug class will be provided. 
A multiple myeloma subject is defined to be refractory to prior anti-cancer therapy if 
[1] the subject’s best response to prior anti-cancer therapy is PD or SD, OR
[2] the subject’s most recent response to prior anti-cancer therapy is PD or SD, OR
[3] the subject progress within 60 days of completion of prior anti-cancer therapy.
Summary of subjects with multiple myeloma double refractory to prior 
Immunomodulator (IMID) and Proteasome Inhibitor (PI) will also be provided. For 
definition of “double refractory”, IMID and PI are not necessary to be in the same 
regimen.
Anti-cancer radiotherapy will be listed. Prior cancer and non-cancer related surgeries will 
be summarized. Prior and on treatment cancer and non-cancer related surgeries will be 
listed. 
6.4.
Treatment Compliance
Summaries of study treatment exposure and dose modifications (e.g., number of dose 
reductions, number of dose interruptions) will further characterize compliance. These 
analyses are described in Section 6.5 ‘Extent of Exposure’.
6.5.
Extent of Exposure
Extent of exposure to GSK2857916 will be summarized.
The number of cycles administered to study treatment will be summarised with mean, 
median, standard deviation, minimum, and maximum. The number and percentage of 
subjects who received a given number of cycles (<4, 4, and >4 cycles) will be reported. 


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Dose intensity (dose delivered per cycle) will be summarized using mean, median, 
standard deviation, minimum, and maximum by cycle and overall. Dose intensity is the 
cumulative actual dose divided by the total number of cycles across the entire treatment 
period. 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 1-21, 22-42 and >42 days will 
be computed. Primary reasons for dose reductions and dose delays will also be 
summarized by cycle. 
Duration of delays is defined as period from the expected start date of dose to actual start 
date of current dose. Calculation: (actual start date of current dose - expected start date of 
dose). Expected start date of dose = actual start date of previous dose + 21.
The summaries of dose modifications will be provided only if the data warrant.
All the dose reductions, dose escalations, infusion interruptions, incomplete infusions and 
dose delays will be listed separately.
A plot showing the number and percentage of subjects treated at different dose levels 
over time will be provided.
The duration of exposure to study treatment in days (from first day to last day of 
treatment) will be calculated. A horizontal bar graph of duration of treatment will be 
produced that displays duration of treatment in days for each subject.
6.6.
Concomitant Medications
Concomitant medications will be coded using GSK Drug coding dictionary, summarized, 
and listed. The summary of concomitant medications will show the number and 
percentage of subjects taking concomitant medications by Ingredient. Multi-ingredient 
products will be summarized by their separate ingredients rather than as a combination of 
ingredients. Anatomical Therapeutic Chemical (ATC) classification Level 1 (Body 
System) information will be included in the dataset created but will not appear on the 
listing or summary. 
Prophylactic Medication for Infusion-Related Reactions will be summarized by drug 
class and drug name and listed separately. Eye medications will be listed.
In the summary of concomitant medications, each subject is counted once within each 
unique ingredient. For example, if a subject takes Amoxycillin on two separate occasions, 
the subject is counted only once under the ingredient “Amoxycillin”. In the summary of 
concomitant medications, the ingredients will be summarized by the base only, using 
CMBASECD and CMBASE. Note: In order to be considered a concomitant medication, 
the concomitant medication must have been taken at some point during the on-therapy 
window.


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Blood products or blood supportive care products with onset date within the on-therapy 
window will be included in the summary tables. The frequency and percentage of 
subjects using blood products and blood supportive care products after the start of study 
medication will be provided. Supporting listings will also be provided.
6.7.
Subsequent Anti-Cancer Therapies
The number and percentage of subjects that received chemotherapy, immunotherapy, 
hormonal therapy, biologic therapy, radioactive therapy, small molecule targeted therapy, 
as post study treatment anti-cancer therapy will be summarized. Time from study 
treatment discontinuation to the first post study treatment anti-cancer therapy will also be 
included in this summary table. 
Follow-up anti-cancer therapy will be coded using GSK Drug coding dictionary, then 
summarized by ingredient. A listing of the type of follow-up anti-cancer therapy received 
(chemotherapy, immunotherapy, hormonal therapy, biologic therapy, radioactive therapy, 
and small molecule targeted therapy for each subject will be provided).


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7.
EFFICACY ANALYSES
7.1.
Primary Efficacy Analyses
No primary efficacy analyses were planned.
7.2.
Secondary Efficacy Analyses
Details of the planned displays are provided in Appendix 12: List of Data Displays and 
will be based on GSK data standards and statistical principles.
Unless otherwise specified, endpoints / variables defined in Section 7.2.1.1 and Section 
7.2.2.1 will be summarised using descriptive statistics, graphically presented (where 
appropriate) and listed.
7.2.1.
Multiple Myeloma
7.2.1.1.
Endpoint / Variables
7.2.1.1.1.
Overall Response Rate
Overall Response Rate (ORR), is defined as the percentage of responders (subjects with 
confirmed stringent complete response (sCR), complete response (CR), very good partial 
response (VGPR), and partial response (PR) as assessed according to 2011 International 
Myeloma Working Group (IMWG) criteria (Appendix 1 in the protocol) ). Only the 
assessments from the start of treatment up to the earlier of disease progression or the start 
of new anti-cancer therapy will be considered. Only new systemic anti-cancer drugs 
taken are considered as anti-cancer therapy (radiotherapy and surgeries are not 
considered as systemic anti-cancer therapy for the purpose of this analysis). . 
Subjects with only one assessment (therefore not confirmed), or assessments of Not 
Evaluable or missing response will be treated as non-responders; i.e. they will be 
included in the denominator when calculating the percentage.
7.2.1.1.2.
Response Confirmation Algorithm
The definitions and details to derive unconfirmed and confirmed response are outlined 
below. For both confirmed and unconfirmed response derivations, only responses 
assessments from the start of treatment up to the earlier of disease progression or the start 
of new anti-cancer therapy will be considered. Date associated with response was defined 
in Section 16.5.5
Definitions:
1. The hierarchy of response classifications from high to low is as following: 
sCR, CR, VGPR, PR, MR, SD, PD and NE. Response was assessed according 
to the 2011 Uniform Criteria Consensus recommendations of the International 
Myeloma Working Group (See Appendix 1 of protocol).


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2. Definition of two consecutive assessments: the two consecutive assessments 
should be taken from two different samples, and NOT based upon the splitting 
of a single sample.
a.
No minimum time separation between two consecutive assessments is 
required to confirm response.
b. If there are two assessments separated by not evaluable (NE) or 
Missing assessment(s), collapse data by ignoring NE or Missing 
assessments. 
c.
If two consecutive assessments are on different dates, it is assumed 
that the two assessments are from different samples
d. If there are multiple assessments on the same date and there is no data 
to show that they are from different samples, it is assumed these 
assessments are from the same sample. Then only the response with 
the lowest magnitude will be selected as the response for that date.
Two-step algorithm for determining the best confirmed response
Step1. Determine the confirmed response sequentially at each time of disease assessment.
A. For confirmed sCR, CR, VGPR, PR, MR, SD, two consecutive assessments are 
required. 
a.
For any two consecutive assessments with different magnitudes, the confirmed 
response is the response of lower magnitude.
b. For any two consecutive assessments with the same magnitude, the confirmed
response is the response of that magnitude.
c.
Although the response will be confirmed at the time of the second one of the two 
consecutive assessments, the date of the first one of the two consecutive 
assessments will be the date of this confirmed response.
Table 4
Summary of the criteria for confirmation of sCR, CR, VGPR, PR, MR, 
SD
Response at one time-point of two 
consecutive assessments
Response at the other time-point 
of two consecutive assessments
Confirmed 
Response
sCR/CR/VGPR/PR/MR/SD
SD
SD
sCR/CR/VGPR/PR/MR
MR
MR
sCR/CR/VGPR/PR
PR
PR
sCR/CR/VGPR
VGPR
VGPR
sCR/CR
CR
CR
sCR
sCR
sCR


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B. For PD, since for this study, no confirmation of PD is required, only one PD 
assessment is required. Any PD assessment will be confirmed by itself at the time of 
the PD’s assessment.
C. If the subject has only one non-PD /non-NE assessment then the confirmed response 
is NE at the date of that assessment.
D. If all assessments were NE then the confirmed response is NE at the date for each 
assessment.
Step 2. Determine the best overall confirmed response in Step 1. If assessments at all 
visits are missing then the best confirmed response is NE.
Examples: 
Example 1.
Step1. 
Visit
Response
Confirmed 
response
1
PR
2
SD
SD
3
SD
SD
Step 2. 
The best overall confirmed response is SD 
Example 2.
Step1. 
Visit
Response
Confirmed 
response
1
VGPR
2
NE
3
NE
4
PR
PR
Step 2. 
The best overall confirmed response is PR 


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Example 3.
Step1. 
Visit
Response
Confirmed 
response
1
sCR
2
sCR
sCR
3
CR
CR
4
PR
PR
Step 2. 
The best overall confirmed response is sCR 
Example 4.
Step1. 
Visit
Response
Confirmed 
response
1
sCR
2
CR
CR
3
CR
CR
4
PR
PR
Step 2. 
The best overall confirmed response is CR 
Example 5.
Step1. 
Visit
Response
Confirmed 
response
1
CR
2
VGPR
VGPR
Step 2. 
The best overall confirmed response is VGPR.


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7.2.1.2.
Summary Measure
Overall response rate (ORR) and the associated 2-sided 95% exact confidence intervals 
will be provided by dose level and study part. In addition, Clinical Benefit Rate (CBR), 
defined as the percentage of subjects with minimal response (MR) will be summarized 
in the same way as ORR by dose level and study part. Unconfirmed response summaries 
may be provided for interim analyses. A list of investigator-assessed response at each 
visit will be listed.
7.2.1.3.
Population of Interest 
The secondary efficacy analyses will be based on the “All Treated” population, unless 
otherwise specified. Response data for multiple myeloma will be summarized by Study 
Part using the All Treated MM population and in subgroup: Prior anti-cancer therapy of 
interest as defined in Section 5.2.1.
7.2.2.
Lymphoma
7.2.2.1.
Endpoint / Variables
7.2.2.1.1.
Overall Response Rate
For lymphoma patients, clinical activity for lymphomas will be calculated based on ORR 
defined as the percentage of subjects with confirmed CR or PR, as described in the 
Revised Response Criteria for Malignant Lymphoma (RRCML, Appendix 2 in the 
protocol) from the start of treatment until disease progression or the start of new anti-
cancer therapy. 
A summary of investigator-assessed best response with confirmation will be presented. 
Subjects with Not Evaluable or missing response will be treated as non-responders; and 
they will be included in the denominator when calculating the percentage. To be assigned 
a status of complete response or partial response, all responses must be confirmed by 
repeat assessments performed no less than four weeks after the criteria for CR or PR were 
met (RRCML, Appendix 2 in the protocol).
7.2.2.2.
Summary Measure
Overall response rate and the associated 2-sided 95% exact confidence intervals will be 
provided. A list of investigator-assessed response at each visit will be listed.
7.2.2.3.
Population of Interest 
The secondary efficacy analyses will be based on the “All Treated” population, unless 
otherwise specified. Response data for lymphoma will be summarized using the Part 2 
NHL population.
7.2.3.
Strategy for Intercurrent (Post-Randomization) Events
Not applicable to this study.


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7.2.4.
Statistical Analyses / Methods
Details of the planned displays are provided in Appendix 12: 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.
7.3.
Exploratory Efficacy Analyses
7.3.1.
Multiple Myeloma
7.3.1.1.
Endpoint / Variables
Time-to-event endpoint - Multiple Myeloma
Progression-Free 
Survival (PFS)
defined as the time from first dose until the earliest date of confirmed 
disease progression (PD) per IMWG (2011), or death due to any cause.
Time to 
Progression (TTP)
defined as the time from first dose until the earliest date of PD per IMWG 
(2011), or death due to PD.
Duration of 
Response (DOR)
defined as the time from first documented evidence of confirmed PR or 
better until the time when disease progression (PD) is documented per 
IMWG (2011), or death due to PD among subjects who achieve a 
response (i.e. confirmed PR or better). 
Time to Response 
(TTR)
defined as the time between the date of first dose and the first documented 
evidence of confirmed response (PR or better), among subjects who 
achieve a response (i.e., confirmed PR or better). 
Time to Best 
Response (TTBR)
defined as the time between the date of first dose and the best confirmed 
response (PR or better), among subjects who achieve a response (i.e., 
confirmed PR or better).
Overall survival 
(OS)
defined as the time from the date of first dose until death from any cause.
In addition, monoclonal protein and serum free light chain lab test values will be plotted. 
Subgroup analysis for ORR will be performed 
7.3.1.2.
Summary Measure
7.3.1.2.1.
Progression-Free Survival
PFS is defined as the interval of time between the date of first dose and the earlier of the 
date of first disease progression and the date of death due to any cause. Disease 
progression will be based on the assessments by the Investigator. 
If there is no adequate baseline assessment, the subjects will be censored at their date of 
first dose. Subjects without any adequate post-baseline tumor assessments will be 
censored at the date of first dose.


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Subjects who progressed or died after an extended period without adequate assessment 
will be censored at their date of last adequate assessment prior to progression or death 
even if subsequent information is available regarding progression or death. An adequate 
assessment is defined as an assessment where the Investigator determined response is 
sCR, CR, VGPR, PR, MR or SD. The date of response at that assessment will be used for 
censoring. As the assessment schedule may change through the course of the protocol, 
specific rules for identifying extended loss to follow-up or extended time without an 
adequate assessment are provided in Section 16.5.4.
For subjects who receive subsequent anti-cancer therapy the following rules will apply:

If the start date of the anti-cancer therapy is partial (i.e. either missing the day but 
has the month and year available or missing both day and month), the imputation 
rules described in Section 16.7.2.1 will be applied. No imputation will be made for 
completely missing dates.

If anti-cancer therapy is started without documented disease progression or death OR 
is started prior to documented disease progression or death, then PFS will be 
censored at the date of the last adequate assessment that is no later than the date of 
initiation of anti-cancer therapy (i.e. if an assessment occurs on the same day as the 
start of new anti-cancer therapy the assessment will be used - as it will be assumed 
the assessment occurred prior to the administration of new anti-cancer therapy). The 
date of response at the last adequate assessment will be used as the censoring value.

If a subject has only a baseline visit or does not have an adequate assessment that is 
no later than the date of initiation of anti-cancer therapy, PFS will be censored at the 
date of first dose.

If a subject has neither progressed nor died nor started new anti-cancer therapy, then 
PFS will be censored at the date of the last adequate assessment defined as an 
assessment where the Investigator determined response is sCR, CR, VGPR, PR, MR 
or SD. The date of response will be used as the censoring date.
A summary of the assignments for progression and censoring dates for PFS are specified 
in Table 5.


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Table 5
Assignments for Progression and Censoring Dates for PFS Analysis
Situation
Date of Event 
(Progression/Death) or 
Censoring 
Outcome Event 
(Progression/Death) Or 
Censored
No (or inadequate) baseline 
tumor assessments [1] and the 
subject has not died (if the subject 
has died follow the rules for death 
indicted at the bottom of the table)
First dose date
Censored
No post-baseline assessments 
and the subject has not died (if 
the subject has died follow the 
rules for death indicted at the 
bottom of the table)
First dose date
Censored
Progression documented 
between scheduled visits
Date of assessment of 
progression [1]
Event
No progression (or death)
Date of last ‘adequate’ 
assessment of response [2]
Censored
New anticancer treatment started 
(prior to documented disease 
progression or death) [3].
Date of last ‘adequate’ 
assessment of response [2] (on or 
prior to starting anti-cancer 
therapy) 
Censored
Death before first PD assessment 
(or Death at baseline or prior to 
any adequate assessments)
Date of death
Event
Death between adequate 
assessment visits 
Date of death
Event
Death or progression after an 
extended loss-to-follow-up time 
(two or more missed cycles + 7 
day window) [4]
Date of last ‘adequate’ 
assessment of response [2] (prior 
to missed assessments)
Censored
[1] In part 1, adequate baseline assessment is defined as at baseline, a patient has at least one of the following 
measurements: a. Serum M-protein or b. Urine M-protein or c. Serum FLC assay or d. Biopsy proven plasmacytoma 
(should be measured within 28 days of Screening Visit). 
In part 2, adequate baseline assessment is defined as at baseline, a patient has at least one of the following 
measurements: a. Serum M-protein ≥0.5 g/dL (≥5 g/L) or b. Urine M-protein ≥200 mg/24h or c. Serum FLC assay: 
Involved FLC level ≥5 mg/dL (≥50 mg/L) and an abnormal serum free light chain ratio (<0.26 or >1.65) or d. Biopsy 
proven plasmacytoma (should be measured within 28 days of Screening Visit and no later than the first dose date).
[2] An adequate assessment is defined as an assessment where the Investigator determined response is sCR, CR, 
VGPR, PR, MR, or SD.
[3] If PD or death and New anti-cancer therapy occur on the same day assume the progression or death was 
documented first (e.g., outcome is progression or death and the date is the date of the assessment of progression or 
death). If anti-cancer therapy is started prior to any adequate assessments, censoring date should be the date of first 
dose.
[4] Refer to section 16.5.4 “Extended Loss to Follow-up or Extended Time without an Adequate Assessment”.
PFS will be summarized using Kaplan-Meier curves. If there are a sufficient number of 
progressions or deaths, median PFS, first and third quartiles and 95% CI, will be 
estimated using the Brookmeyer-Crowley method [Brookmeyer, 1982]. A figure and 
listing of PFS time will also be provided. Summary and figure of PFS will be based on 


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Part 2 MM sub-population and subgroup prior anti-cancer therapy of interest; listing of 
PFS will be based on All Treated MM population.
7.3.1.2.2.
Time to Progression
TTP is defined as the interval of time between the date of first dose and the earlier of the 
date of first documented evidence of PD, or death due to PD, whichever occurs first.
A summary of the assignments for progression and censoring dates for TTP are specified 
in Table 6
Table 6
Assignments for Progression and Censoring Dates for TTP Analysis
Situation
Date of Event 
(Progression/Death) or 
Censoring 
Outcome Event 
(progression/Death) Or 
Censored
No (or inadequate) baseline 
tumor assessments [1] and the 
subject has not died (if the subject 
has died follow the rules for death 
indicted at the bottom of the table)
First dose date
Censored
No post-baseline assessments 
and the subject has not died (if 
the subject has died follow the 
rules for death indicted at the 
bottom of the table)
First dose date
Censored
Progression documented at or 
between scheduled visits
Date of assessment of 
progression [1]
Event
No progression (or death)
Date of last ‘adequate’ 
assessment of response [2]
Censored
New anticancer treatment started 
(prior to documented disease 
progression or death) [3].
Date of last ‘adequate’ 
assessment of response [2] (on or 
prior to starting anti-cancer 
therapy) 
Censored
Death from causes other than 
progression
Date of death
Censored
Death or progression after an 
extended loss-to-follow-up time 
(two or more missed cycles + 7 
day window) [4]
Date of last ‘adequate’ 
assessment of response [2] (prior 
to missed assessments)
Censored
[1] In part 1, adequate baseline assessment is defined as at baseline, a patient has at least one of the following 
measurements: a. Serum M-protein or b. Urine M-protein or c. Serum FLC assay or d. Biopsy proven plasmacytoma 
(should be measured within 28 days of Screening Visit). 
In part 2, adequate baseline assessment is defined as at baseline, a patient has at least one of the following 
measurements: a. Serum M-protein ≥0.5 g/dL (≥5 g/L) or b. Urine M-protein ≥200 mg/24h or c. Serum FLC assay: 
Involved FLC level ≥5 mg/dL (≥50 mg/L) and an abnormal serum free light chain ratio (<0.26 or >1.65) or d. Biopsy 
proven plasmacytoma (should be measured within 28 days of Screening Visit and no later than the first dose date).
[2] An adequate assessment is defined as an assessment where the Investigator determined response is sCR, CR, 
VGPR, PR, MR, or SD.
[3] If PD and New anti-cancer therapy occur on the same day assume the progression was documented first e.g., 
outcome is progression and the date is the date of the assessment of progression). If anti-cancer therapy is started 
prior to any adequate assessments, censoring date should be the date of first dose. Refer to Section 16.5.4 “Extended 
Loss to Follow-up or Extended Time without an Adequate Assessment”.


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TTP will be summarized using Kaplan-Meier curves. If there are a sufficient number of 
progressions or death due to PD, median TTP, first and third quartiles and 95% CI, will 
be estimated using the Brookmeyer-Crowley method [Brookmeyer, 1982]. A figure and 
listing of TTP time will also be provided. Summary and figure of TTP will be based on 
Part 2 MM population; listing of TTP will be based on All Treated MM population.
7.3.1.2.3.
Duration of Response
Duration of Response (DOR) is defined, for subjects with a confirmed response (PR or 
better) as the time between first documented evidence of confirmed response and disease 
progression or death due to PD, whichever occurs first.

Duration of response is derived for patients with a confirmed PR or better only. 

Censoring rules will follow those of the TTP analysis.
DOR will be summarized using Kaplan-Meier curves. If there are a sufficient number of 
progressions or death due to PD among the responders, median DOR, first and third 
quartiles and 95% CI, will be estimated using the Brookmeyer-Crowley method 
[Brookmeyer, 1982]. A figure and listing of DOR time will also be provided. Summary 
and figure of DOR will be based on Part 2 MM population and subgroup: prior anti-
cancer therapy of interest; listing of DOR will be based on All Treated MM population.
7.3.1.2.4.
Time to Response
Time to Response (TTR) is defined as the time from first dose to the first documented 
evidence of confirmed PR or better, among subjects who achieve a response (i.e., 
confirmed PR or better).
TTR will be summarized using Kaplan-Meier method. If data permits, median TTR, first 
and third quartiles and 95% CI, will be estimated using the Brookmeyer-Crowley method 
[Brookmeyer, 1982]. A listing of TTR time will also be provided. Summary of TTR will 
be based on Part 2 MM population; listing of TTR will be based on All Treated MM 
population.
7.3.1.2.5.
Time to Best Response
Time to Response (TTBR) is defined as the time from first dose to the best confirmed 
response (PR or better), among subjects who achieve a response (i.e., confirmed PR or 
better).
TTBR will be summarized using Kaplan-Meier method. If data permits, median TTBR, 
first and third quartiles and 95% CI, will be estimated using the Brookmeyer-Crowley 
method [Brookmeyer, 1982]. A listing of TTBR time will also be provided. Summary of 
TTBR will be based on Part 2 MM population; listing of TTBR will be based on All 
Treated MM population.


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7.3.1.2.6.
Overall Survival
Overall survival (OS) is defined as the time from the date of first dose until death from 
any cause. For subjects who do not die, time of death will be censored at the date of last 
contact.
The protocol is amended to collect long-term survival data (i.e. up to 1 year after last 
subject completes or discontinues treatment). Subjects who are already completed the 
study will be contacted to request re-consent.
If all the patients (who were alive at the time of study completion) can be re-consented, 
OS landmark analysis may be performed at 9 and 12 months using Kaplan-Meier analysis 
as data permits. A listing of OS will also be provided. The OS landmark analysis will be 
based on Part 2 MM population; listing of OS will be based on All Treated MM 
population.
Otherwise, only descriptive analysis (number and % of deaths and lost to follow-up) will 
be performed.
7.3.1.3.
Monoclonal Protein and Serum Free Light Chain
A waterfall plot showing the maximum percent reduction from baseline in Serum M-
protein, or Urine M-protein, or difference between two types Serum FLC [Kappa light 
chain (Kappa LC) and Lambda light chain (Lambda LC)] for each subject will be 
produced using Part1 and Part 2 MM populations. Only the assessments from the start of 
treatment up to the start of new anti-cancer therapy will be considered. Only new 
systemic anti-cancer drugs taken are considered as anti-cancer therapy (radiotherapy and 
surgeries are not considered as systemic anti-cancer therapy for the purpose of this 
analysis). The maximum percent reduction will be plotted in the following hierarchical 
order: 
[1] Plot Serum M-protein maximum percent reduction from baseline if data is 
available;
[2] If [1] is not feasible, plot Urine M-protein maximum percent reduction from 
baseline if data is available;
[3] If both [1] and [2] are not feasible, plot maximum percent reduction from baseline
for difference between two types of Serum FLC if data is available;
Difference between two types Serum FLC
The percent change from baseline for difference between two types of Serum FLC is 
defined as: 
(post-baseline difference-baseline difference) / baseline difference *100%
To calculate the difference, the “involved” and “non-involved” light chains must be 
determined at first based on the ratio of non-missing values for Serum Kappa LC protein 
and Serum Lambda LC protein at baseline.


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Detailed algorithm is provided as below:

If the baseline ratio of (Kappa LC/Lambda LC)>1.65, then Kappa LC is defined as 
involved FLC, and Lambda LC is defined as non-involved FLC. Then
o
Difference between involved and uninvolved = Kappa LC-Lambda LC

If the baseline ratio of (kappa/lambda)<0.26, then Lambda light chain is defined as 
involved FLC, and Kappa light chain is defined as non-involved FLC
o
Difference between involved and uninvolved = Lambda LC-Kappa LC

If the baseline ratio of (Kappa LC/Lambda LC) 1.65 and 0.26, then “involved” 
and “non-involved” FLC can not be determined (ratio is normal), and maximum 
percent reduction from baseline for difference between two types of Serum FLC
won’t be available.
In addition, a scatter plot of free soluble BCMA at pre-dose (cycle 1) and maximum 
percent change from baseline in Serum M-protein, Urine M-protein or difference between 
two types Serum FLC will be provided following the hierarchical order specified above.
7.3.1.4.
Subgroup Analysis of ORR
A forest plot of ORR analysis will be provided for the following subgroups: Age, Sex, 
Ethnic Background, ISS Staging at Screening, Number of prior lines of therapy, Type of 
myeloma, Prior Daratumumab Treatment, Refractory to prior anti-cancer therapy, 
Cytogenetics Risk as defined in Section 5.2.1.
7.3.1.5.
Population of Interest 
The secondary efficacy analyses will be based on the “All Treated” population, unless 
otherwise specified (as in Section 4). 
7.3.2.
Strategy for Intercurrent (Post-Randomization) Events
Not applicable to this study.
7.3.3.
Statistical Analyses / Methods
Details of the planned displays are provided in Appendix 12: List of Data Displays and 
will be based on GSK data standards and statistical principles.
Unless otherwise specified, endpoints / variables defined in Section 7.2.1 will be 
summarised using descriptive statistics, graphically presented (where appropriate) and 
listed.


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8.
SAFETY ANALYSES
The safety analyses will be based on the “All Treated” population, unless otherwise 
specified.
8.1.
Adverse Events Analyses
Adverse events analyses including the analysis of adverse events (AEs), Serious (SAEs)
and other significant AEs will be based on GSK Core Data Standards. The details of the 
planned displays are provided in Appendix 12: List of Data Displays.
An overview summary of AEs, including counts and percentages of subjects with any 
AE, AEs related to study treatment, AEs leading to permanent discontinuation of study 
treatment, AE leading to dose reductions, AEs leading to dose delays OR interruptions, 
SAEs, SAEs related to study treatment, fatal SAEs, and fatal SAEs related to study 
treatment will be produced.
A summary of non-serious AEs that occurred in strictly 5% of the subjects or above will 
be provided (no rounding for the percentage will be used in terms of 5% threshold, e.g., 
event with 4.9% incidence rate should not be included in this table). The summary will be 
displayed by SOC and PT.
The relationship between MedDRA SOC, PT, and Verbatim Text will be displayed.
Adverse events (AEs) will be graded according to the CTCAE, Version 4.0. Adverse 
events will be coded to the preferred term (PT) level using the Medical Dictionary for 
Regulatory Affairs (MedDRA dictionary). 
A summary of number and percentage of subjects with any adverse events by maximum 
grade will be produced. AEs will be sorted by Preferred term (PT) in descending order 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 adverse event will be counted only 
once at the maximum grade no matter how many events they have.
In addition, the frequency and percentage of AEs (all grades) will be summarized and 
displayed in two ways: 1) in descending order of total incidence by PT only and 2) in 
descending order of total incidence by System Organ Classes (SOC) and PT and 
Maximum Grade. In the SOC row, the number of subjects with multiple events under the 
same system organ class will be counted once.
A separate summary will be provided for study treatment-related AEs. A study treatment-
related AE is defined as an AE for which the investigator classifies the relationship to 
study treatment as “Yes”. A worst-case scenario approach will be taken to handle missing 
relatedness data, i.e. the summary table will include events with the relationship to study 


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treatment as ‘Yes’ or missing. The summary table will be displayed in descending order 
of total incidence by SOC and PT and Maximum Grade.
All AEs will be listed. Additionally, a listing of subject IDs for each individual AE will 
be produced. 
A listing of adverse events recorded as dose-limiting toxicities will be provided. 
Additionally, a summary of the number of patients experiencing DLT’s in each cohort 
will be provided.
The summary of adverse event by SOC and PT and maximum grade, and AE by PT will 
also be produced for the following subgroups:
Prior anti-cancer therapy of interest: 

With prior Daratumumab Treatment and Refractory to Both IMiDs and Proteasomes 
Inhibitors

Without prior Daratumumab Treatment

Refractory to Both IMiDs and Proteasomes Inhibitors
8.2.
Adverse Events of Interest Analyses
There are no pre-defined Adverse Events of Special Interest in the protocol, as it was a 
first time in human (FTIH) trial. During the course of the study, the analyses of the 
following adverse events of interest were included upon the safety review team (SRT) 
requests.

Corneal events

Thrombocytopenia

Neutropenia

Hematologic Toxicity

Infusion-related Reactions as collected in the eCRF
For Corneal events, Thrombocytopenia, Neutropenia Hematologic Toxicity, a
comprehensive list of MedDRA terms based on clinical review will be used to identify 
each type of event. Changes to the MedDRA dictionary may occur between the start of 
the study and the time of reporting and/or emerging data from on-going studies may 
highlight additional adverse events of interest, therefore the list of terms to be used for 
each event of interest and the specific events of interest will be based on the SRT 
agreements in place at the time of reporting. The details of the planned displays are 
provided in Appendix 12: List of Data Displays.
Summaries of the number and percentage of subjects with these events will be provided 
for each type of events separately by preferred term and maximum grade. The time of 


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onset and duration of first occurrence of each type of events will be summarized using 
summary statistics mean, standard deviation, median, minimum value, and maximum. 
The number and percentage of subjects who have time of onset of first occurrence (1-21, 
22-42, 43-63, >63 days) will be reported. The number and percentage of subjects who 
have duration of first occurrence (1-21, 22-42, >42 days) will be reported.
The summary of event characteristics will also be provided, including number of subjects 
with any event, number of events, number of subjects with any event that is serious, 
number of subjects with any event that is related to study treatment, number of 
occurrences (One, Two, Three or more), maximum grade 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, 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.
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 time of death relative 
to the last dose of medication (>30 days or 30 days) and primary cause of death (disease 
under study, SAE related to study treatment, or other). A supportive listing will be 
generated to provide subject-specific details on subjects who died. 
All SAEs will be tabulated based on the number and percentage of subjects who 
experienced the event. Separate summaries will also be provided for study treatment-
related SAEs. The summary tables will be displayed in descending order of total 
incidence by SOC and PT.
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.
AEs of maximum grade of 3 or higher will be summarized separately by SOC and PT.


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8.4.
Adverse Events Leading to Discontinuation of Study 
Treatment and/or Withdrawal from the Study and Other 
Significant Adverse Events
The following categories of AEs will be summarized separately in descending order of 
total incidence by SOC and PT and separate supportive listings will be generated with 
subject level details for those subjects:

AEs Leading to Permanent Discontinuation of Study Treatment or Withdrawal from 
Study

AEs Leading to Discontinuation of Study Treatment

AEs Leading to Dose Interruptions or Delays

AEs Leadings to Dose Reductions
8.5.
Pregnancies 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be recorded 
as an AE or SAE as described in the protocol. If subjects and subjects’ partner become 
pregnant while on the study, the information will be included in the narratives and no 
separate table or listing will be produced.
8.6.
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 12: List of Data Displays.
Summary of change from baseline by scheduled visits using mean, median, standard 
deviation, minimum and maximum will be provided.
Summaries of worst case grade increase from baseline grade will be provided for all the 
lab tests that are gradable by CTCAE v4.0. These summaries will display the number and 
percentage of subjects with a maximum post-baseline grade increasing from their 
baseline grade. Any increase in grade from baseline will be summarized along with any 
increase to a maximum grade of 3 and any increase to a maximum grade of 4. Missing 
baseline grade will be assumed as grade 0. For laboratory tests that are graded for both 
low and high values, summaries will be done separately and labelled by direction, e.g., 
sodium will be summarized as hyponatremia and hypernatremia.
For lab tests that are not gradable by CTCAE v4.0, summaries of worst case changes 
from baseline with respect to normal range will be generated. Decreases to low, changes 
to normal or no changes from baseline, and increases to high will be summarized for the 
worst case post-baseline. If a subject has a decrease to low and an increase to high during 
the same time interval, then the subject is counted in both the “Decrease to Low” 
categories and the “Increase to High” categories. 


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Separate summary tables for hematology, and chemistry laboratory tests will be 
produced. Liver function laboratory tests will be included with chemical chemistry.
A supporting listing of laboratory data for subjects with abnormalities of potential clinical 
concern will be provided. A separate listing of laboratory data with character values will 
also be provided. For lab test values that can be graded, values of grade 1 or above are 
defined as values of potential clinical concern. For lab test values that can not be graded, 
values out of the normal range are defined as values of potential clinical concern.
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.
8.6.1.
Analyses of Liver Function Tests
Summaries of hepatobiliary laboratory events including possible Hy’s law cases will be 
provided in addition to what has been described above. 
A plot of maximum total bilirubin versus maximum ALT will be generated. Plots of 
maximum AST versus maximum LDH and maximum AST versus maximum Creatinine 
Kinase will be generated.
A Summary of Liver Monitoring/Stopping Event Reporting will be provided. The 
medical conditions data for subjects with liver stopping events will be listed. The 
substance use data for subjects with liver stopping events will be listed.  
8.7.
Other Safety Analyses
The analyses of non-laboratory safety test results including ECGs and vital signs will be 
based on GSK Core Data Standards, unless otherwise specified. The details of the 
planned displays are presented in Appendix 12: List of Data Displays.
Unless otherwise specified, the denominator in percentage calculation at each scheduled 
visit will be based on the number of subjects with non-missing value at each particular 
visit.
Performance Status
ECOG performance status will be summarized at baseline and each post-baseline 
scheduled visit. Summaries will use frequency and percentage of subjects at each planned 
assessment time. A summary of change from baseline by scheduled visits will be 
performed, as well as the worst case post-baseline and the best case post-baseline changes 
during the study (improved, no change, deteriorated).
A supporting listing will also be provided. 


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ECG
A summary of the number and percentage of subjects who had normal and abnormal 
(clinically significant and not clinically significant) ECG findings will be displayed by 
scheduled visits as well as for the worst case post-baseline. 
The QTc values based on Fridericia formula will be rounded to the integer and the values 
will be categorized into the following ranges: Grade 0 (<450), Grade 1 (450-480), Grade 
2 (481-500), and Grade 3 (≥501). Summaries of grade increase will be provided. These 
summaries will display the number and percentage of subjects with any grade increase, 
increase to grade 2 and increase to grade 3 in the worst case post-baseline only. 
The changes in QTc values will be categorized into the clinical concern ranges which are 
specific to changes in QTc: 31-60 and >60 msec. A summary of change in QTc value will 
display the number and percentage of subjects with a change within each range in the 
worst case post-baseline only. Subjects with missing baseline values will be excluded 
from this summary.
A listing of QTc values of potential clinical importance will be provided
The summaries and listing of QTc will use the collected values based on Fridericia 
formula.
A figure plotting the baseline QTc and the worst-case post-baseline values will be 
produced. The figure will have reference lines at 480 and 500 msec for both the ordinate 
and the abscissa axes. There will be diagonal reference lines at equality (i.e. a 45 degree 
line), at equality plus 30 msec, and at equality plus 60 msec.
LVEF
Absolute change from baseline in LVEF will be summarized in the worst case post-
baseline only. Only the post-baseline assessments that used the same method (ECHO or 
MUGA) 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


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LVEF results will also be listed with subject level details including absolute change from 
baseline.
Ocular Exams
For best corrected visual acuity (BCVA), summary statistics for the logMAR score at 
baseline and end of study treatment will be displayed separately by eye using mean, 
median, standard deviation, minimum and maximum. Changes of logMAR score from 
baseline to end of treatment visit, and maximum (worst) change from baseline will be 
summarized based on the following categories: no change/improved vision: a change 
from baseline <0.12; a possible worsened vision: a change from baseline >=0.12 to <0.3; 
a definite worsened vision: a change from baseline >=0.3. Subjects with character values 
of visual acuity exam results will not be included in this summary.
Number and percentage of subjects who experienced corneal clinical signs will be 
summarized. Among subjects who experienced corneal clinical signs, number and 
percentage of subjects with/without reported corneal events will be provided. Visual 
acuity/ abnormal corneal exam results (eye level) at each visit, and incidence of corneal 
clinical signs and reported corneal events (subject level) during the study will be listed. 
The findings considered ‘corneal clinical signs’ were identified from the pre-defined list 
of choices in the eCRF. 
Listing of abnormal conjunctival exam results, listing of abnormal slit lamp Lens and slit 
lamp anterior chamber exam results and listing of indirect fundoscopic exam and intra-
ocular pressure results will be provided separately.
Constitutional Symptoms (or B-Symptoms)
A summary of the number and percentage of subjects with any constitutional symptom 
/B-symptom will be displayed by scheduled visits. A summary of improvement, i.e. 
number of subjects who had no symptoms at each post-baseline scheduled visit and had 
at least one at baseline, will also be provided. 
A supporting listing will be provided. 
Organ Examination
The number and percentage of subjects with normal or enlarged organs based on liver 
and spleen examination by palpation/CT scan will be summarized by scheduled visits.
A supporting listing will also be provided. 


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9.
PHARMACOKINETIC ANALYSES
The pharmacokinetic (PK) analyses will be based on the Pharmacokinetic population, 
unless otherwise specified.
Pharmacokinetic data from Part 1 of the study will be analyzed using standard non-
compartmental methods, and combined data from Part 1 and Part 2 of the study will be 
analyzed in a population approach using nonlinear mixed effects modeling. Full details 
are presented in Appendix 12: List of Data Displays. 
9.1.
Endpoint / Variables
9.1.1.
Drug Concentration Measures
Refer to Appendix 5: Data Display Standards & Handling Conventions (Section 16.5.3
Reporting Standards for Pharmacokinetic)
9.1.2.
Derived Pharmacokinetic Parameters
9.1.2.1.
Non-compartmental Analysis

The pharmacokinetic parameters for Part 1 will be calculated by standard non-
compartmental analysis according to current working practices and using Phoenix 
WinNonlin, version 6.3 or later.

All calculations of non-compartmental parameters will be based on actual sampling 
times.

Pharmacokinetic parameters described in Table 7 will be determined from the Cycle 1 
plasma concentration-time data in Part 1 of the study separately for each analyte, as 
data permit.
Table 7
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-)
Area under the concentration-time curve during the dosing interval
AUC(0-∞)
Area under the concentration-time curve extrapolated to infinity will be calculated as: 
AUC = AUC(0-t) + C(t) / lambda_z
%AUCex
The percentage of AUC (0-∞) obtained by extrapolation (%AUCex) will be calculated as:
[AUC(0-inf) – AUC(0-t)] / AUC(0-inf) x 100
Cmax
Maximum observed concentration, determined directly from the concentration-time data 
for each cycle
tmax
Time to reach Cmax, determined directly from the concentration-time data for each cycle
C, 
Ctrough
Trough concentration prior to the next dose for each cycle


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Parameter
Parameter Description
t½
Apparent terminal half-life will be calculated as: 
t½ = ln2 / lambda_z
tlast
Time of last observed quantifiable concentration
CL
Clearance
Vss
Volume of distribution at steady state
z, 
lambda_z
Terminal phase rate constant
Ae(0-24)
Urinary recovery of cys-mcMMAF within the 24-h collection period will be calculated as:
Urine cys-mcMMAF concentration x 24-h urine volume
Fe
Fraction of cys-mcMMAF dose excreted in the 24-h collection period will be calculated as:
Ae(0-24) / cys-mcMMAF dose
9.2.
Population of Interest 
The primary pharmacokinetic analyses will be based on the “Pharmacokinetic” 
population, unless otherwise specified.
9.3.
Statistical Analyses / Methods
Details of the planned displays are provided in Appendix 12: List of Data Displays and 
will be based on GSK Data Standards and statistical principles. Unless otherwise 
specified, endpoints / variables defined in Section 9.1 will be summarised using 
descriptive statistics, graphically presented (where appropriate) and listed.
9.3.1.
Statistical Methodology Specification
The following pharmacokinetic statistical analyses will only be performed if sufficient 
data are available.
9.3.1.1.
Exploratory assessment of dose proportionality:
The PK-dose relationship initially will be examined graphically by plotting AUC(0-∞), 
AUC(0-), and Cmax as a function of the dose levels administered; AUC(0-t) may be 
used for cys-mcMMAF.  Plots of PK parameters versus dose will be produced, with two 
plots for each PK parameter. The first will be on a linear scale, and the second will use 
the logarithmic scale for both axes. 
In practice, at least three dose levels are required to assess dose proportionality. Hence, if 
more than two dose cohorts are required to reach MTD (or recommended dose based on 
available safety, PK, and response data), dose proportionality of GSK2857916, unbound 
antibody, total antibody, and cys-mcMMAF following administration in Cycle 1 will be 
evaluated, if data permit, using the power model.


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Dose Proportionality Analysis
Endpoint(s)

Loge-transformed single dose PK parameters (AUC(0-), AUC(0-), and Cmax; AUC(0-t) for 
cys-mcMMAF) will be investigated.
Model Specification

Endpoints for each analyte will be separately analyzed using appropriate methods for 
GSK2857916 doses. 

Power Model

Dose proportionality of PK parameters AUC(0-), AUC(0-), and Cmax (AUC(0-t) for cys-
mcMMAF) will be assessed following single dose administration of GSK2857916 between 
0.03 mg/kg and 4.6 mg/kg, using the power model as described below:
               y = α * doseβ
               where y denotes the PK parameter being analyzed and α depends on subject.  

Dose proportionality implies that β=1 and will be assessed by estimating β along with its 
90% confidence interval. The exponent, β, in the power model will be estimated by 
regressing the loge-transformed PK parameter on loge-transformed dose.

The power model will be fitted by restricted maximum likelihood (REML) using SAS Proc 
Mixed. A power model with only subject as a random effect power model will be fitted. The 
mean slope will be estimated from the power model and the corresponding 90% 
confidence interval calculated. 

If the 90% confidence interval for the slope regressing dose against exposure is contained
within the interval (0.8, 1.25), the exposure will be considered to be dose proportional.
Model Checking & Diagnostics

Refer to Section 9.3.2.
Model Results Presentation

Power Model

The mean slope and the corresponding 90% confidence interval for each parameter will be 
produced in tabular format. 

Comparative plots of individual PK parameters will be generated by treatment on linear 
and semi-logarithmic scales.

Supportive SAS output from statistical analysis will be generated.
9.3.1.2.
Assessment of Accumulation Ratio:  
To assess the extent of accumulation following GSK2857916 repeat dosing, the observed 
accumulation ratio (Ro) for GSK2857916, total antibody, unbound antibody, and cys-
mcMMAF will be determined as ratio of Cmax and Ctrough at steady-state to Cmax and 
Ctrough after the first dose, respectively, adjusted for any change in GSK2857916 dose.
Ro (Cmax) = Cmax CxD1/Cmax C1D1;
x = 3, 5; 
Ro (Ctrough) = Ctrough CxD1/Ctrough C1D1;
x = 3, 5;
Preliminary pharmacokinetic data indicate that the pharmacokinetics for the third 
consecutive dose given at the planned interval will be at steady state.  Therefore, based 


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on the study design, subjects who meet one of the following criteria will be at steady 
state:

Subjects who receive the same dose without delay or change for Cycles 1, 2, and 3 
(i.e., with dosing delays of ≤3 days).  In this case, Cycle 3 represents steady state.  
Accumulation ratios are calculated as Cycle 3/Cycle 1.  

Subjects who receive the same dose without delay or change to Cycle 5.  
Accumulation ratio = Cycle 5/Cycle1.

Subjects who have a dose reduction or two by Cycle 3, but then dose is maintained at 
the same level and interval through Cycle 5.  Cycle 5 represents steady-state 
pharmacokinetics, but dose adjustment is needed.  Dose adjustment:  multiply 
Cmax/Ctrough values by the ratio (starting dose level/Cycle 3-5 dose level).  
Accumulation ratio = adjusted Cycle 5/Cycle 1.
For the purpose of accumulation ratio analysis, Cmax is defined as the EOI concentration 
at each cycle. 
Exploratory analysis might be performed considering the effect of dose delay on the ratio. 
Accumulation Ratio Assessment (Part 1 and Part 2)
Endpoint(s)

Accumulation ratio (Ro).
The observed accumulation ratio (Ro) will be calculated for each analyte by determining the 
ratio of Cmax at steady state to Cmax on Day 1 (Ro(Cmax)) and the ratio of Ctrough at steady 
state to Ctrough on Day 1 (Ro(Ctrough)).
Model Specification

A mixed effect model will be fitted for each parameter by  actual dose at each cycle as fixed 
effect and subject as random effect. The model will be adjusted by actual dose and dose delay 
status in each cycle. The ratio will be calculated by back-transforming the difference between 
the Least Squares means. Using the pooled estimate of variance, 90% confidence intervals will 
be calculated for the difference and then back-transformed.

The Kenward & Roger degrees of freedom approach will be used.
Model Checking & Diagnostics

Refer to Section 9.3.2.
Model Results Presentation

Geometric least-squares means for each treatment, point estimates and associated 90% 
confidence intervals for the ratios for each parameter will be produced in tabular format. 

Plots of mean Accumulation Ratio will be generated by dose group on linear and semi-
logarithmic scales.  

The accumulation ratio will be listed and summarized along with other PK parameters.

Supportive SAS output from statistical analysis will be generated.
9.3.1.3.
Assessment of Analyte Ratios: 
Following natural log-transformation, Cmax and Ctau of ADC, unbound and total 
antibody, and cys-mcMMAF will be analysed using a mixed effects model with fixed 
effect terms for treatment, visit, and log(body weight). Subject will be treated as a 


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random effect in the model. Point estimates and their associated 90% confidence intervals 
will be constructed for the differences of Cmax and Ctau in analytes and comparison with 
cys-mcMMAF at each cycle. The point estimates and their associated 90% confidence 
intervals then will be back-transformed to provide point estimates and 90% confidence 
intervals for the ratios of analytes to cys-mcMMAF at each cycle. 
Ratio of analytes at each cycle versus cys-mcMMAF at Cycle X:
Ra (Cmax) = Cmax (ADC, unbound anti-body, total anti-body) Cycle X / 
                      Cmax (cys-mcMMAF) Cycle X
X = 1, 2, 3, 5;
Ra (Ctrough) = Ctrough (ADC, unbound anti-body, total anti-body) Cycle X / 
                          Ctrough (cys-mcMMAF) Cycle X
X = 1, 2, 3, 5;
For the purpose of analyte ratio analysis, Cmax is defined as the EOI concentration at 
each cycle, and Ctrough is defined as the concentration immediately prior to the next 
cycle dose.
To fit into the analysis model, the units of the analytes need to be converted from ng/mL 
or pg/mL to nM as below. 
Original unit
Operation
Converted unit
ADC
ng/mL
/152.1
nM
Total Antibody
ng/mL
/152.1
nM
Unbound Antibody
ng/mL
/152.1
nM
cys-mcMMAF
pg/mL
/1045
nM
Pharmacokinetic Statistical Analyses
Endpoint(s)

Cmax, Ctau by analyte and cycle
Model Specification

Repeated measures mixed effects analysis
Model Checking & Diagnostics

Refer to Section 9.3.2
Model Results Presentation

Graphical ratios at Cycle 1

Graphical ratio of analyte to cys-mcMMAF by cycle 


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9.3.2.
Model Checking & Diagnostics
Endpoint(s)

For Dose Proportionality Analysis (Parts 1), Loge-transformed single dose PK 
parameters (AUC(0-), AUC(0-), and Cmax; AUC(0-t) for cys-mcMMAF) in 
Cycle 1, as applicable.

For Accumulation Ratio Assessment (Part 1 and Part 2), Loge-transformed 
accumulation ratio (Ro) for Cmax at steady state to Cmax on Day 1 (Ro(Cmax)) 
and the ratio of Ctrough after the dose at steady state to Ctrough after the dose 
on Day 1 (Ro(Ctrough)).

For Analyte Ratio Assessment (Part 1 and Part 2), Loge-transformed Cmax and 
Ctau
Analysis

Mixed Effects
Assumptions:

Model assumptions will be applied, but appropriate adjustments may be made based on the 
data.

The Kenward and Roger method for approximating the denominator degrees of freedom and 
correcting for bias in the estimated variance-covariance of the fixed effects will be used.

An unstructured covariance structure for the G matrix will be used by specifying ‘type=UN’ on 
the RANDOM line.
o
In the event that this model fails to converge, alternative correlation structures may be 
considered such as VC or CS. 
o
Akaike's Information Criteria (AIC) will be used to assist with the selection of covariance 
structure.

Distributional assumptions underlying the model used for analysis will be examined by 
obtaining a normal probability plot of the residuals and a plot of the residuals versus the fitted 
values (i.e., checking the normality assumption and constant variance assumption of the model 
respectively) to gain confidence that the model assumptions are reasonable. 

If there are any departures from the distributional assumptions, alternative models will be 
explored using appropriate transformed data.


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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.  The influence of subject demographics, baseline characteristics 
including disease activity, and other covariates on the pharmacokinetics of GSK2857916 
will be investigated.  The individual subject pharmacokinetic parameters will be 
estimated and documented for the purposes of any subsequent exposure-response 
(PK/PD) analyses. This analysis will be performed by CPMS and reported separately. 
A summary of the planned population pharmacokinetic analyses is outlined below:

Plasma concentration-time data for GSK2857916 ADC will be subjected to 
nonlinear mixed effects modelling using the program NONMEM to develop a 
population pharmacokinetic model. A similar approach may be used on the data from 
the three analytes (ADC, total antibody, and cys-mcMMAF) together.  

Individual post hoc estimated pharmacokinetic parameters will be summarized 
descriptively.

To support this analysis, a population PK dataset will be generated. The details for 
the dataset specifications are provided in Appendix 9: Population Pharmacokinetic 
(PopPK) Analyses.
Detailed population PK methodology is presented in Appendix 9: Population 
Pharmacokinetic (PopPK) Analyses.


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11.
PHARMACODYNAMIC (AND / OR BIOMARKER)
ANALYSES
The pharmacodynamic analyses will be documented in a separate RAP.


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12.
PHARMACOKINETIC / PHARMACODYNAMIC
ANALYSES
12.1.
Exposure-Response for Efficacy and Corneal Events
The primary goal of this analysis is to characterize the 
pharmacokinetic/pharmacodynamic relationships for GSK2857916 administered IV in 
subjects with multiple myeloma for efficacy and corneal toxicity.  In these analyses, drug 
plasma concentration (or pharmacokinetic parameter) data and pharmacodynamic data 
will be subjected to nonlinear mixed effects modelling using suitable software.  The 
influence of subject demographics and baseline characteristics, including disease activity, 
in this population may be investigated. Detailed PK/PD methodology is provided in 
Appendix 10:  Pharmacokinetic / Pharmacodynamic Analyses.  This analysis will be 
performed by CPMS and reported separately. Concentration-QTc Analyses.
12.2.
Concentration-QTc Analyses
For each ECG assessment, the individual subject’s QTcF change from baseline will be 
calculated and will be merged with time-matched PK concentration values for the 
timepoints at which they are available. QTcF change from baseline (y-axis) will be 
plotted against the PK concentration data (x-axis) separately for each analyte (ADC, 
unbound mAb, total mAb, and cys-mc-MMAF).  If appropriate, linear regression 
analyses may be performed for each analyte-QTcF plot.


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13.
HEALTH OUTCOMES ANALYSES
Symptom impact and HRQoL will be assessed using the e-Diary. The Pain (average and 
worst) and Fatigue (worst) items will be scored as individual items. Baseline will be 
calculated for each item as the mean of all of the assessments captured in the period prior 
to Cycle 1 Day 1 (treatment start date) (patients can only start the diary 2 to 4 days prior 
to Cycle 1 Day 1). There will be no minimum number of data points required to calculate 
a baseline, if only one day has been completed in this time period then this will be used 
as Baseline value. 
Scores will be created for each pain (bone pain worst, bone pain average) and fatigue 
item (worst) during the treatment cycle. The mean for each item will be calculated from 
the available data for assessments on Day 1 through to Day 8 in each cycle (for a score to 
be calculated, at least 4 of the 8 days must be completed, otherwise data to be set to 
missing). For the assessment at Day 15 the stand-alone value will be the score for that 
item for that day. If not completed, then data for Day 15 is set to missing. Change from 
baseline for all pain and fatigue items will be assessed at each cycle. Change will be 
calculated for both time points (Day 1-Day 8 average and Day 15).
Visual Functioning Questionnaires (NEI VFQ-25 and OSDI): Data will be collected from 
end of treatment (EOT) visit as baseline. Additional data will be collected in follow-up 
visits on a monthly basis for subjects with ongoing corneal events or signs at EOT for 1 
year or until resolution, whichever occurs first. These data will not be collected for 
subjects who already completed the treatment. Due to limited number of on-treatment 
subjects at the time of protocol amendment, only individual subject data will be listed.
Data for both measures will be scored as outlined in the User Manuals. 
For the NEI VFQ-25 data will be presented for the overall composite score and the 11 
vison-targeted sub-scores: global vision rating, difficulty with near vision activities; 
difficulty with distance vision activities; limitations in social functioning due to vision; 
role limitations due to vision; dependency on others due to vision; mental health 
symptoms due to vision; driving difficulties; limitations with peripheral vision, 
limitations with color vision; and corneal pain. Items that are left blank (missing data) are 
not taken into account when calculating the scale scores. Sub-scales with at least one item 
answered can be used to generate a sub-scale score. Hence scores represent the average 
for all items in the sub-scale that the respondent answered. Only individual subject data 
will be listed.
For the OSDI, the total score will be calculated as well as scores for the subscales (ocular 
symptom, visual related function and environmental triggers). The total OSDI score 
= ([sum of scores for all questions answered × 100]/[total number of questions answered 
× 4]). Subscale scores are computed similarly with only the questions from each subscale
used to generate its own score. Only individual subject data will be listed.


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14.
ANTI-DRUG ANTIBODY ANALYSES
For each subject, the results and titers of anti-GSK2857916 binding antibodies, and also 
ADC and total antibody concentration will be listed for each assessment time point. The 
frequency and percentage of subjects with positive and negative results will be 
summarized for each assessment time and overall for each subject by dose cohort. The 
conclusive results will be based on the total antibody concentration.


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15.
REFERENCES
Ahn EA, Karlsson MO, Dunne A, et al. Likelihood based approaches to handling data 
below the quantification limit using NONMEM VI. J. Pharmacokinet. Pharmacodyn. 
2008; 35:401-21.
Beal SL. Ways to fit a model with some data below the quantification limit. J. 
Pharmacokinet. Pharmacodyn. 2001; 28:481-504.
Brookmeyer R, Crowley J. A confidence interval for the median survival time. 
Biometrics. 1982 Mar 1:29-41.
GlaxoSmithKline Document Number 2012N155299_05, Study ID: BMA117159. A 
Phase I Open-label, Dose Escalation Study to Investigate the Safety, Pharmacokinetics, 
Pharmacodynamics, Immunogenicity and Clinical Activity of the Antibody Drug 
Conjugate GSK2857916 in Subjects with Relapsed/Refractory Multiple Myeloma and 
Other Advanced Hematologic Malignancies Expressing BCMA. 2017
Hing JP, Woolfrey SG, Greenslade D, Wright PMC. Analysis of toxicokinetic data using 
NONMEM: impact of quantification limit and replacement strategies for censored data. J. 
Pharmacokinet. Pharmacodyn.  2001; 28:465-79.
Hume R. Prediction of lean body mass from height and weight. Journal of clinical 
pathology. 1966 Jul 1;19(4):389-91.
Lee J, Liu D. A predictive probability design for phase II cancer clinical trials. Clinical 
Trials 2008;5:93-106.
Neuenschwander B, Branson M, Gsponer T. Critical aspects of the Bayesian approach to 
phase I cancer trials. Stat Med. 2008 Jun 15; 27(13):2420-39.


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16.
APPENDICES
16.1.
Appendix 1: Protocol Deviation Management and Definitions 
for Per Protocol Population
This study does not have per protocol population.


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16.2.
Appendix 2: Schedule of Activities
16.2.1.
Protocol Defined Schedule of Events
Please see Section 7.1 of Protocol (Version: GSK Document Number 2012N155299_05). 
Weekly Dosing Schedule (Dose Escalation) for Multiple Myeloma and Dose Expansion 
Weekly Dosing Schedule for Multiple Myeloma were not explored in this study.
Weekly dosing schedule was not explored.


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16.2.2.
Dose Escalation
16.2.2.1.
Every 3 Weeks Dosing Schedule for Multiple Myeloma
Time and Events Table for Full Study (Cycle = 21 days)
Study Assessments1
Screen2
Day 1 
C1
Day 2 
C1
Day 8 
C1
Day 15 
C1
Day 1 
C2
D1 of C3-C16
End of Study 
Treatment 
3-Month 
Off-study 
Follow-up
Informed Consent
X
Baseline Demographics
X
Medical History
X
Physical Exam
X
X
X
At the start of each cycle
X
Ocular Exam
X3
X4
At the start of each cycle4
X4
ECOG Performance Status
X
X
At the start of each cycle
X
Vital Signs (BP, HR, Body 
Temperature)
X
X5
X
X
X5
At the start of each cycle5
X
Weight and Height
X
Weight 
only
Weight 
only
Weight only - At the start of each cycle
Weight only
Hematology
X
X6
X
X
X
At the start of each cycle
X
Clinical chemistry
X
X6
X
X
X
X
At the start of each cycle
X
Urine Dipstick
X
X6
X
At the start of each cycle
X
INR, PTT 
X
X6
X
X
X
At the start of each cycle
HBV/HCV tests
X
CK-MB, Troponin 
X7
X7
X7
At the start of each cycle7
X7
BNP
X8
UPEP and urine 
Immunofixation
X
X
At the start of each cycle
SPEP and serum 
Immunofixation, Serum M-
protein Calculation
X
X
At the start of each cycle
Kappa, lambda free LC, FLC 
ratio
X
X
At the start of each cycle
24 hr urine protein and 
albumin
X
X
At the start of each cycle


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Time and Events Table for Full Study (Cycle = 21 days)
Study Assessments1
Screen2
Day 1 
C1
Day 2 
C1
Day 8 
C1
Day 15 
C1
Day 1 
C2
D1 of C3-C16
End of Study 
Treatment 
3-Month 
Off-study 
Follow-up
IgG, IgM, IgA
X
X
At the start of each cycle
CRP, beta2 microglobulin
X
X
At the start of each cycle
Pregnancy Test 
X9
At the start of cycles 59, 99, 139
X9
X10
Chest X-ray
X
12-lead ECG
X11
X11
X11
X11
X11
At the start of each cycle11
X11
LVEF and valves assessment 
(ECHO)
X12
At the start of cycles 412, 912
X12
Extramedullary plasmacytoma 
imaging 
X13
At the start of cycles 513, 913, 1313
X13
BM Aspirate (see below for each test required within procedure):
Disease assessment 
X14
At the time of Complete Response
BCMA assessment and 
PD (flow) 
X15
X15
FISH testing 
X16
BM biopsy for disease 
assessment and BCMA 
expression (IHC) 
X17
At the time of CR
(disease assessment only)
Serum (soluble BCMA)
X18
X18
X18
X18
X18
Predose at the start of each cycle
X18
Serum (cytokines/chemokines)
X19
X
X19
At predose and EOI on D1 of each cycle
X
Serum (anti-drug-antibodies)
X
X20
At the start of cycles 320, 620, 920, 1220 and 
1620
X
Plasma-cfDNA 
X
X 
Peripheral blood (flow for 
TBNK)
X15
X15
At the start of each cycle15
X15
Serial Pharmacokinetics 
(blood)
X21
X21
X21
X21
X21
C3D1 only21
X22
Urine PK
X23
X23
Day 1 of cycles 423, 723, 1023, 1323, 1623
Premedication if needed
X
X
At the start of each cycle
GSK2857916  administration
X24
X24
X24
Steroid eye drops
X25
X25
X25
Adverse Events
Continuous


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Time and Events Table for Full Study (Cycle = 21 days)
Study Assessments1
Screen2
Day 1 
C1
Day 2 
C1
Day 8 
C1
Day 15 
C1
Day 1 
C2
D1 of C3-C16
End of Study 
Treatment 
3-Month 
Off-study 
Follow-up
Concomitant Medications
X
Continuous
Survival Status
X26
Subsequent Treatment
X26
1.
Assessments scheduled on days of dosing should be done prior to drug administration, unless otherwise specified.  All other assessments can be 3 days of scheduled 
occurrence unless otherwise specified.
2.
All Screening assessments must be performed within 14 days prior to first dose unless otherwise specified. Informed Consent must be signed before any study-specific 
assessments are performed.
3.
Screening examination to include BCVA (best-corrected visual acuity), slit lamp examination (with special focus on cornea), intraocular pressure, and dilated fundoscopic 
examination may be performed within 21 days prior to first dose.
4.
On-study exams to include BCVA (best-corrected visual acuity) and slit lamp examination (with special focus on cornea); window for exams is up to 3 days prior to dosing.
5.
On initial (first infusion) dosing day, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +10 minutes and +30 minutes (5 min)  after SOI, EOI, and 1 
hour post EOI.  On subsequent dosing days, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +30 minutes after SOI, and EOI.  The Sentinel Subject 
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.
6.
If completed within 72 hrs prior to the first dose, this assessment need not be repeated on Day 1 of Cycle 1. Refer to Table 15 of the protocol for comprehensive list of lab 
tests.  
7.
Troponin will be measured at the local lab (troponin I or T) and a central lab (troponin I).  CK-MB at the local lab or if not possible by a central laboratory.
8.
BNP to be measured locally, or if not available by a central laboratory, at screening; if cardiac workup is required due to safety concerns during the study, BNP should be 
measured.  
9.
Perform only in women of child-bearing potential.  A serum pregnancy test should be performed at screening, and subsequent pregnancy tests may be either serum or urine; 
10. Final pregnancy test (serum or urine) must be performed in women of childbearing potential 60 days after last study treatment.
11. On dosing days, ECG to be performed in triplicate at predose (within 30 minutes prior to SOI) and EOI.  On days where ECG timepoints align with PK sampling 
timepoints, ECGs should be performed prior to PK samples being drawn (PK sample should be taken at the exact nominal time; refer to footnote 21).  At 
screening, on interim visits (C1D8 and C1D15) and End of Study obtain a single ECG measurement.
12. At Screening, LVEF may be performed within 30 days prior to first dose. All ECHOs indicated on dosing days may be performed up to 5 days before dosing. All ECHOs to be 
done locally and sent to GSK for central imaging storage.
13. May be performed up to 21 days prior to C1D1 as screening value. Needs to be performed by the same method throughout the study as was done at baseline (i.e. if PET 
scan was used as baseline, subject needs to be followed by PET scans).  Selected target lesion needs to be measured and followed over time.
14. Samples from within 14 days prior to first dose are acceptable.
15. Sample(s) collected for analysis by central lab.  The same sample will be used for BCMA (flow) and PD during Screening. On D8 only postdose PD assessment will be 
performed


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64
16. 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.
17. Archival tissue from up to 60 days prior to study is acceptable 
18. A single sample for sBCMA will be collected at C1D8, C1D15 and at the End of Study visit. sBCMA samples will also be collected on  C1D1 at predose (within 30 minutes 
prior to SOI), at EOI (5 minutes) and on C1D2 24h post SOI.  On C2D1 sBCMA will be collected pre-dose (within 30 minutes prior to SOI) and at the EOI (5 minutes)
19. Collect cytokines at predose (within 30 minutes prior to SOI) and EOI (5 min) (even when infusion is interrupted or halted) to assess allergic reaction)
20. All ADA samples will be collected prior to each infusion
21. PK samples to be taken (in all subjects) for both GSK2857916 and cys-mcMMAF measurement: C1D1 at pre-dose (within 30 minutes prior to SOI), 0.5 h after the start of the 
infusion (SOI) (5 min), at the end of infusion (EOI) just before EOI), 1 h after EOI, 3 h after EOI (5 min), 8 h after EOI (15 min), 24h after EOI (1h) (Day 2); C1D8 1 
sample; C1D15 1 sample; C2D1, at pre-dose (within 30 minutes prior to SOI) and at the EOI (just before EOI); C3D1 at pre-dose (within 30 minutes prior to SOI) and at the 
EOI (just before EOI).
22. Collect 1 PK sample at each subject’s final visit. 
23. Pre-specified amounts of urine will be collected for PK analysis from the 24 hour urine collection at Screening, C2D1, C4D1, C7D1, C10D1, C13D1, and C16D1.  Refer to 
Section 7.4.2 of the protocol for details.
24. Study drug administration 3 day window only
25. Prophylaxis with prednisolone phosphate 1% or dexamethasone 0.1% 1 drop QID x 4 days starting 1 day prior to treatment
26. Record subject’s survival status and whether subsequent treatment for disease was given.  Subject does not need to come in for visit.
Abbreviations:
ADA = Antibody Drug Antibody; ALP = alkaline phosphatase; BCVA = best corrected visual acuity; BNP = B-type natriuretic peptide; C1D1 = Cycle 1 Day 1, etc.; cfDNA = 
Circulating free DNA; CK = creatinine kinase;  CRP = C-reactive protein; EM = extramedullary;  EOI = End of Infusion; FLC = free light chain; PD = Pharmacodynamics; PK = 
Pharmacokinetics; QID = 4 times a day; SOI = start of infusion; SPEP = serum protein electrophoresis; UPEP = urine protein electrophoresis


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16.2.2.2.
Weekly Dosing Schedule (Dose Escalation) for Multiple Myeloma
Time and Events Table for Full Study (Cycle = 28 days)
Study Assessments1
Screen2
Day 1 
C1
Day 2 
C1
Day 8 
C1
Day 15 
C1
Day 1 
C2
D1 of C3-C16
End of Study 
Treatment
3-Month Off-
study 
Follow-up
Informed Consent
X
Baseline Demographics
X
Medical History
X
Physical Exam
X
X
X
At the start of each cycle
X
Ocular Exam
X3
X4
At the start of each cycle4
X4
ECOG Performance Status
X
X
At the start of each cycle
X
Vital Signs (BP, HR, Body 
Temperature)
X
X5
X
X
X5
At the start of each cycle5
X
Weight and Height
X
Weight 
only
Weight 
only
Weight only - At the start of each cycle
Weight only
Hematology
X
X6
X
X
X
At the start of each cycle
X
Clinical Chemistry
X
X6
X
X
X
X
At the start of each cycle
X
Urine Dipstick
X
X6
X
At the start of each cycle
X
INR, PTT
X
X6
X
X
X
At the start of each cycle
HBV/HCV tests
X
CK-MB , Troponin 
X7
X7
X7
At the start of each cycle7
X7
BNP
X8
UPEP and urine 
Immunofixation
X
X
At the start of each cycle
SPEP and serum 
Immunofixation and Serum-
M protein Calculation
X
X
At the start of each cycle
Kappa, lambda free LC, 
FLC ratio
X
X
At the start of each cycle
24 hr urine protein and 
albumin
X
X
At the start of each cycle
IgG, IgM, IgA
X
X
At the start of each cycle
CRP, beta2 microglobulin
X
X
X
At the start of each cycle


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Time and Events Table for Full Study (Cycle = 28 days)
Study Assessments1
Screen2
Day 1 
C1
Day 2 
C1
Day 8 
C1
Day 15 
C1
Day 1 
C2
D1 of C3-C16
End of Study 
Treatment
3-Month Off-
study 
Follow-up
Pregnancy Test 
X9
At the start of cycles 59, 99, 139
X9
X10
Chest X-ray
X
12-lead ECG
X11
X11
X11
X11
X11
At the start of each cycle11
X11
LVEF and valves 
assessment (ECHO)
X12
At the start of cycles 412, 912
X12
Extramedullary 
Plasmacytoma Imaging
X13
At the start of cycles 513, 913, 1313
X13
BM Aspirate (see below for each test required within procedure):
Disease assessment 
X14
At the time of Complete Response
BCMA assessment and 
PD (flow) 
X15
X15, 17
FISH testing 
X16
BM biopsy for disease 
assessment 
X18
At the time of Complete Response 
(disease assessment only)
Serum (soluble BCMA)
X19
X19
X19
X19
X19
Predose at the start of each cycle
X
Serum 
(cytokines/chemokines)
X20
X
X20
X20
X20
At predose and EOI on D1 of each cycle
X
Serum (anti-drug-
antibodies)
X21
X21
X21
At the start of cycles 321, 621, 921, 1221 and 
1621
X
Plasma-cfDNA
X
X
Peripheral blood (flow for 
TBNK and intracellular 
cytokine testing)
X15
X15
X15
At the start of each cycle15
X15
Serial Pharmacokinetics 
(blood)
X22
X22
X22
X22
X22
C3D1 only22
X23
Urine PK
X24
X24
Day 1 of cycles 424, 724, 1024, 1324, 1624
Premedication if needed
X
X
X
X
Each dosing week
GSK2857916 
administration
X25
X25
X25
X25
Each dosing week25
Steroid eye drops
X26
X26
X26
X26
Each dosing week26
Adverse Events
Continuous


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Time and Events Table for Full Study (Cycle = 28 days)
Study Assessments1
Screen2
Day 1 
C1
Day 2 
C1
Day 8 
C1
Day 15 
C1
Day 1 
C2
D1 of C3-C16
End of Study 
Treatment
3-Month Off-
study 
Follow-up
Concomitant Medications
X
Continuous
Survival Status
X27
Subsequent Treatment
X27
1.
Assessments scheduled on days of dosing should be done prior to drug administration, unless otherwise specified.  All other assessments can be done 3 days unless otherwise 
specified.
2.
All Screening assessments must be performed within 14 days prior to first dose unless otherwise specified.  Informed Consent must be signed before any study-specific 
assessments are performed.
3.
Screening examination to include BCVA (best-corrected visual acuity), slit lamp examination (with special focus on cornea), intraocular pressure, dilated fundoscopic examination 
may be performed within 21 days prior to first dose
4.
On-study exams, to include BCVA (best-corrected visual acuity) and slit lamp examination (with special focus on cornea); window for exams is up to 3 days prior to dosing.
5.
On initial (first infusion) dosing day, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +10 minutes and +30 minutes (5 min) after SOI, EOI, and 1 hour 
post EOI.  On subsequent dosing days, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +30 minutes after SOI, and EOI.  On days where vital sign 
time points align with PK sampling timepoints, vital signs should be assessed prior to PK samples being drawn.  
6.
If completed within 72 hours prior to first dose, this assessment need not be repeated on Day 1 of Cycle 1.  Refer to Table 15 of the protocol for comprehensive list of lab tests.
7.
Troponin will be measured at the local (troponin I or T) and central (troponin I) lab.  CK-MB at the local lab or if not available by a central laboratory. 
8.
BNP to be measured locally, or if not available by a central laboratory, at screening; if cardiac workup is required due to safety concerns during the study, BNP should be 
measured.
9.
Perform only in women of child-bearing potential.  A serum pregnancy test should be performed at screening, and subsequent pregnancy tests may be either serum or urine.  
10. Final pregnancy test (serum or urine) must be performed in women of childbearing potential 60 days after last study treatment.
11. On dosing days, ECG to be performed in triplicate at predose (within 30 minutes prior to SOI) and EOI.  On days where ECG timepoints align with PK sampling timepoints, 
ECGs should be performed prior to PK samples being drawn (PK sample should be taken at the exact nominal time; refer to footnote 22).  At screening and at End of Study, 
obtain a single ECG measurement.
12. At Screening, LVEF may be performed within 30 days prior to first dose; All ECHOs indicated on dosing days may be performed up to 5 days before dosing.  ECHOs to be done 
locally and sent to GSK for central imaging storage.
13. May be performed up to 21 days prior to C1D1 as screening value.  Needs to be performed by the same method throughout the study as was done at baseline (i.e. if PET scan 
was used as baseline, subject needs to be followed by PET scans).  Selected target lesion needs to be measured and followed over time.
14. Samples from within 14 days prior to first dose are acceptable.
15. Sample(s) collected for analysis by central lab. The same sample collected on Day 1 of cycle 1 prior to dosing will be used for BCMA (flow) and PD u. 
16. 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.
17. Collect sample prior to dosing.


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68
18. Archival tissue from up to 60 days prior to study is acceptable.
19. A single sample for sBCMA will be collected at C1D8 predose, and at the End of Study visit. sBCMA samples will also  be collected on C1D1 at predose (within 30 minutes prior to 
SOI), at EOI (5 minutes) and on C1D2 24h post SOI. On C1D15 and C2D1 collect at predose (within 30 minutes prior to SOI) and EOI (5 minutes)
20. Collect cytokines at predose (within 30 minutes prior to SOI) and EOI (5 min) (even when infusion is interrupted or halted) to assess allergic reaction
21. All ADA samples will be collected prior to each infusion
22. PK samples to be taken (in all subjects) for both GSK2857916 and cys-mcMMAF measurement: C1D1 at predose (within 30 minutes prior to SOI), 0.5 h after the start of the 
infusion, at EOI (just before EOI), 1 h after EOI (5 min), 3 h after EOI (5 min), 8 h after EOI (15 min), and 24h after EOI (1 h) (Day 2); C1D8 at predose (within 30 minutes 
prior to SOI), and at EOI (just before EOI); C1D15 at predose (within 30 minutes prior to SOI) and at EOI (just before EOI); C2D1 at predose (within 30 minutes prior to SOI), at 
EOI (just before EOI); C3D1 at predose (within 30 minutes prior to SOI) and at EOI (just before EOI).
23. Collect 1 PK sample at each subject’s final visit.
24. Pre-specified amounts of urine will be collected for PK analysis from the 24 hour urine collection at Screening, C2D1, C4D1, C7D1, C10D1, C13D1, and C16D1.  Refer to Section 
7.4.2 of the protocol for details.
25. Study drug administration 1 day window only.
26. Prophylaxis with prednisolone phosphate 1% or dexamethasone 0.1% 1 drop QID x 4 days starting 1 day prior to treatment
27. Record subject’s survival status and whether subsequent treatment for disease was given.  Subject does not need to come in for visit.
Abbreviations:
ADA = Antibody Drug Antibody; ALP = alkaline phosphatase; BCVA = best corrected visual acuity; BNP = B-type natriuretic peptide; C1D1 = Cycle 1 Day 1, etc.; cfDNA = Circulating 
free DNA; CK = creatinine kinase;  CRP = C-reactive protein; EM = extramedullary;  EOI = End of Infusion; FLC = free light chain; PD = Pharmacodynamics; PK = Pharmacokinetics; 
QID = 4 times a day; SOI = start of infusion; SPEP = serum protein electrophoresis; UPEP = urine protein electrophoresis


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16.2.3.
Dose Expansion
16.2.3.1.
Every 3 Weeks Dosing Schedule for Multiple Myeloma
Time and Events Table for Full Study (Cycle = 21 days)
Study Assessments1
Screen2
Day 1 
C1
Day 8 
C1
Day 15 
C1
Day 1 C2
D1 of C3-C16
End of 
Study 
Treatment34
Monthly 
Follow 
up35
Baseline Demographics
X
Medical History
X
Physical Exam
X
X
X
At the start of each cycle
X
Ocular Exam
X3
X4
At the start of each cycle4
X4
X35
ECOG Performance 
Status
X
X
At the start of each cycle
X
Vital Signs (BP, HR, 
Body Temperature)
X
X5
X
X
X5
At the start of each cycle5
X
Weight and Height
X
Weight 
only
Weight only
Weight only - At the start of each 
cycle
Weight only
Hematology
X
X6
X
X
X
At the start of each cycle
X
Clinical chemistry
X
X6
X
X
X
At the start of each cycle
X
Urine Dipstick
X
X6
X
At the start of each cycle
X
INR, PTT
X
X6
X
X
X
At the start of each cycle
HBV/HCV tests
X
CK-MB , Troponin
X7,8
X7,8
X7,8
At the start of each cycle7, 8
X7,8
BNP
X9
UPEP and urine 
Immunofixation
X
X
At the start of each cycle
SPEP and serum 
immunofixation and 
Serum M-protein 
Calculation
X
X
At the start of each cycle
Kappa, lambda free LC, 
FLC ratio
X
X
At the start of each cycle


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Time and Events Table for Full Study (Cycle = 21 days)
Study Assessments1
Screen2
Day 1 
C1
Day 8 
C1
Day 15 
C1
Day 1 C2
D1 of C3-C16
End of 
Study 
Treatment34
Monthly 
Follow 
up35
24 hr urine protein and 
albumin
X
X
At the start of each cycle
IgG, IgM, IgA
X
X
At the start of each cycle
CRP, beta2 
microglobulin
X
X
At the start of each cycle
Pregnancy Test
X10
At the start of cycles 510, 910, 1310
X10
X11
Chest X-ray
X
12-lead ECG
X12
X12
X12
X12
X12
At the start of each cycle12
X12
LVEF and valves 
assessment (ECHO)
X13
At the start of cycles 413, 913
X13
Extramedullary 
Plasmacytoma Imaging
X14
At the start of cycles 514, 914, 1314
X14
BM Aspirate (see below for each test required within procedure):
Disease 
assessment
X15
At the time of Complete Response
BCMA assessment 
and PD (flow)
X16
X16, 18
FISH testing
X17
BM biopsy for disease 
assessment 
X19
At the time of CR (disease 
assessment only)
Serum (soluble BCMA)
X20
X20
Predose at the start of each cycle
X
Serum 
(cytokines/chemokines)
X21
X21
Predose and EOI on D1 of each 
cycle
X
Serum (anti-drug-
antibodies)
X22
X22
At the start of cycles 322, 622, 922, 
1222 and 1622
X
Plasma-cfDNA
X
X
Peripheral blood (flow 
for TBNK and 
intracellular cytokine 
testing)
X23
X
X23
At the start of each cycle23
X23
Sparse PK (blood)
X24
X24
C3D124 and C5D124 only
X25
Genetics sample
X26


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Time and Events Table for Full Study (Cycle = 21 days)
Study Assessments1
Screen2
Day 1 
C1
Day 8 
C1
Day 15 
C1
Day 1 C2
D1 of C3-C16
End of 
Study 
Treatment34
Monthly 
Follow 
up35
Premedication if 
needed
X
X
X
GSK2857916  
administration
X27
X27
X27
Steroid eye drops
X28
X28
X28
Adverse Events
Continuous
Concomitant 
Medications
X
Continuous
e-Diary
X
X
X
X
X30
X30
X
OSDI
X31
X31
NEI-VFQ-25
X31
X31
Exit Interview
X32
Follow-up Interview
X33
Survival Status
X29
Subsequent Treatment
X29
1.
Assessments scheduled on days of dosing should be done prior to drug administration, unless otherwise specified.  All other assessments can be done 3 days unless otherwise 
specified
2.
All Screening assessments must be performed within 14 days prior to first dose unless otherwise specified. Informed Consent must be signed before any study-specific 
assessments are performed.
3.
Screening examination to include BCVA (best-corrected visual acuity), slit lamp examination (with special focus on cornea), intraocular pressure, and dilated fundoscopic 
examination may be performed within 21 days prior to first dose.
4.
On-study exams, to include BCVA (best-corrected visual acuity) and slit lamp examination (with special focus on cornea); window for exams is up to 3 days prior to dosing. In the 
event that a subject has a dose delay due to a non-ocular toxicity and an ocular exam has been performed for that cycle, a repeat ocular exam 3 days prior to dosing may be 
omitted if the participant did not have corneal signs on the previous exam and does not have any new corneal symptoms.
5.
On initial (first infusion) dosing day, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +10 minutes, +30 minutes (15 min) after SOI, EOI, and 1 hour post 
EOI.  On subsequent dosing days, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +30 minutes after SOI, and EOI.  On days where vital sign 
timepoints align with PK sampling timepoints, vital signs should be assessed prior to PK samples being drawn.  
6.
If completed within 72 hrs prior to the first dose, this assessment need not be repeated on Day 1 of Cycle 1.  Refer to Table 15 of the protocol for a comprehensive list of lab tests.  
7.
Troponin will be measured at the local (troponin I or T) and central (troponin I) lab. 
8.
CK-MB at the local lab or if not available by a central laboratory. 
9.
BNP to be measured locally, or if not available by a central laboratory, at screening; if cardiac workup is required due to safety concerns during the study, BNP should be 
measured.


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10. Perform only in women of child-bearing potential.  A serum pregnancy test should be performed at screening, and subsequent pregnancy tests may be either serum or urine.
11. Final pregnancy test (serum or urine) must be performed in women of childbearing potential 60 days after last study treatment.
12. ECGs to be performed in triplicate.  On dosing days, ECG to be performed at predose (within 30 minutes prior to SOI) and EOI.  At screening, on interim visits (C1D8 and C1D15) 
and End of Study, obtain a single ECG measurement. On days where ECG timepoints align with PK sampling timepoints, ECGs should be performed prior to PK samples 
being drawn (PK sample should be taken at the exact nominal time; refer to footnote 24) 
13. At Screening, LVEF may be performed within 30 days prior to first dose. All ECHOs indicated on dosing days may be performed up to 5 days before dosing. ECHOs to be done 
locally and sent to GSK for central imaging storage.
14. May be performed up to 21 days prior to C1D1 as screening value.  Needs to be performed with the same method throughout the study as was done at baseline (i.e. if PET scan 
was used as baseline, subject needs to be followed by PET scans).  Selected target lesion needs to be measured and followed over time.
15. Samples from within 14 days prior to first dose are acceptable.
16. Sample(s) collected for analysis at central lab. The same sample will be used for BCMA (flow) and PD. On D8 only postdose PD assessment will be performed, if applicable (refer 
to footnote 18).
17. 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.
18. Additional samples may be collected in some subjects (up to 6) for further exploration of PD.
19. Archival tissue from up to 60 days prior to study is acceptable.
20. Collect sBCMA at C1D1 predose (within 30 minutes prior to SOI) and at EOI (5 minutes), C2D1 at predose (within 30 minutes prior to SOI) and at EOI (+- 5 minutes).
21. Collect cytokines at predose (within 30 minutes prior to SOI) and EOI (5 min) (even when infusion is interrupted or halted) to assess allergic reaction
22. All ADA samples will be collected prior to each infusion
23. Flow cytometry performed central laboratory.
24. PK samples to be taken for both GSK2587916 and cys-mcMMAF measurement on C1D1, C2D1, C3D1, and C5D1 at predose (within 30 minutes prior to SOI) and at EOI (just 
before EOI).
25. Collect 1 PK sample at each subject’s final visit.
26. Informed consent for optional genetics research should be obtained before collecting a sample.
27. Study drug administration 3 day window only.
28. Prophylaxis with prednisolone phosphate 1% or dexamethasone 0.1% 1 drop QID x 4 days starting 1 day prior to treatment
29. All participants should be followed for survival for 1 year from last subject last dose. and whether subsequent treatment for disease was given.  Subject does not need to come in 
for visit. Participants who have completed treatment or the 3 month follow up visit (end of study) prior to amendment 5 will be reconsented for further follow up and survival status. 
30. e-Diary  to be completed at screening, then Days 1-7, 8, 15 of each treatment cycle. Upon implementation of the e-Diary, these assessments will be required.
31. OSDI and NEI-VFQ-25 to be administered during end of study treatment visit.  Additional assessments for subjects who are experiencing corneal symptoms to be completed via 
telephone on a monthly basis for up to 1 year, or until resolution of symptoms (whichever comes first) during the follow-up period. 
32. Exit interview to be performed within 21 days of end of study visit
33. Optional follow-up telephone interview to explore visual symptoms and changes in symptoms and related impacts following treatment discontinuation be performed at least 6 
months following the End of Study Treatment visit.  This interview would only be for those subjects who experienced corneal symptoms during treatment and consent to 
participate.
34. End of treatment visit should be performed within 30 days (+7 days) after the last dose or prior to the start of new anti-cancer treatment, whichever is earlier. In cases where more 
than 30 days (+7 days) have elapsed from the date of the subject’s last dose due to dosing delays and a subsequent decision to take the subject off treatment, the end of study 
treatment visit should be scheduled as soon as possible to allow the final assessments to be performed at the earliest date.


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35. Participants with corneal signs or symptoms at the end of study treatment visit should be monitored by ophthalmic exam once a  month after the last study dose until deemed 
clinically stable by an eye care professional complete resolution or for 12 months (whichever comes first). Corneal exams to include BCVA and slit lamp examination (with special 
focus on cornea). Participants who have completed treatment or the 3 month follow up visit (end of study) will be reconsented for  additional ophthalmology follow up.
Abbreviations:
ADA = Antibody Drug Antibody; ALP = alkaline phosphatase; BCVA = best corrected visual acuity; BNP = B-type natriuretic peptide; C1D1 = Cycle 1 Day 1, etc.; cfDNA = 
Circulating free DNA; CK = creatinine kinase;  CRP = C-reactive protein; EM = extramedullary;  EOI = End of Infusion; FLC = free light chain; PD = Pharmacodynamics; PK = 
Pharmacokinetics; QID = 4 times a day; SOI = start of infusion; SPEP = serum protein electrophoresis; UPEP = urine protein electrophoresis


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16.2.3.2.
Dose Expansion Weekly Dosing Schedule for Multiple Myeloma
Time and Events Table for Full Study (Cycle = 28 days)
Study Assessments1
Screen2
Day 1 
C1
Day 8 C1
Day 15 
C1
Day 1 
C2
Day 15 
C2
D1 of C3-C16
End of Study 
Treatment
3-Month 
Off-study 
Follow-up
Informed Consent
X
Baseline Demographics
X
Medical History
X
Physical Exam
X
X
X
At the start of each cycle
X
Ocular Exam
X3
X4
At the start of each cycle4
X4
ECOG Performance 
Status
X
X
At the start of each cycle
X
Vital Signs (BP, HR, Body 
Temperature)
X
X5
X5
X5
X5
At the start of each cycle5
X
Weight and Height
X
Weight 
only
Weight 
only
Weight only - At the start of each cycle
Weight
Hematology
X
X6
X
X
X
At the start of each cycle
X
Clinical chemistry
X
X6
X
X
X
X
At the start of each cycle
X
Urine Dipstick
X
X6
X
At the start of each cycle
X
INR, PTT 
X
X6
X
X
X
At the start of each cycle
HBV/HCV tests
X
CK-MB , Troponin 
X7
X7
X7
At the start of each cycle7
X7
BNP
X8
UPEP and urine 
immunofixation
X
X
At the start of each cycle
SPEP and serum 
immunofixation and Serum 
M-protein Calculation
X
X
At the start of each cycle
Kappa, lambda free LC, 
FLC ratio
X
X
At the start of each cycle
24 hr urine protein and 
albumin 
X
X
At the start of each cycle
IgG, IgM, IgA
X
X
At the start of each cycle


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Time and Events Table for Full Study (Cycle = 28 days)
Study Assessments1
Screen2
Day 1 
C1
Day 8 C1
Day 15 
C1
Day 1 
C2
Day 15 
C2
D1 of C3-C16
End of Study 
Treatment
3-Month 
Off-study 
Follow-up
CRP, beta2 microglobulin
X
X
X
At the start of each cycle
Pregnancy Test 
X9
At the start of cycles 59, 99, 139
X9
X10
Chest X-ray
X
12-lead ECG
X11
X11
X11
X11
X11
At the start of each cycle11
X11
LVEF and valves 
assessment (ECHO)
X12
At the start of cycles 412, 912
X12
Extramedullary 
Plasmacytoma Imaging
X13
At the start of cycles 513, 913, 1313
X13
BM Aspirate (see below for each test required within procedure):
Disease assessment 
X14
At the time of Complete Response
BCMA assessment 
and PD (flow)
X15
X15, 17
FISH testing 
X16
BM biopsy for disease 
assessment 
X18
At the time of Complete Response (disease 
assessment only)
Serum (soluble BCMA) 
X19
X19
X19
X19
Predose at the start of each cycle
X
Serum 
(cytokines/chemokines)
X20
X20
X20
X20
Predose and EOI on D1 of each cycle
X
Serum (anti-drug-
antibodies)
X21
X21
X21
At the start of cycles 321, 621, 921, 1221 and 
1621
X
Plasma-cfDNA 
X
X
X 
Peripheral blood (flow for 
TBNK and intracellular 
cytokine testing)
X15
X
X15
At the start of each cycle15
X15
Sparse PK (blood) 
X22
X22
X22
X22
X22
C3D122, C3D1522, and C5D122 only
X23
Genetics sample
X24
Premedication if needed
X
X
X
X
X
Each dosing week
GSK2857916  
administration
X25
X25
X25
X25
X25
Each dosing week25
Steroid eye drops
X26
X26
X26
X26
X26
Each dosing week26
Adverse Events
Continuous


CONFIDENTIAL
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Time and Events Table for Full Study (Cycle = 28 days)
Study Assessments1
Screen2
Day 1 
C1
Day 8 C1
Day 15 
C1
Day 1 
C2
Day 15 
C2
D1 of C3-C16
End of Study 
Treatment
3-Month 
Off-study 
Follow-up
Concomitant Medications
X
Continuous
e-Diary
X
X
X
X
X
X28
X
Exit Interview
X29
Survival Status
X27
Subsequent Treatment
X27
1.
Assessments scheduled on days of dosing should be done prior to drug administration, unless otherwise specified. All other assessments can be done 3 days unless otherwise 
specified 
2.
All Screening assessments must be performed within 14 days prior to first dose unless otherwise specified. Informed Consent must be signed before any study-specific 
assessments are performed.
3.
Screening examination to include BCVA (best-corrected visual acuity), slit lamp examination (with special focus on cornea), intraocular pressure, and dilated fundoscopic 
examination may be performed within 21 days prior to first dose.
4.
On-study exams, to include BCVA (best-corrected visual acuity) and slit lamp examination (with special focus on cornea); window for exams is up to 3 days prior to dosing.
5.
On initial (first infusion) dosing day, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +10 minutes and +30 minutes (5 min) after SOI, EOI, and 1 hour 
post EOI.  On subsequent dosing days, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +30 minutes after SOI, and EOI.  On days where vital sign 
timepoints align with PK sampling timepoints, vital signs should be assessed prior to PK samples being drawn.  
6.
If completed within 72 hrs prior to the first dose, this assessment need not be repeated on Day 1 of Cycle 1.  Refer to Table 15 of the protocol for comprehensive list of lab tests.   
7.
Troponin will be measured at the local (troponin I or T) and central (troponin I) lab.  CK-MB at the local lab, or if not available by a central laboratory. 
8.
BNP to be measured locally, or if not available by a central laboratory, at screening; if cardiac workup is required due to safety concerns during the study, BNP should be 
measured.
9.
Perform only in women of child-bearing potential.  A serum pregnancy test should be performed at screening, and subsequent pregnancy tests may be either serum or urine
10. Final pregnancy test (serum or urine) must be performed in women of childbearing potential 60 days after last study treatment.
11. ECGs to be performed in triplicate.  On dosing days, ECG to be performed at predose (within 30 minutes prior to SOI) and EOI.  On days where ECG timepoints align with PK 
sampling timepoints, ECGs should be performed prior to PK samples being drawn (PK sample should be taken at the exact nominal time; refer to footnote 22). At 
screening and End of Study, obtain a single ECG measurement.
12. At Screening, LVEF may be performed within 30 days prior to first dose.  All ECHOs indicated on dosing days may be performed up to 7 days before dosing. ECHOs to be done 
locally and sent to GSK for central imaging storage.
13. May be performed up to 21 days prior to C1D1 as screening value.  Needs to be performed with the same method throughout the study as was done at baseline (i.e. if PET scan 
was used as baseline, subject needs to be followed by PET scans).  Selected target lesion needs to be measured and followed over time.
14. Samples from within 14 days prior to first dose are acceptable.
15. Sample(s) collected for analysis at central lab. The same sample collected on Day 1 of cycle1 prior to dosing will be used for BCMA (flow) and PD (refer to footnote 17).


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77
16. 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.
17. Additional samples may be collected from 6 subjects in the MM cohort.  Collect sample prior to dosing.
18. Archival tissue from up to 60 days prior to study is acceptable
19. A single sBCMA sample will be collected at C1D1 predose (within 30 minutes prior to SOI) unless otherwise specified.  On C1D15 and C2D1 collect samples at predose (within 30 
minutes prior to SOI) and at EOI (5 minutes).  
20. Collect cytokines at predose (within 30 minutes prior to SOI) and EOI (5 min) (even when infusion is interrupted or halted) to assess allergic reaction
21. All ADA samples will be collected prior to each infusion
22. PK samples to be taken for both GSK2857916 and cys-mcMMAF measurement at C1D1 predose (within 30 minutes prior to SOI), EOI (just before EOI), 1 hour post EOI (5 min), 
and 3 hours post EOI (5 min); predose (within 30 minutes prior to SOI) and EOI (just before EOI) on C1D8, C1D15, C2D1, C2D15, C3D1, C3D15, and C5D1
23. Collect 1 PK sample at each subject’s final visit
24. Informed consent for optional genetics research should be obtained before collecting a sample.
25. Study drug administration 1 day window only
26. Prophylaxis with prednisolone phosphate 1% or dexamethasone 0.1% 1 drop QID x 4 days starting 1 day prior to treatment
27. Record subject’s survival status and whether subsequent treatment for disease was given.  Subject does not need to come in for visit.
28. e-Diary  to be completed at screening, then Days 1-7, 8, 15 of each treatment cycle. Upon implementation of the e-Diary, these assessments will be required.
29. 29.Exit interview to be performed within 14 days of end of study visit
Abbreviations:
ADA = Antibody Drug Antibody; ALP = alkaline phosphatase; BCVA = best corrected visual acuity; BNP = B-type natriuretic peptide; C1D1 = Cycle 1 Day 1, etc.; cfDNA = 
Circulating free DNA; CK = creatinine kinase;  CRP = C-reactive protein; EM = extramedullary;  EOI = End of Infusion; FLC = free light chain; PD = Pharmacodynamics; PK = 
Pharmacokinetics; QID = 4 times a day; SOI = start of infusion; SPEP = serum protein electrophoresis; UPEP = urine protein electrophoresis


CONFIDENTIAL
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16.2.3.3.
Dose Expansion Every 3 Weeks Dosing Schedule for Lymphomas
Study Assessments1
Screen2
Day 1 C1
Day 8 C1
Day 15 C1
Day 1 C2
D1 of C3-C16
End of 
Study 
Treatment26
Monthly 
Follow 
up27
Informed Consent
X
Baseline Demographics
X
Medical History
X
Physical Exam
X
X
X
At the start of each cycle
X
Ocular Exam
X3
X4
At the start of each cycle4
X4
X27
ECOG Performance 
Status
X
X
At the start of each cycle
X
Vital Signs (BP, HR, 
Body Temperature)
X
X5
X
X
X5
At the start of each cycle5
X
Weight and Height
X
Weight only
Weight only
Weight only - At the start of each 
cycle
Weight only
Hematology
X
X6
X
X
X
At the start of each cycle
X
Clinical chemistry
X
X6
X
X
X
At the start of each cycle
X
Urine Dipstick
X
X6
X
At the start of each cycle
X
INR, PTT
X
X6
X
X
X
At the start of each cycle
HBV/HCV tests
X
CK-MB, Troponin 
X7,8
X7,8
X7,8
At the start of each cycle7
X7,8
BNP
X9
24 hr urine protein and 
albumin 
X
X
At the start of each cycle
IgG, IgM, IgA
X
X
At the start of each cycle
CRP, beta2 
microglobulin
X
X
At the start of each cycle
Pregnancy Test 
X10
At the start of cycles 510, 910, 
1310
X10
X11
Chest X-ray
X
12-lead ECG
X12
X12
X12
X12
X12
At the start of each cycle12
X12
LVEF and valves 
assessment (ECHO)
X13
At the start of cycles 413, 913
X13
Serum (soluble BCMA) 
X14
X14


CONFIDENTIAL
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Study Assessments1
Screen2
Day 1 C1
Day 8 C1
Day 15 C1
Day 1 C2
D1 of C3-C16
End of 
Study 
Treatment26
Monthly 
Follow 
up27
Serum 
(cytokines/chemokines)
X15
X15
Predose and EOI on D1 of each 
cycle
X
Serum (anti-drug-
antibodies)
X16
X16
At the start of cycles 316, 616, 916, 
1216 and 1616
X
Plasma-cfDNA 
X
X 
Peripheral blood (flow 
for TBNK and 
intracellular cytokine 
testing)
X17
X17
X17
At the start of each cycle17
X17
Sparse PK (blood)
X18
X18
C3D118 and C5D118
X19
Genetics sample
X20
CT Scan/PET Scan for 
disease assessments 
X21
At the start of cycles 4, 7, 10, 13, 
and 16
Premedication if needed
X
X
At the start of each cycle
GSK2857916  
administration
X22
X22
X22
Steroid eye drops
X23
X23
At the start of each cycle23
Tumor biopsy for BCMA 
expression
X24
Adverse Events
Continuous
Concomitant 
Medications
X
Continuous
Survival Status
X25
Subsequent Treatment
X25
1.
Assessments scheduled on days of dosing should be done prior to drug administration, unless otherwise specified.  All other assessments can be done 3 days of scheduled 
occurrence unless otherwise specified.
2.
All Screening assessments must be performed within 14 days prior to first dose unless otherwise specified. Informed Consent must be signed before any study-specific 
assessments are performed.
3.
Screening examination to include BCVA (best-corrected visual acuity), slit lamp examination (with special focus on cornea), intraocular pressure, and dilated fundoscopic 
examination may be performed within 21 days prior to first dose.
4.
On-study exams to include BCVA (best-corrected visual acuity) and slit lamp examination (with special focus on cornea); window for exams is up to 3 days prior to dosing.  In the 
event that a subject has a dose delay due to a non-ocular toxicity and an ocular exam has been performed for that cycle, a repeat ocular exam 3 days prior to dosing may be 
omitted if the participant did not have corneal signs on the previous exam and does not have any new corneal symptoms. 


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5.
On initial (first infusion) dosing day, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +10 minutes, +30 minutes (±15 min) after SOI, EOI, and 1 hour post 
EOI.  On subsequent dosing days, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +30 minutes after SOI, and EOI.  On days where vital sign 
timepoints align with PK sampling timepoints, vital signs should be assessed prior to PK samples being drawn.  
6.
If completed within 72 hrs prior to the first dose, this assessment need not be repeated on Day 1 of Cycle 1.  Refer to Table 15 of the protocol for a comprehensive list of lab 
tests.  
7.
Troponin will be measured at the local (troponin I or T) and central (troponin I) lab.  
8.
CK-MB at the local lab, or if not available by a central laboratory. 
9.
BNP to be measured locally at screening; if cardiac workup is required due to safety concerns during the study, BNP should be measured.
10. Perform only in women of child-bearing potential.  A serum pregnancy test should be performed at screening, and subsequent pregnancy tests may be either serum or urine.
11. Final pregnancy test (serum or urine) must be performed in women of childbearing potential 60 days after last study treatment.
12. On dosing days, triplicate ECGs to be performed at predose (within 30 minutes prior to SOI) and EOI.  On days where ECG timepoints align with PK sampling timepoints, 
ECGs should be performed prior to PK samples being drawn (PK sample should be taken at the exact nominal time; refer to footnote 18).  At screening, on interim visits 
(C1D8 and C1D15) and End of Study, obtain a single ECG measurement.
13. At Screening, LVEF may be performed within 30 days prior to first dose.  All ECHOs indicated on dosing days may be performed up to 5 days. ECHOs to be done locally and sent 
to GSK for central imaging storage.
14. A single sBCMA sample will be collected at C1D1 predose (within 30 minutes prior to SOI).  On C2D1 sBCMA will be collected at predose (within 30 minutes prior to SOI) and at 
EOI (5 minutes).
15. Collect cytokines at predose (within 30 minutes prior to SOI) and EOI (5 min) (even when infusion is interrupted or halted) to assess allergic reaction.
16. All ADA samples will be collected prior to each infusion.
17. Sample(s) collected for analysis by central lab.
18. PK samples to be taken for both GSK2587916 and cys-mcMMAF measurement on C1D1 at pre-dose (within 30 minutes prior to SOI), at EOI (just before EOI), 1 h after EOI (5 
min), 3 h after EOI (5 min); C2D1, C3D1, and C5D1 at pre-dose (within 30 minutes prior to SOI) and at EOI (just before EOI).
19. Collect 1 PK sample at each subject’s final visit.
20. Informed consent for optional  genetics research should be obtained before collecting a sample.
21. CT/PET or CT scans from within 21 days prior to first dose are acceptable. CT scans are acceptable at all restaging assessments unless CR is suspected, in which case a 
PET/CT scan will be obtained to confirm CR.
22. Study drug administration 3 day window only.
23. Prophylaxis with prednisolone phosphate 1% or dexamethasone 0.1% 1 drops QID x 4 days starting 1 day prior to treatment.
24. Archived or fresh tissue required for BCMA testing.  Refer to Section 5.2.1 of the protocol Inclusion Criterion #4 for eligibility criteria. 
25. Record subject’s survival status until last subject completes or discontinues treatment and whether subsequent treatment for disease was given.  Subject does not need to come 
in for visit.
26. End of treatment visit should be performed within 30 days (+7 days) after the last dose or prior to the start of new anti-cancer treatment, whichever is earlier. In cases where more 
than 30 days (+7 days) have elapsed from the date of the subject’s last dose due to dosing delays and a subsequent decision to take the subject off treatment, the end of study 
treatment visit should be scheduled as soon as possible to allow the final assessments to be performed at the earliest date.
27. All participants should be followed for survival for 1 year from last dose. Participants with corneal signs or symptoms at the end of study treatment visit should be monitored by
ophthalmic exam every month after the last study dose until deemed clinically stable by an eye care professional or for 12 months (whichever comes first). Corneal exams to 
include BCVA and slit lamp examination (with special focus on cornea).


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Abbreviations:
ADA = Antibody Drug Antibody; ALP = alkaline phosphatase; BCVA = best corrected visual acuity; BNP = B-type natriuretic peptide; C1D1 = Cycle 1 Day 1, etc.; cfDNA = 
Circulating free DNA; CK = creatine kinase; CRP = C-reactive protein; EOI = End of Infusion; PD = Pharmacodynamics; PK = Pharmacokinetics; QID = 4 times a day; SOI = start 
of infusion


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16.2.3.4.
Dose Expansion Weekly Dosing Schedule for Lymphomas
Time and Events Table for Full Study (Cycle = 28 days)
Study Assessments1
Screen2
Day 1 
C1
Day 8 C1
Day 15 
C1
Day 1 
C2
Day 15 
C2
D1 of C3-C16
End of Study 
Treatment
3-Month 
Off-study 
Follow-up
Informed Consent
X
Baseline Demographics
X
Medical History
X
Physical Exam
X
X
X
At the start of each cycle
X
Ocular Exam
X3
X4
At the start of each cycle4
X4
ECOG Performance 
Status
X
X
At the start of each cycle
X
Vital Signs (BP, HR, Body 
Temperature)
X
X5
X5
X5
X5
At the start of each cycle5
X
Weight and Height
X
Weight 
only
Weight 
only
Weight only - At the start of each cycle
Weight
Hematology
X
X6
X
X
X
At the start of each cycle
X
Clinical chemistry
X
X6
X
X
X
X
At the start of each cycle
X
Urine Dipstick
X
X6
X
At the start of each cycle
X
INR, PTT 
X
X6
X
X
X
At the start of each cycle
HBV/HCV tests
X
CK-MB , Troponin 
X7
X7
X7
At the start of each cycle7
X7
BNP
X8
24 hr urine protein and 
albumin 
X
X
At the start of each cycle
IgG, IgM, IgA
X
X
At the start of every other  cycle
CRP, beta2 microglobulin
X
X
At the start of each cycle
Pregnancy Test 
X9
At the start of cycles 59, 99, 139
X9
X10
Chest X-ray
X
12-lead ECG
X11
X11
X11
X11
X11
At the start of each cycle11
X11
LVEF and valves 
assessment (ECHO)
X12
At the start of cycles 412, 912
X12


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Time and Events Table for Full Study (Cycle = 28 days)
Study Assessments1
Screen2
Day 1 
C1
Day 8 C1
Day 15 
C1
Day 1 
C2
Day 15 
C2
D1 of C3-C16
End of Study 
Treatment
3-Month 
Off-study 
Follow-up
Serum (soluble BCMA) 
X13
X13
X13
X13
X13
Serum 
(cytokines/chemokines)
X14
X14
X14
X14
Predose and EOI on D1 of each cycle
X
Serum (anti-drug-
antibodies)
X15
X15
X15
At the start of cycles 315, 615, 915, 1215 and 
1615
X
Plasma-cfDNA 
X
X 
Peripheral blood (flow for 
TBNK)
X16
X16
X16
At the start of each cycle16
X16
Sparse PK (blood) 
X17
X17
X17
X17
X17
C3D117, C3D1517 and C5D117 only
X18
Genetics sample
X19
CT/PET Scan for disease 
assessments 
X20
At the start of Cycles 3, 5, 7, 9, 11, 13, and 
16
Premedication if needed
X
X
X
X24
X
Each dosing week
GSK2857916  
administration
X21
X21
X21
X21, 24
X
Each dosing week21
Steroid eye drops
X22
X22
X22
X22, 24
X22
Each dosing week22
Tumor biopsy for BCMA 
expression
X23
Adverse Events
Continuous
Concomitant Medications
X
Continuous
Survival Status
X25
Subsequent Treatment
X25
1.
Assessments scheduled on days of dosing should be done prior to drug administration, unless otherwise specified.  All other assessments can be done 3 days unless otherwise 
specified
2.
All Screening assessments must be performed within 14 days prior to first dose unless otherwise specified. Informed Consent must be signed before any study-specific 
assessments are performed.
3.
Screening examination to include BCVA (best-corrected visual acuity), slit lamp examination (with special focus on cornea), intraocular pressure, and dilated fundoscopic 
examination may be performed within 21 days prior to first dose.
4.
On-study exams, to include BCVA (best-corrected visual acuity) and slit lamp examination (with special focus on cornea); window for exams is up to 3 days prior to dosing. In the 
event that a subject has a dose delay due to a non-ocular toxicity and an ocular exam has been performed for that cycle, a repeat ocular exam 3 days prior to dosing may be 
omitted if the participant did not have corneal signs on the previous exam and does not have any new corneal symptoms. 


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5.
On initial (first infusion) dosing day, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +10 minutes and +30 minutes after SOI (5 min), EOI, and 1 hour 
post EOI.  On subsequent dosing days, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +30 minutes after SOI, and EOI.  On days where vital sign 
timepoints align with PK sampling timepoints, vital signs should be assessed prior to PK samples being drawn.  
6.
If completed within 72 hrs prior to the first dose, this assessment need not be repeated on Day 1 of Cycle 1.  Refer to Table 15 of the protocol for comprehensive list of lab tests.   
7.
Troponin will be measured at the local (troponin I or T) and central (troponin I) lab.  CK-MB at the local lab, or if not available by a central laboratory. 
8.
BNP to be measured locally, or if not available by a central laboratory, at screening; if cardiac workup is required due to safety concerns during the study, BNP should be 
measured.
9.
Perform only in women of child-bearing potential.  A serum pregnancy test should be performed at screening, and subsequent pregnancy tests may be either serum or urine
10. Final pregnancy test (serum or urine) must be performed in women of childbearing potential 60 days after last study treatment.
11. On dosing days, perform triplicate ECGs at predose (within 30 minutes prior to SOI) and EOI.  On days where ECG timepoints align with PK sampling timepoints, ECGs 
should be performed prior to PK samples being drawn (PK sample should be taken at the exact nominal time; refer to footnote 17).  At screening and End of Study, 
obtain a single ECG measurement.
12. At Screening, LVEF may be performed within 30 days prior to first dose. All ECHOs indicated on dosing days may be performed up to 7 days before dosing. ECHOs to be done 
locally and sent to GSK for central imaging storage.
13. A single sample for sBCMA will be collected at C1D8 predose, and at the End of Study visit.  sBCMA samples will also be collected on C1D1 at predose (within 30 minutes prior to 
SOI) and EOI (5 minutes).  On C1D15 and C2D1 collect at predose (within 30 minutes prior to SOI) and EOI (5 minutes)
14. Collect cytokines at predose (within 30 minutes prior to SOI) and EOI (5 min) (even when infusion is interrupted or halted) to assess allergic reaction.
15. All ADA samples will be collected prior to each infusion.
16. Sample(s) collected for analysis by central lab.
17. PK samples to be taken for both GSK2857916 and cys-mcMMAF measurement at C1D1 predose (within 30 minutes prior to SOI), EOI (just before EOI), 1 hour post EOI (5 min), 
and 3 hours post EOI (5 min); predose (within 30 minutes prior to SOI) and EOI (just before EOI) on C1D8, C1D15, C2D1, C2D15, C3D1, C3D15, and C5D1.
18. Collect 1 PK sample at each subject’s final visit.
19. Informed consent for optional genetics research should be obtained before collecting a sample.
20. CT/PET scans from within 21 days prior to first dose are acceptable.
21. Study drug administration 1 day window only.
22. Prophylaxis with prednisolone phosphate 1% or dexamethasone 0.1% 1 drops QID x 4 days starting 1 day prior to treatment.
23. Archived or fresh tissue required for BCMA testing.  Refer to Section 5.2.1 of the protocol Inclusion Criterion #4 for eligibility criteria. 
24. Also applies to C2D8.
25. Record subject’s survival status and whether subsequent treatment for disease was given.  Subject does not need to come in for visit.
Abbreviations:
ADA = Antibody Drug Antibody; ALP = alkaline phosphatase; BCVA = best corrected visual acuity; BNP = B-type natriuretic peptide; C1D1 = Cycle 1 Day 1, etc.; cfDNA = 
Circulating free DNA; CK = creatine kinase; CRP = C-reactive protein; EOI = End of Infusion; PD = Pharmacodynamics; PK = Pharmacokinetics; QID = 4 times a day; SOI = start 
of infusion


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16.3.
Appendix 3: Assessment Windows
No assessment windows will be applied.


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16.4.
Appendix 4: Study Phases and Treatment Emergent 
Adverse Events
16.4.1.
Study Phases
Study Phase
Definition
Pre-Treatment 
Date ≤ Study Treatment Start Date
On-Treatment
Study Treatment Start Date < Date 
Some datasets include the first dosing day as On-Treatment and some exclude the first 
dosing date as On-Treatment. 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. The first dosing day (Day 1) is considered to be On-Treatment for adverse 
events and concomitant medications.
16.4.1.1.
Study Time Periods for Concomitant Medications and Blood and Blood 
Supportive Care Products
Concomitant Medication and Blood and Blood Supportive Care Product start and end 
dates will be assigned to study time periods in relation to first dose of study treatment as 
defined below. The start date references time flag variables and end date reference time 
flag variables will be added to the concomitant medications and blood and blood 
supportive products datasets, respectively.

Start relative to treatment: Assign to 'BEFORE' if start date is prior to study 
treatment start date or if subject has not taken any study treatment or (start date is 
missing and end date is before study treatment start date). Else assign to 'DURING' if 
the start date falls into the on-therapy period as defined above or if subject is ongoing 
(not all study treatment discontinuation records completed) or start date is missing. 
Else assign to 'AFTER' if start date is after the on-therapy period.

End relative to treatment: Assign to 'BEFORE' if end date is prior to study treatment 
start date or if subject has not taken any study treatment. Else assign to 'DURING' if 
start date falls into the on-therapy period or if subject is ongoing (not all study 
treatment discontinuation records completed) or (end date is missing and start 
relative to treatment not 'AFTER'). Else assign to 'AFTER' if start date is after the 
on-therapy period or (end date is missing and start relative to treatment='AFTER').
Only on-therapy blood and blood supportive care products that start after the start of 
study treatment are included in the Blood Products and Blood Supportive Care Product 
summaries. Therefore, for summary tables, include blood and blood supportive care 
product records where start relative to treatment in ('DURING') and end relative to 
treatment in ('DURING','AFTER'). All data will be reported in listings. 
Concomitant medication start relative to treatment and end relative to treatment flags are 
used to select data to include in the Concomitant Medication summaries as follows:

Summary of Concomitant Medications: This summary will contain medications 
including those with start date prior to study treatment start date and continue 


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(missing end date or end date after study treatment start date) on therapy. Note that 
any medications with start date and end date prior to study treatment start date will be 
excluded. In addition, any medication that was started during post-therapy will be 
excluded. Include concomitant medication records where start relative to treatment in 
('BEFORE','DURING') and end relative to treatment in ('DURING','AFTER').

Summary of Concomitant Medications with On-Therapy Onset: This summary will 
contain medications with start date after study treatment start date. In addition, any 
medication that was started during post-therapy (see above for definition of post-
therapy) will be excluded. Include concomitant medication records where start 
relative to treatment in ('DURING') and end relative to treatment in 
('DURING','AFTER').
16.4.2.
Treatment Emergent Flag for Adverse Events
Flag
Definition
Treatment
Emergent

Study Treatment Start Date ≤ AE Start Date 

AE Start Date is missing
NOTES: 

If the study treatment stop date is missing, then the AE will be considered to be On-Treatment.

Time of study treatment dosing and start/stop time of AEs should be considered, if collected.


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16.5.
Appendix 5: Data Display Standards & Handling 
Conventions
16.5.1.
Reporting Process
Software

The currently supported versions of SAS software will be used.
Reporting Area
HARP Server
: US1SALX00259
HARP Compound
: arprod\gsk2859716\bma117159\
Analysis Datasets 

Analysis datasets will be created according to CDISC standards (SDTM IG Version 3.1.3 & ADaM IG 
Version 1.0.
Generation of RTF Files

RTF files will be generated for all tables.
16.5.2.
Reporting Standards
General

The current GSK Integrated Data Standards Library (IDSL) will be applied for reporting, unless 
otherwise stated (IDSL Standards Location: https://spope.gsk.com/sites/IDSLLibrary/SitePages/Home.aspx):

4.03 to 4.23: General Principles

5.01 to 5.08: Principles Related to Data Listings

6.01 to 6.11: Principles Related to Summary Tables

7.01 to 7.13: Principles Related to Graphics 

Do not include subject level listings in the main body of the GSK Clinical Study Report. All subject level 
listings should be located in the modular appendices as ICH or non-ICH listings
Formats

GSK IDSL Statistical Principles (5.03 & 6.06.3) for decimal places (DP’s) will be adopted for reporting of 
data based on the raw data collected, unless otherwise stated.

Numeric data will be reported at the precision collected on the eCRF.
The reported precision from non eCRF sources will follow the IDSL statistical principles but may be
adjusted to a clinically interpretable number of DP’s.
Planned and Actual Time

Reporting for tables, figures and formal statistical analyses:

Planned time relative to dosing will be used in figures, summaries, statistical analyses and 
calculation of any derived parameters, unless otherwise stated.

The impact of any major deviation from the planned assessment times and/or scheduled visit days 
on the analyses and interpretation of the results will be assessed as appropriate.

Reporting for Data Listings: 

Planned and actual time relative to study drug dosing will be shown in listings (Refer to IDSL 
Statistical Principle 5.05.1).

Unscheduled or unplanned readings will be presented within the subject’s listings. 


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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.
16.5.3.
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 
[Insert document name]. 
Note: Concentration values will be imputed as per GUI_51487
Descriptive Summary 
Statistics, Graphical 
Displays and Listings
Refer to IDSL PK Display Standards.
Refer to IDSL Statistical Principle 6.06.1.
Note: Concentration values will be imputed as per GUI_51487 for descriptive 
summary statistics/analysis and summarized graphical displays only. 
NONMEM/Pop PK 
File
Pop-PK file (CSV format) for the POP-PK analysis by Clinical Pharmacology 
Modelling and Simulation function will be created according to the data specification 
detailed in Section 16.9.1 Population Pharmacokinetic (PopPK) Dataset 
Specification.
NONMEM/PK/PD 
File
PK/PD file (CSV format) for the PK/PD analysis by Clinical Pharmacology Modelling 
and Simulation function will be created according to the data specification detailed 
in Section 16.10.1 Pharmacokinetic/Pharmacodynamic Dataset Specification.
Pharmacokinetic Parameter Derivation
PK Parameter to be 
Derived by 
Programmer
The following PK parameters will be derived by the Programmer: 
Pharmacokinetic Parameter Data
Is NQ impacted PK 
Parameters Rule 
Being Followed
Yes, refer to [Standards for Handling NQ Impacted PK Parameters].
Descriptive Summary 
Statistics, Graphical 
Displays and Listings
Refer to IDSL PK Display Standards. 


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16.5.4.
Extended Loss to Follow-up or Extended Time without an 
Adequate Assessment
For subjects, if two or more scheduled disease assessments are missed and are then 
followed by an assessment of PD or death, PFS will be censored at the last adequate 
assessment prior to PD or death. When the scheduled disease assessment is every 3 
weeks, a window of 49 days (6 weeks + 7 day window) will be used to determine 
whether there was an extended time without adequate assessment. That is, if the time 
difference between PD/death and last adequate assessment is more than 49 days, then 
PFS will be censored at the last adequate assessment prior to PD/death.
16.5.5.
Date Associated with Response
Investigator assessment of disease is entered in the eCRF on the VISIT form. The date of 
the VISIT is captured but the date of the response assessment is not captured separately. 
The date associated with response will be the visit date for the VISIT on which the 
investigator assessed disease. A disease assessment may occur at an unscheduled visit. 
The date of the unscheduled visit would be assigned to any response assessed on that 
date. In the following section, unless otherwise specified, the disease assessment denotes 
post-baseline assessment.


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16.6.
Appendix 6: Derived and Transformed Data
16.6.1.
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    
16.6.2.
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 = Treatment Stop Date – (Treatment Start 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 = Sum of Dose at Each Cycle

Dose intensity per cycle will be based on the formula:
Dose intensity Per Cycle = Cumulative Dose / Total Number of Cycles
16.6.3.
Efficacy
Laboratory Parameters
Serum M-protein, Urine M-protein, Serum FLC

If a laboratory value which is expected to have a numeric value for summary purposes, has a non-
detectable level reported in the database, where the numeric value is missing, but typically a character 
value starting with ‘<x’ or ‘>x’ (or indicated as less than x or greater than x in the comment field) is 
present, the number of significant digits in the observed values will be used to determine how much to 
add or subtract in order to impute the corresponding numeric value. 
o
Example 1: 2 Significant Digits =  ‘< x ‘ becomes x – 0.01
o
Example 2: 1 Significant Digit   =  ‘> x’ becomes x + 0.1
o
Example 3: 0 Significant Digits = ‘< x’ becomes x – 1    


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16.6.4.
Safety
Adverse Events
AE’S OF Interest

Corneal events

Thrombocytopenia

Neutropenia

Hematologic Toxicity

Infusion-related Reactions as collected in the eCRF


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16.7.
Appendix 7: Reporting Standards for Missing Data
16.7.1.
Premature Withdrawals
Element
Reporting Detail
General

Subject study completion (i.e. as specified in the protocol) was defined as:
o
For Part 1 (dose-escalation phase), a completed subject is one who has completed 
at least 1 cycle of study treatment and an End of Study Visit without events 
causing them to withdraw or discontinue from the study for reasons listed in 
Section 6.3 of the protocol.
o
For Part 2 (expansion cohort), a completed subject is one who has received at 
least one dose of study treatment without events causing them to withdraw or 
discontinue study treatment for reasons listed in Section 6.3 of the protocol and 
completed an End of Study Visit.
o
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 before the end of 
the study, has not been lost to follow-up, or has not withdrawn consent from study 
participation.

Withdrawn subjects may be replaced in the study.

All available data from participants who were withdrawn from the study will be listed 
and all available planned data will be included in summary tables and figures, unless 
otherwise specified.
16.7.2.
Handling of Missing Data
Element
Reporting Detail
General

Missing data occurs when any requested data is not provided, leading to blank fields on 
the collection instrument:
o
These data will be indicated by the use of a blank in subject listing displays. Unless 
all data for a specific visit are missing in which case the data is excluded from the 
table. 
o
Answers such as “Not applicable” and “Not evaluable” are not considered to be 
missing data and should be displayed as such.
Outliers

Any participants excluded from the summaries and/or statistical analyses will be 
documented along with the reason for exclusion in the clinical study report.
Responder 
Analysis 

For endpoints which determine the percentage of responders, subjects with 
unknown/not evaluable or missing best overall response will be assumed to be non-
responders, and will be included in the denominator when calculating the percentages.
Time to 
Event 

Because study treatment is dependent on the study endpoints (e.g., progression, i.e. 
not a fixed treatment duration), the length of treatment for each subject will depend on 
the efficacy and toxicity of the treatment, so the duration of treatment will vary across 
subjects. Similarly the duration of follow up will also vary. All available time-to-event 
data will be analyzed using suitable statistical methods; subjects with shorter treatment 
and follow-up due to the natural history of their disease or medical necessities of the 
treatment of their disease will not be considered to have missing time-to-event data.


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16.7.2.1.
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. The imputed AE 
dates will only to be used in the figures “Profile Plot for Patients with No Corneal Event 
or Grade 1 Corneal Event” and “Profile Plot for Patients with Grade 2 or Higher Corneal 
Events”.

Imputed dates will not be displayed in listings. However, where necessary, display 
macros may impute dates as temporary variables for the purpose of sorting data in 
listings only. In addition, partial dates may be imputed for ‘slotting’ data to study time 
periods or for specific analysis purposes as outlined below.
Adverse 
Events

The eCRF allows for the possibility of partial dates (i.e., only month and year) to be 
recorded for AE start and end dates; that is, the day of the month may be missing.
o
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. 
Missing Start Day: First of the month will be used unless this is before the start 
date of study treatment; in this case the study treatment start date will be used and 
hence the event is considered On-treatment as per Appendix 4: Study Phases and 
Treatment Emergent Adverse Events.
o
Missing Stop Day: Last day of the month will be used, 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.
Concomitant 
Medications

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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Element
Reporting Detail
Anti-Cancer 
Therapy 
(Where 
applicable),  
Radiotherap
y and  
Surgical 
Procedures 
for Time-to-
Event 
Endpoint 
and 
Response

Start dates for follow-up anti-cancer therapy, radiotherapy (where applicable), and 
surgical procedures (where applicable) will be temporarily imputed in order to define 
event and censoring rules for progression-free survival, response rate, time to 
progression, duration of response or time to response (i.e. start date for new anti-
cancer therapy). The imputed dates will not be stored on the anti-cancer therapy, 
radiotherapy, or surgical procedure datasets.

If missing start day, month, and year, then no imputation for completely missing dates

If missing start day and month, then no imputation should be done

If missing start day, then do the following:

If partial date falls in the same month as the last dose of study treatment, then assign to 
earlier of (date of last dose of study treatment+1, last day of month). 

If partial date falls in the same month as the subject’s last assessment and the subject’s 
last assessment is PD, then assign to earlier of (date of PD+1, last day of month). 

If both rules above apply, then assign to latest of the 2 dates 

Otherwise, impute missing day to the first of the month.

If missing end date, then no imputation should be done.


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16.8.
Appendix 8: Values of Potential Clinical Importance
16.8.1.
Laboratory Parameters
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 v4.0) will be used to 
assign grades to the relevant laboratory parameters. NCI-CTCAE v4.0 can be found at
http://ctep.cancer.gov/reporting/ctc.html. 
For laboratory data which are not listed in the NCI CTCAE v4.0, a summary of values 
outside the normal range will be provided.
16.8.2.
ECG Parameters and vital signs
For ECG and vital signs, the most updated IDSL standard up to the RAP effective date 
will be followed


CONFIDENTIAL
BMA117159
97
16.9.
Appendix 9: Population Pharmacokinetic (PopPK) Analyses
16.9.1.
Population Pharmacokinetic (PopPK) Dataset Specification
Any deviations between the dataset specification and the final dataset will be documented 
in the population pharmacokinetic analysis report.
General Description:
1.
The type of variables should be either NUM or DATE/TIME unless specified otherwise
2.
The dataset is sorted by ID, RTFDD, ANALN, ASCENDING EVID unless specified 
otherwise
3.
The data items (columns) in the analysis-ready data file will be in the same order as 
follows.
4. 
Exclude observations with DTYPE=IMPUTE
5. 
Include PKFL=Y (applicable to all datasets)
6.
Same rules are applied for other baseline covariates. Baseline rules are as follows:
• Use baseline value as defined by Stats in the lab test datasets;  
• If not defined by Stats, set to measurement nearest to, but prior to, time of first dose
• Only in cases where Day 1 measurement is not available, but screening measurement is, 
the screening values will be used.
7.
3 significant figures for all values.
Column 
Header
Data Item
Codes
Derivation/Comments
Source data 
set 
C
Line 
number/exclusion 
identifier
Row Number
STM
DRM
PFD
Set to line/row number unless one or more of the 
following conditions are met, then set to code: 
•
STM = If a PK sample was taken but the date 
and/or time of the sample is missing and cannot 
be derived
•
DRM= PK samples for which dosing records are 
missing
•
PFD=PK samples with CONC reported as 
NA/NR/NQ/BQL/missing at pre-dose in CYCLE 
=1
derived
STUDY
Study ID
1 = BMA117159
adpc
SUBJID
Subject identifier 
from source data 
SUBJID = SUBJID
adsl
ID
NONMEM subject 
identifier
Sequential subject identifier across studies after 
data is sorted by SUBJID. Starting with
derived
P


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Column 
Header
Data Item
Codes
Derivation/Comments
Source data 
set 
AMT
Amount of 
GSK2857916 given 
(in mg)
AMT = ALTDOSE, where PARAMCD=ALTDOSE 
only on the dosing line. For all other lines use “.” 
adex
INFD
Infusion Duration 
(day)
(AENDTM-ASTDTM)/60/60/24
This value will only be used on the dosing line. For 
all other lines use “.”
adex
INFH
Infusion Duration (h)
(AENDTM-ASTDTM)/60/60
This value will only be used on the dosing line. For 
all other lines use “.”
adex
RATED
Rate of infusion 
(mg/day)
RATED = AMT/INFD; where INFD is the infusion 
duration and is computed from start and stop time of 
infusion (in days)
This value will only be used on the dosing line. For 
all other lines use “.”
derived
RATEH
Rate of infusion 
(mg/h)
RATEH = AMT/INFH; where INFH is the infusion 
duration and is computed from start and stop time of 
infusion (in h)
This value will only be used on the dosing line. For 
all other lines use “.”
derived
RTFDD
Relative time from 
start of first infusion 
on study (day)
RTFDH=((ADTM-ASTDTM)/60/60/24)
adpc, adex
RTFDH
Relative time from 
start of first infusion 
on study (h)
RTFDD=((ADTM-ASTDTM)/60/60));
adpc, adex
RTLDD
Relative time from 
start of the most 
recent dose on study 
(day)
RTLDD= RTLDD/24
derived
RTLDH
Relative time from 
start of the most 
recent dose on study 
(h)
AWNLRT= RTLDH
adpc
NOMTLD
D
Planned nominal 
time relative to start 
of most recent 
infusion (day)
NOMTLDH/24
adpc
NOMTLD
H
Planned nominal 
time relative to start 
of most recent 
infusion (h)
Derive from PCTPT
when (PCTPT ='PRE-DOSE), NOMTLDH=0;
when (PCTPT='DOSE'), NOMTLDH =0;
when (PCTPT =”30M POST START OF INFUSION 
(SOI)"), NOMTLDH =0.5;
when (PCTPT ="END OF INFUSION (EOI)"), 
NOMTLDH =1;
when (PCTPT ="1 HOUR POST-EOI"), NOMTLDH 
=2;
when (PCTPT ="3 HOURS POST-EOI"), NOMTLDH 
=4;
when (PCTPT ="8 HOURS POST-EOI"), NOMTLDH 
=9;
when (PCTPT ="24 HOURS POST-EOI"), 
NOMTLDH =25;
when (PCTPT ="7 DAYS POST-EOI"), NOMTLDH 
=168;
when (PCTPT ="14 DAYS POST-EOI"), NOMTLDH 
adpc


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99
Column 
Header
Data Item
Codes
Derivation/Comments
Source data 
set 
=336;
when (PCTPT ="END OF STUDY"), NOMTLDH 
=10000;
otherwise  NOMTLDH =.;
CTIME
Clock time sample 
was obtained
Clock time 
(24 h) ‘00:00’
TIMEPART (EVENT)
Format TIME5.
all dataset
DATE
Date of event 
(MM/DD/YYYY)
DATEPART (EVENT)
Format DATE9.
all dataset
ANALN
Analyte
1= 
ADC(antibod
y-drug 
conjugate)
2= 
TOTALMAB(t
otal antibody 
including 
complex)
3= 
MMAF(cys-
mcMMAF)
This value will be used on all lines except for dosing 
record line where missing “.” will be used.
EXCLUDE MAB
PARAMCD in (P1RES, P5RES, P7RES), assign 
ANALN =3, 1, 2 respectively
adpc
DV
Plasma 
concentration 
(ng/mL) of 
GSK2857916 
(antibody-drug 
conjugate), total 
antibody (including
complex) and cys-
mcMMAF
If AVALC=NA/NR/NQ/BQL/missing, set DV= “.” 
Else DV=AVAL
When PARAMCD=P1RES, then DV=AVAL/1000
[Convert cys-mcMMAF from pg/mL to ng/mL 
precision (3 significant figures).For example, 0.111 
pg/mL= 0.000111 ng/mL]
adpc
DNDV
Dose-normalized 
plasma 
concentration[(ng/m
L)/(mg/kg)] of 
GSK2857916 
(antibody-drug 
conjugate), total 
antibody (including
complex) and cys-
mcMMAF
DNDV = DV (ng/mL)/AVAL;
where AVAL=adex.PARAMCD=ADOSE (mg/kg)
For DV = “.”, set DNDV = “.”
adpc, adex
DVNM
Plasma 
concentration (nM) 
of GSK2857916 
(antibody-drug 
conjugate), total 
antibody (including
complex) and cys-
mcMMAF
For ANALN = 1, DVNM = DV(ng/mL)/152.1
For ANALN = 2, DVNM = DV(ng/mL)/152.1
For ANALN = 3, DVNM = DV(ng/mL)/1.045
For DV = “.”, set DVNM = “.”
adpc
DNDVN
M
Dose-normalized 
plasma 
concentration[(nM)/(
mg/kg)] of 
GSK2857916 
(antibody-drug 
conjugate), total 
antibody (including
DNDVNM = DVNM (nM)/ AVAL;
where AVAL=adex.PARAMCD=ADOSE (mg/kg)
For DVNM = “.”, set DNDVNM = “.”
adpc


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100
Column 
Header
Data Item
Codes
Derivation/Comments
Source data 
set 
complex) and cys-
mcMMAF
LNDV
Natural logarithm of 
the plasma 
concentration of 
GSK2857916 
(ng/mL) (antibody-
drug conjugate), 
total antibody 
(including
complex) and cys-
mcMMAF
• If DV = “.” then LNDV = “.”
• Else LNDV = loge(DV)
adpc
LNDNDV Natural logarithm of 
dose-normalized 
plasma 
concentration[(ng/m
L)/(mg/kg)] of 
GSK2857916 
(antibody-drug 
conjugate), total 
antibody (including
complex) and cys-
mcMMAF
If DNDV = “.” then LNDNDV = “.”
Else LNDNDV = loge(DNDV)
adpc
LNDVNM Natural logarithm of 
plasma 
concentration (nM) 
of GSK2857916 
(antibody-drug 
conjugate), total 
antibody (including
complex) and cys-
mcMMAF
If DVNM = “.” then LNDVNM = “.”
Else LNDVNM = loge(DVNM)
adpc
LNDNDV
NM
Natural logarithm of 
dose-normalized 
plasma 
concentration[(nM)/(
mg/kg)] of 
GSK2857916 
(antibody-drug 
conjugate), total 
antibody (including
complex) and cys-
mcMMAF
If DNDVNM = “.” then LNDNDVNM = “.”
Else LNDNDVNM = loge(DNDVNM)
adpc
DV2
Plasma 
concentration 
(ng/mL) of 
GSK2857916 
(antibody-drug 
conjugate), total 
antibody (including
complex) and cys-
mcMMAF
If adpc.AVALC=NA/NR/missing, set DV2= “.” 
If AVALC=NQ/BQL, set DV2 = “LLOQ/2”
When PARAMCD=P1RES, then DV2=AVAL/1000;
[Convert cys-mcMMAF from pg/mL to ng/mL 
precision (3 significant figures). For example, 0.111 
pg/mL= 0.000111 ng/mL]
adpc
DNDV2
Dose-normalized 
plasma 
concentration[(ng/m
DNDV2 = DV2(ng/mL)/ AVAL;
where AVAL=adex.PARAMCD=ADOSE (mg/kg)
adpc, adex


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101
Column 
Header
Data Item
Codes
Derivation/Comments
Source data 
set 
L)/(mg/kg)] of 
GSK2857916 
(antibody-drug 
conjugate), total 
antibody (including
complex) and cys-
mcMMAF
For DV2 = “.”, set DNDV2 = “.”
DVNM2
Plasma 
concentration (nM) 
of GSK2857916 
(antibody-drug 
conjugate), total 
antibody (including
complex) and cys-
mcMMAF
For ANALN = 1, DVNM2 = DV2(ng/mL)/152.1
For ANALN = 2, DVNM2 = DV2(ng/mL)/152.1
For ANALN = 3, DVNM2 = DV2(ng/mL)/1.045
For DV2 = “.”, set DVNM2 = “.”
adpc
DNDVN
M2
Dose-normalized 
plasma 
concentration[(nM)/(
mg/kg)] of 
GSK2857916 
(antibody-drug 
conjugate), total 
antibody (including
complex) and cys-
mcMMAF
DNDVNM2 = DVNM2 (nM)/ADOSE (mg/kg)
For DVNM2 = “.”, set DNDVNM2 = “.”
adpc
LNDV2
Natural logarithm of 
the plasma 
concentration of 
GSK2857916 
(ng/mL) (antibody-
drug conjugate), 
total antibody 
(including
complex) and cys-
mcMMAF
• If DV2 = “.” then LNDV2 = “.”
• Else LNDV2 = loge(DV2)
adpc
LNDNDV
2
Natural logarithm of 
dose-normalized 
plasma 
concentration[(ng/m
L)/(mg/kg)] of 
GSK2857916 
(antibody-drug 
conjugate), total 
antibody (including
complex) and cys-
mcMMAF
If DNDV2 = “.” then LNDNDV2 = “.”
Else LNDNDV2 = loge(DNDV2)
adpc


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Column 
Header
Data Item
Codes
Derivation/Comments
Source data 
set 
LNDVNM
2
Natural logarithm of 
plasma 
concentration (nM) 
of GSK2857916 
(antibody-drug 
conjugate), total 
antibody (including
complex) and cys-
mcMMAF
If DVNM2 = “.” then LNDVNM2 = “.”
Else LNDVNM2 = loge(DVNM2)
adpc
LNDNDV
NM2
Natural logarithm of 
dose-normalized 
plasma 
concentration[(nM)/(
mg/kg)] of 
GSK2857916 
(antibody-drug 
conjugate), total 
antibody (including
complex) and cys-
mcMMAF
If DNDVNM2 = “.” then LNDNDVNM2 = “.”
Else LNDNDVNM2 = loge(DNDVNM2)
adpc
BQL
Flag for BQL 
concentration
0 or 1
Set to 1 if adpc.AVALC= NQ/BQL; 
Else set to 0
adpc
MDV
Missing dependent 
variable flag.
0 or 1
1 for DV = “.” and dosing line. 
0 otherwise
adpc
MDV2
Missing dependent 
variable flag 2
0 or 1
1 for DV2= “.”and dosing line. 
0 otherwise
adpc
EVID
Flag indicating
whether it is dosing 
admin info or drug 
concentration data.
0 or 1
1 on dosing line
Set to 0 for all other lines
adex, adpc
OCC
Cycle number
>0
1 = Cycle 1, 2 = Cycle 2, 3 = Cycle 3 ,4 = Cycle 4,5 
= Cycle 5,… etc
EOT=999
Derive from AVISIT
adpc
IDOSE
GSK2857916 initial 
cycle dose (mg/kg)
>0
IDOSE=adex.TRT01A; strip off units
adex
ADOSE
GSK2857916 actual 
cycle dose (mg/kg)
>0
ADOSE= AVAL;
where AVAL=adex.PARAMCD=ADOSE
adex
CMT
Compartment
>0
1 = Central Compartment for antibody-drug 
conjugate (Plasma concentration of antibody-drug 
conjugate ANALN=1)
3 = Central Compartment for total antibody 
(including complex) (Plasma concentration (DV) of 
total antibody for ANALN=2)
5 = Central Compartment for cys-mcMMAF (Plasma 
concentration(DV) of cys-mcMMAF for ANALN=3)
On Dosing line CMT= 1


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Column 
Header
Data Item
Codes
Derivation/Comments
Source data 
set 
AGE
Age (years)
•
Use value as defined by Stats; 
•
If not defined by Stats, AGE = date of first 
dose – date of birth
•
If date of birth is missing, AGE = -99
adsl
GENDE
R
Gender
0 or 1
Male = 1
Female = 0
•
If sex is missing, GENDER = -99
adsl
BWT
Baseline Weight (kg)
Baseline rules:
•
Use baseline value as defined by Stats in 
the lab test datasets;  
•
If not defined by Stats, set to weight 
measurement nearest to, but prior to, time of first 
dose
•
Only in cases where Day 1 weight is not 
available, but screening weight is, the screening 
values will be used.
Fill in BWT in all rows for each subject
Same rules are applied for other baseline 
covariates
adsl
HT
Height (cm)
Height at baseline in cm
Fill in HT in all rows for each subject
adsl
LNWT
Ln transformed 
weight (kg)
LNWT = loge(BWT)
Fill in LNWT in all rows for each subject
adsl
LWT
Lean Weight (kg)
Male: 0.32810• BWT(kg) + 0.33929• HT(cm) -
29.5336 
Female: 0.29569• BWT (kg) + 0.41813• HT (cm) -
43.2933
Ref: Hume, 1966
Fill in LWT in all rows for each subject
adsl
LNLWT
Ln transformed lean 
Weight (kg)
LNLWT= loge(LWT)
Fill in LNLWT in all rows for each subject
adsl
BBSA
Baseline Body 
Surface Area (m2)
Baseline BSA (m2)
BBSA = 0.024265 • HT(cm)0.3964 • BWT(kg)0.5378
Fill in BBSA in all rows for each subject
adsl
BBMI
Baseline Body Mass 
Index (kg/m2)
BBMI = BWT(kg)/(HT(cm)/100)2
Assign BBMI = -99 if negative values would be 
derived for any of BBMI
Fill in BBMI in all rows for each subject
adsl
BFFM
Baseline fat-free 
mass (kg)

If Male, BFFM = 
(9270*BWT(kg))/(6680+(216*BBMI(kg/m2)))

If Female, BFFM = 
(9270*BWT(kg))/(8780+(244*BBMI(kg/m2)))
Assign FFM = -99 if negative values are derived for 
any of BMI, BSA, FFM or IBW. 
Fill in BFFM in all rows for each subject
adsl
CANCER Cancer type
0 or 1
0=Multiple Myeloma, 1=BCMA positive Lymphomas
If TRT01AN = 12, then CANCER=1, else 
CANCER=0 Fill in CANCER in all rows for each 
subject
all datasets
BSBCMA sBCMA level at 
baseline (ng/mL)
Baseline value is pre-dose on Cycle 1 Day 1. For 
PARAMCD = SBCMAG, get the values from AVAL 
column.
When AVAL is missing:
•
and AVALC = ALQ:  set to LBULOQ
•
and AVALC = BLQ:  set to LBLLOQ/2 
adbiomrk
PARAMCD = 
SBCMAG 
when 
ABLFL=Y.


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Column 
Header
Data Item
Codes
Derivation/Comments
Source data 
set 
•
and AVALC = missing:  set to -99
Fill in the BSBCMA in all rows for each subject
SBCMA
sBCMA level 
(ng/mL)
For PARAMCD = SBCMAG, get the values from 
AVAL column.
SBCMA is propagated forward from the most recent 
measurement for all observations up to the next 
sBCMA measurement (LOCF).
When AVAL is missing:
•
and AVALC = ALQ:  set to LBULOQ
•
and AVALC = BLQ:  set to LBLLOQ/2 
•
and AVALC = missing:  propagate prior 
SBCMA value forward until the next 
measured SBCMA
Please capture the values corresponding to the PK 
time points.
adbiomrk
PARAMCD = 
SBCMA
SBCMA
GC
Complex BCMA 
(ng/mL)
For PARAMCD = SBCMAGC, get the values from 
AVAL column.
SBCMAGC is propagated forward from the most 
recent measurement for all observations up to the 
SBCMAGC measurement (LOCF).
When AVAL is missing:
•
and AVALC = ALQ:  set to LBULOQ
•
and AVALC = BLQ:  set to LBLLOQ/2 
•
and AVALC = missing:  propagate prior 
SBCMAGC value forward until the next measured 
SBCMAGC
Please capture the values corresponding to the PK 
time points.
adbiomrk
PARAMCD = 
SBCMAGC
BCRCL
Baseline Creatinine 
Clearance 
(mL/min/1.73 m2)
eGFR = 175 × (Scr)-1.154 × (Age)-0.203 × (0.742 if 
female) × (1.212 if African American)
Scr = AVAL; AVAL=adlab.PARAMCD =LB1404 and 
ABLFL=Y
Convert units (µmol/L) to (mg/dL) using the 
following formula:
To convert µmol/L to mg/dL, multiply by 0.0113.
Age is expressed in years.
Fill in the BCRCL in all rows for each subject
Assign-99 if missing
adlab;
PARAMCD=L
B1404
CRCL
Creatinine 
Clearance 
(mL/min/1.73 m2)
eGFR = 175 × (Scr)-1.154 × (Age)-0.203 × (0.742 if 
female) × (1.212 if African American)
Scr = AVAL; AVAL=adlab.PARAMCD = 
PARAMCD=LB1404. Convert units (µmol/L) to 
(mg/dL) using the following formula:
To convert µmol/L to mg/dL, multiply by 0.0113.
Age is expressed in years.If AGE is changing during 
the course of treatment, then use baseline AGE. 
CRCL is propagated forward from the most recent 
measurement for all observations up to the next 
CRCL measurement (LOCF). Please capture the 
values corresponding to the PK time points.
adlab
BALT
Baseline ALT (IU/L)
BALT = AVAL; AVAL=adlab.PARAMCD =LB1227 
and ABLFL=Y
Fill in BALT in all rows for each subject
adlab


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Column 
Header
Data Item
Codes
Derivation/Comments
Source data 
set 
BAST
Baseline AST (IU/L)
BAST = AVAL; AVAL=adlab.PARAMCD =LB1273 
and ABLFL=Y
Fill in BAST in all rows for each subject
adlab
BALB
Baseline Albumin 
(g/L)
BALB = AVAL; AVAL=adlab.PARAMCD =LB1216 
and ABLFL=Y
Fill in BALB in all rows for each subject
adlab
BBILI
Baseline Total 
Bilirubin (mg/dL)
BALB = AVAL; AVAL=adlab.PARAMCD =LB1282 
and ABLFL=Y
Fill in BBILI in all rows for each subject
adlab
BIGG
Baseline serum IgG 
(g/L)
BIGG = AVAL; AVAL=adlab.PARAMCD =LB1566 
and ABLFL=Y
If a prior-to-first-dose-of- GSK2857916 lab test value 
was not available, set as -99
Fill in BIGG in all rows for each subject
adlab
IGG
Serum IgG (g/L)
BIGG = AVAL; AVAL=adlab.PARAMCD =LB1566
Missing values use -99.
IGG is propagated forward from the most recent 
measurement for all observations up to the next IGG 
measurement (LOCF). Please capture the values 
corresponding to the PK time points.
adlab
MAXPRE
D
Maximum reduction 
in M-protein or FLC
Obtain AVAL for PARAMCD=MAXPRED.
When AVAL is missing, MAXPRED = -999 
adrs
RESPRA
TIO
Transform MAXRED 
to a ratio to baseline
RESPRATIO = max((100+MAXPRED)/100,0.001)

When MAXRED is missing, MAXPRED = -
999 and RESPRATIO= -99

When MAXPRED is less than -100 e.g. -
100.15, RESPRATIO = negative (It is 
negative but greater than -8.99), then 
update RESPRATIO = 0.001 

When MAXPRED is equal to -100, 
RESPRATIO = 0, then update 
RESPRATIO = 0.001
adrs
RACE
Subject race
1=White, or 
White/Cauca
sian, or 
White/Cauca
sian -
European 
Heritage
2=Asian 
3= Black or 
African 
American, or 
Black/African 
American, or 
Black -
African 
American or 
African 
Heritage
4= American 
If race is missing, set to other (use CRF/Stats 
coding for other)
Fill in RACE in all rows for each subject
adsl


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106
Column 
Header
Data Item
Codes
Derivation/Comments
Source data 
set 
Indian or 
Alaska 
Native, or 
Alaska 
Native or 
American 
Indian, or 
Alaksa 
Native or 
American 
Indian from 
North/Central
/South 
America
5= Native 
Hawaiian or 
Other Pacific 
Islander
6= Multi-
racial: White 
Caucasian + 
Alaksa 
Native or 
American 
Indian
ETHN
Subject ethnicity
1 = Hispanic 
or Latino
2 = Non-
Hispanic
-99  = 
Missing

Same coding as CRF/Stats

Fill in ETHN in all rows for each subject
adsl
CNC 
Country code 
1 = Canada, 
2 = UK 
3 = US
Fill in CNC in all rows for each subject
adsl


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Column 
Header
Data Item
Codes
Derivation/Comments
Source data 
set 
IMMU
Immunogenicity 
Outcome by 
Collection Time
0 = negative
1 = positive
PARAMCD
IM
MU
PARAMCD = 
AGBABDS
PARAMCD = 
AGBABDC
AVA
LC
NEGATIVE
MISSING
0
AVA
LC
POSITIVE
POSITIVE
1
AVA
LC
POSITIVE
NEGATIVE
0
AVA
LC
POSITIVE
MISSING
-99
AVA
LC
MISSING
ANY
-99
IMMU may not have been assayed at all PK visits. 
For visits between IMMU visits, imputation rules are 
as follows:
(1) When there is no change in IMMU between 
IMMU visits, all PK visits in between will be 
imputed with the same IMMU
(2) When IMMU changes from 0 to 1, impute 
IMMU=1 from the first record after the record 
known to be IMMU=0
When IMMU changes from 1 to 0, impute IMMU = 1 
until the record known to be IMMU=0
adis
IMM
Overall 
Immunogenicity 
Outcome
0=anti-
GSK3174998 
negative, 1=anti-
GSK3174998 
positive (at least one 
postdose) 
0 = negative
1 = positive
-99 = 
missing

If IMMU = 1 at any observation for a subject, 
IMM = 1

else if all IMMU = -99, IMM = -99
Else IMM = 0
Fill in IMM in all rows for each subject
16.9.2.
Population Pharmacokinetic (PopPK) Methodology
The primary goal of this analysis is to characterize the population pharmacokinetics of 
GSK2857916 and associated analytes after intravenous administration of GSK2857916 in 
subjects with multiple myeloma. This analysis will be performed by CPMS and reported 
separately. 


CONFIDENTIAL
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108
A summary of the planned population pharmacokinetic analyses is outlined below:

Exploratory data analyses will be performed to understand the content of the analysis 
dataset with respect to the anticipated models, to search for extreme values and/or 
potential outliers, to examine the correlation between covariates, and to assess 
possible trends in the data. 

Drug concentration-time data will be subjected to nonlinear mixed effects modelling 
using appropriate validated software to develop a population PK model.

Based on the preliminary analysis, log-transformed drug concentration data for 
GSK2857916 ADC will be subjected to analysis using a two-compartment IV 
infusion model parameterized using either clearances and distribution volumes, 
micro-constants or macro-constants (A, B, ALPHA and BETA), depending on 
parameters to be estimated. A similar approach may be used on the data from the 
three analytes (ADC, total antibody, and cys-mcMMAF) together.

Inter-individual or between-subject variability (IIV or BSV) will be initially modeled 
using an exponential random effects model. Random effects for clearances and 
volumes or A and B and BETA will be incorporated, depending on model 
parameterization used. If the goodness-of-fit plots reveal potential biases in the 
random effects model, alternative random effects models may be considered.

An additive error model on a log-transformed data scale reflecting an exponential 
error residual variability model will initially be used to describe the residual 
variability. If the goodness-of-fit plots reveal potential biases in the residual 
variability model, other residual error models will be considered as appropriate. 

Covariate analysis will be performed to explore measurable sources of PK 
variability. Different approaches may be evaluated for covariate model building 
including a step-wise process consisting of a forward and a backward selection 
procedure and/or a full-model approach. Some of the prospectively identified 
covariates are listed below: 

Continuous covariates such as age, albumin, measures of body size (e.g., body 
weight, body surface area, body mass index, lean body mass); 

Categorical covariates such as gender, race, disease status, immunogenicity 
status, and geographic region.

Non-parametric bootstrapping may be performed to test model robustness. The 
model performance may be evaluated by performing predictive check. 

Individual post hoc estimated PK parameters will be summarized descriptively.  

Individual subject PK parameters and exposure measures for Cycle 1 will be 
estimated and documented for the purposes of any subsequent exposure-response 
(PK/PD) analyses.
Any analyses not described a priori but undertaken based on emerging data will be 
described in detail in the report.


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Data handling considerations are summarized below:

Drug concentration data which are below the lower limit of quantification, LLQ, 
(NQ or BLQ) are not reported as a numeric value. Such NQ observations will be 
either discarded or handled in a special way. When the frequency of NQ is small, the 
NQ values will be excluded, since discarding NQ values in this case introduces little 
bias [Beal, 2001]. In situations where there are a large percentage of NQ values, 
other strategies which may reduce estimation bias will be considered [Beal, 2001; 
Hing, 2001; Ahn, 2008]. The total number and percentage of NQ values will be 
calculated and the rationale for the method for handling these NQ values will be 
documented in the final report. In situations with large number of NQ values, the 
predictive performance of the model will be assessed to compare the agreement 
between observed versus predicted proportion of samples below the LLQ.

Concentrations that are inconsistent pharmacokinetically with the drug 
concentration-time profile within an individual may be considered as outliers and 
subsequently excluded from the dataset or analysis. Visual inspection of individual 
and pooled data and weighted residuals during analysis may be used to identify such 
outliers. Any such exclusion will be reported and discussed in the analyses summary.

Missing data will be handled in the following way:

Subjects who withdrew from the study and did not provide any PK samples and do 
not have adequate sampling and/or covariate information will be excluded from the 
analysis.

If dosing and/or sampling times are missing, the relevant concentrations may be 
excluded from the analysis dataset and summarized in an exclusion listing file. 
Alternatively, the nominal times of the respective doses and/or samples may be 
utilized. 

Imputations of any covariate value will only be performed if the variable is missing 
for less than 10% of the subjects. For continuous covariates, missing values for an 
individual subject will be imputed as the gender-specific median value for the study. 
Any changes to the imputation methods will be justified and documented. If the 
percentage of missing data is greater than 10%, the variable will only be evaluated in 
exploratory graphical displays and not in the population analyses. Subjects from race 
categories with an insufficient number for analysis (typically less than 10% of the 
subject population) may be re-grouped and/or defined as race “Other.”


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16.10.
Appendix 10: Pharmacokinetic / Pharmacodynamic 
Analyses
16.10.1.
Pharmacokinetic / Pharmacodynamic Dataset Specification
Dataset specifications for exposure-response analyses of efficacy and of corneal toxicity 
are provided. Any deviations between the dataset specifications and the final datasets 
will be documented in the population pharmacokinetic analysis report.
For corneal toxicity 
Column Header
Data Item
Codes
Derivation/Comments
Source 
data set
C
Line 
number/exclusion
identifier
Row 
Number
Set to line/row number 
adae
STUDY
Study ID
1 = BMA117159
adsl
SUBJID
Subject identifier 
from source data 
SUBJID = SUBJID
adsl
ID
NONMEM subject 
identifier
Sequential subject identifier across 
studies after data is sorted by SUBJID. 
Starting with
TOXTYPE
This variable is 
created to separate 
out Grade 1 toxicity 
from Grade 2 and 
higher.
1,2
2 separate datasets with one line per 
subject:
TOXTYPE = 1 for 1st occurrence of 
corneal event (CQ01NAM = Corneal 
Event). If CQ01NAM = missing, add 1 line 
for that subject.
TOXTYPE = 2 for 1st occurrence of 
corneal event (CQ01NAM = Corneal 
Event) with AETOXGRN ≥ 2. If 
CQ01NAM = missing, add 1 line for that 
subject.
After these 2 datasets are complete, 
merge them.
adae
CORTOX
Presence or Absence 
of Corneal toxicity
0 or 1
When CQ01NAM ="Corneal Event", then 
CORTOX=1.
When CQ01NAM =missing, then 
CORTOX=0.
adae
AETOXGRN
Standard Toxicity 
Grade
0,1,2,3
adae
TTECORTOX
Time to corneal 
toxicity event (day)

For TOXTYPE = 1 and 
CORTOX = 1, then 
TTECORTOX = AESTDY 

When TOXTYPE = 1 and 
CORTOX = 0, then 
TTECORTOX =  (TRTSDT, 
LSTCTDT is coming from adsl 
dataset)

For TOXTYPE = 2 and 
CORTOX = 1, then 
adae,
adsl
PP


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Column Header
Data Item
Codes
Derivation/Comments
Source 
data set
TTECORTOX = AESTDY 

When TOXTYPE = 2 and 
CORTOX=0, then TTECORTOX 
= LSTCTDT – TRTSDT+ 1
DOAE
Duration of adverse 
event (days)

When CQ01NAM = Corneal 
Event and AONGO=N and 
AENDT= blank, then DOAE = 
ADURN; 

When CQ01NAM = Corneal 
Event and AONGO = N and 
AENDT= D, then DOAE = -99; 

When CQ01NAM = Corneal 
Event and AONGO=Y, then 
DOAE = LSTCTDT – AESTDY 
+ 1; 

When CQ01NAM = missing, 
then DOAE = 0; 
adae, 
adsl
DOAECFLCD
DOAE Censoring 
Flag Code
0 or 1
When AONGO=N, then DOAECFLCD=0
When AONGO=Y, then DOAECFLCD=1
adae
LNDOAE
Log of duration of 
adverse event
LNDOAE = Log(DOAE);
When DOAE=-99, LNDOAE =-99;
When DOAE=0, LNDOAE=0
adae
CUMAMTCT
Cumulative dose to 
TTECORTOX (mg)
For corneal toxicity that occurred on 
dosing days, the dose on the corneal 
toxicity day was not included in the 
cumulative dose calculation. 
adex. 
adae
Q4CUMAMTCT
Quartile of 
CUMAMTCT
0,1,2,3
derived
Q5CUMAMTCT
Quintile of 
CUMAMTCT
0,1,2,3,4
derived
CUMAUCCT
Cumulative AUC to 
TTECORTOX 
(ug.day/mL)
(Cumulative dose to 
TTECORTOX)/Individual Clearance of 
ADC
popPK 
output, 
adae
Q4CUMAUCCT
Quartile of 
CUMAUCCT
0,1,2,3
derived
Q5CUMAUCCT
Quintile of 
CUMAUCCT
0,1,2,3,4
derived
TAAUCCT
Time-average AUC 
till TTECORTOX 
(AUC/day)
The area under the plasma ADC 
concentration–time curve (AUC) per day 
(AUC/day) will be derived for each patient 
using the available ADC dosing 
information, individual patient oral 
clearance (CL/F) values from the 
population pharmacokinetic model, and 
the time to the occurrence of the corneal 
toxicity.
popPK 
output, 
adae
Q4TAAUCCT
Quartile of TAAUCCT 0,1,2,3
derived
Q5TAAUCCT
Quintile of TAAUCCT 0,1,2,3,4
derived
CANCER
Cancer type
0 or 1
0=Multiple Myeloma, 1=BCMA positive 
Lymphomas
If TRT01AN = 12, then CANCER=1, else 
adsl


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Column Header
Data Item
Codes
Derivation/Comments
Source 
data set
CANCER=0
AMT
Amount (in mg) of 
GSK2857916 given 
in first cycle 
AMT = AVAL when 
PARAMCD=ALTDOSE and AVISIT= 
CYCLE 1 DAY 1
adex
Q4AMT
Quartile of AMT
0,1,2,3
derived
Q5AMT
Quintile of AMT
0,1,2,3,4
derived
TOTAMT
Total dose received 
(mg)
TOTAMT = AVAL* WEIGHTBL;
Get AVAL for PARAMCD=CUMDOSE
adex,adsl
Q4TOTAMT
Quartile of TOTAMT
0,1,2,3
derived
Q5TOTAMT
Quintile of TOTAMT
0,1,2,3,4
derived
IDOSE
GSK2857916 initial 
cycle dose (mg/kg)
>0
IDOSE=adex.TRT01A; strip off units
adex
Q4IDOSE
Quartile of IDOSE
0,1,2,3
derived
Q5IDOSE
Quintile of IDOSE
0,1,2,3,4
derived
CMAX
First dose Cmax of 
ADC – Observed EOI 
on Cycle 1 (ng/mL)
popPK 
output
Q4CMAX
Quartile of CMAX
0,1,2,3
derived
Q5CMAX
Quintile of CMAX
0,1,2,3,4
derived
MMAFCMAX
First dose Cmax of 
MMAF – Observed 
EOI on Cycle 1 
(ng/mL)
popPK 
output
Q4MMAFCMAX
Quartile of 
MMAFCMAX
0,1,2,3
derived
Q5MMAFCMAX
Quintile of 
MMAFCMAX
0,1,2,3,4
derived
CTAU
First dose Ctau of 
ADC– Observed pre-
dose on Cycle 2
popPK 
output
Q4CTAU
Quartile of CTAU
0,1,2,3
derived
Q5CTAU
Quintile of CTAU
0,1,2,3,4
derived
AUC
First dose AUC(0-inf) 
of ADC (ug.day/mL)
First dose (mg)/Individual Clearance of 
ADC
popPK 
output
Q4AUC
Quartile of AUC
0,1,2,3
derived
Q5AUC
Quintile of AUC
0,1,2,3,4
derived
TOTAUC
Total AUC 
(ug.day/mL)
(Total dose received)/Individual Clearance 
of ADC
popPK 
output
Q4TOTAUC
Quartile of TOTAUC
0,1,2,3
derived
Q5TOTAUC
Quintile of TOTAUC
0,1,2,3,4
derived
MMAFAUC
First dose AUC(0-inf) 
of MMAF 
(ug.day/mL)
First dose (mg)/Individual Clearance of 
MMAF
popPK 
output
Q4MMAFAUC
Quartile of 
MMAFAUC
0,1,2,3
derived
Q5MMAFAUC
Quintile of 
MMAFAUC
0,1,2,3,4
derived
MMAFTOTAUC
Total AUC 
(ug.day/mL)
(Total dose received)/Individual Clearance 
of MMAF
popPK 
output 
Q4MMAFTOTAUC
Quartile of 
MMAFTOTAUC
0,1,2,3
derived
Q5MMAFTOTAUC
Quintile of 
MMAFTOTAUC
0,1,2,3,4
derived


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For efficacy
Column Header
Data Item
Codes
Derivation/Comments
Source data set
C
Exclusion 
identifier
Row 
Number
DORDM
Set to line/row number unless one or 
more of the following conditions are 
met, then set to code: 

DORDM: If DORD is missing 
adtte
STUDY
Study ID
1 = BMA117159
adsl
SUBJID
Subject identifier 
from source 
data 
SUBJID = SUBJID
adsl
ID
NONMEM 
subject identifier
Sequential subject identifier across 
studies after data is sorted by SUBJID. 
Starting with
derived
PFSCFLCD
PFS Censoring 
Flag Code
0 or 1
For PARAMCD=PFS_D, 
CNSR value is assigned to 
PFSCFLCD
0=Event
1=Censor
adtte
PFSD
PFS (Days)
For PARAMCD=PFS_D, 
AVAL value is assigned to PFSD
adtte
PFSM
PFS (Months)
For PARAMCD=PFS_M, 
AVAL value is assigned to PFSM
adtte
PFSY
PFS (Years)
For PARAMCD=PFS_D, 
(AVAL/365) value is assigned to PFSY
derived
TTRCFLCD
TTR Censoring 
Flag Code
0 or 1
For PARAMCD=TTR_D, 
Assign 1 to TTRCFLCD.
For subjects where TTR_D is missing, 
assign 0 to TTRCFLCD.
adtte
TTRD
TTR (Days)
For PARAMCD=TTR_D, 
AVAL value is assigned to TTRD.
For subjects where TTR_D is missing, 
assign PFSD to TTRD.
adtte
TTRM
TTR (Months)
For PARAMCD=TTR_M, 
AVAL value is assigned to TTRM.
For subjects where TTR_M is missing, 
assign PFSM to TTRM.
adtte
TTRY
TTR (Years)
For PARAMCD=TTR_D, 
(AVAL/365) value is assigned to TTRY.
For subjects where TTR_D is missing, 
assign PFSY to TTRY.
derived
DORCFLCD
DOR Censoring 
Flag Code
0 or 1
For PARAMCD=DOR_D, 
CNSR value is assigned to 
DORCFLCD
0=Event
1=Censor
Assign “.” for missing.
adtte
DORD
DOR (Days)
For PARAMCD=DOR_D, 
AVAL value is assigned to DORD.
For subjects where DOR_D is missing, 
assign “.”
adtte
P


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Column Header
Data Item
Codes
Derivation/Comments
Source data set
DORM
DOR (Months)
For PARAMCD=DOR_M, 
AVAL value is assigned to DORM.
For subjects where DOR_M is missing, 
assign “.”
adtte
DORY
DOR (Years)
For PARAMCD=DOR_D, 
(AVAL/365) value is assigned to DORY
For subjects where DOR_Y is missing, 
assign “.”
derived
ORDRESP
0,1,2,3,4,5,6 For PARAMCD=BCRSP, assign 
0 for PD
1 for SD
2 for MR
3 for PR
4 for VGPR
5 for CR
6 for sCR
adrs
MAXPRED
Obtain AVAL for 
PARAMCD=MAXPRED.
When AVAL is missing, MAXPRED = -
999 
adrs
RESPRATIO
Transform 
MAXRED to a 
ratio to baseline
RESPRATIO = 
max((100+MAXPRED)/100,0.001)

When MAXRED is missing, 
MAXRED = -999 and 
RESPRATIO= -99

When MAXRED is less than 
-100 e.g. -100.15, 
RESPRATIO = negative (It is 
negative but greater than -
8.99), then update 
RESPRATIO = 0.001 

When MAXRED is equal to -
100, RESPRATIO = 0, then 
update RESPRATIO = 0.001
adrs,derived
RSPTYP
Response Type
1,2,3
1 for Serum M-Protein
2 for Serum FLC
3 for Urine M-Protein
adrs
CUMAMTP
Cumulative 
dose to PFS 
(mg)
For progression that occurred on 
dosing days, the dose on the 
progression day was not included in 
the cumulative dose calculation. 
adex, adtte
Q4CUMAMTP
Quartile of 
CUMAMTP
0,1,2,3
derived
Q5CUMAMT
Quintile of 
CUMAMTP
0,1,2,3,4
derived
CUMAUCP
Cumulative AUC 
to progression 
(ug.day/mL)
(Cumulative dose to 
progression)/Individual Clearance of 
ADC
popPK output, 
adtte
Q4CUMAUCP
Quartile of 
CUMAUCP
0,1,2,3
derived
Q5CUMAUCP
Quintile of 
0,1,2,3,4
derived


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Column Header
Data Item
Codes
Derivation/Comments
Source data set
CUMAUCP
TAAUCP 
Time-average 
AUC till 
progression 
(AUC/day)
The area under the plasma ADC 
concentration–time curve (AUC) per 
day (AUC/day) will be derived for each 
patient using the available ADC dosing 
information, individual patient oral 
clearance (CL/F) values from the 
population pharmacokinetic model, and 
the time to the occurrence of the PFS
popPK output, 
adtte
Q4TAAUCP
Quartile of 
TAAUCP
0,1,2,3
derived
Q5TAAUCP
Quintile of 
TAAUCP
0,1,2,3,4
derived
CUMAMTR
Cumulative 
dose to 
Response (mg)
For response that occurred on dosing 
days, the dose on the response day 
was not included in the cumulative 
dose calculation. 
adex, adtte
Q4CUMTAMTR
Quartile of 
CUMAMTR
0,1,2,3
derived
Q5CUMTAMTR
Quintile of 
CUMAMTR
0,1,2,3,4
derived
CUMAUCR
Cumulative AUC 
to response 
(ug.day/mL)
(Cumulative dose to 
response)/Individual Clearance of ADC
adex, adtte, 
popPK output
Q4CUMAUCR
Quartile of 
CUMAUCR
0,1,2,3
derived
Q5CUMAUCR
Quintile of 
CUMAUCR
0,1,2,3,4
derived
TAAUCR 
Time-average 
AUC till 
response 
(AUC/day)
The area under the plasma ADC 
concentration–time curve (AUC) per 
day (AUC/day) will be derived for each 
patient using the available ADC dosing 
information, individual patient oral 
clearance (CL/F) values from the 
population pharmacokinetic model, and 
the time to the occurrence of the 
response
popPK output, 
adtte
Q4TAAUCR
Quartile of 
TAAUCR
0,1,2,3
derived
Q5TAAUCR
Quintile of 
TAAUCR
0,1,2,3,4
derived
CUMAMTD
Cumulative 
dose to DOR 
(mg)
For DOR that occurred on dosing days, 
the dose on the DOR day was not 
included in the cumulative dose 
calculation. 
adex, adtte
Q4CUMTAMTD
Quartile of 
CUMAMTD
0,1,2,3
derived
Q5CUMTAMTD
Quintile of 
CUMAMTD
0,1,2,3,4
derived
CUMAUCD
Cumulative AUC 
to DOR 
(ug.day/mL)
(Cumulative dose to DOR)/Individual 
Clearance of ADC
adex,adtte,popPK 
output
Q4CUMAUCD
Quartile of 
CUMAUCD
0,1,2,3
derived


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Column Header
Data Item
Codes
Derivation/Comments
Source data set
Q5CUMAUCD
Quintile of 
CUMAUCD
0,1,2,3,4
derived
TAAUCD
Time-average 
AUC till DOR 
(AUC/day)
The area under the plasma ADC 
concentration–time curve (AUC) per 
day (AUC/day) will be derived for each 
patient using the available ADC dosing 
information, individual patient oral 
clearance (CL/F) values from the 
population pharmacokinetic model, and 
the time to the occurrence of the 
duration of response
adtte, popPK 
output
Q4TAAUCD
Quartile of 
TAAUCD
0,1,2,3
derived
Q5TAAUCD
Quintile of 
TAAUCD
0,1,2,3,4
derived
CANCER
Cancer type
0 or 1
0=Multiple Myeloma, 1=BCMA positive 
Lymphomas
If TRT01AN = 12, then CANCER=1, 
else CANCER=0
adsl
AMT
Amount (in mg) 
of GSK2857916 
given in first 
cycle 
AMT = AVAL when 
PARAMCD=ALTDOSE and AVISIT= 
CYCLE 1 DAY 1
adex
Q4AMT
Quartile of AMT
0,1,2,3
derived
Q5AMT
Quintile of AMT
0,1,2,3,4
derived
TOTAMT
Total dose 
received (mg)
TOTAMT = AVAL* WEIGHTBL;
Get AVAL for PARAMCD=CUMDOSE
adex,adsl
Q4TOTAMT
Quartile of 
TOTAMT
0,1,2,3
derived
Q5TOTAMT
Quintile of 
TOTAMT
0,1,2,3,4
derived
IDOSE
GSK2857916 
initial cycle dose 
(mg/kg)
>0
IDOSE=adex.TRT01A; strip off units
adex
Q4IDOSE
Quartile of 
IDOSE
0,1,2,3
derived
Q5IDOSE
Quintile of 
IDOSE
0,1,2,3,4
derived
CMAX
First dose Cmax 
of ADC –
Observed EOI 
on Cycle 1 
(ng/mL)
popPK output
Q4CMAX
Quartile of 
CMAX
0,1,2,3
derived
Q5CMAX
Quintile of 
CMAX
0,1,2,3,4
derived
MMAFCMAX
First dose Cmax 
of MMAF –
Observed EOI 
on Cycle 1 
(ng/mL)
popPK output
Q4MMAFCMAX
Quartile of 
MMAFCMAX
0,1,2,3
derived
Q5MMAFCMAX
Quintile of 
0,1,2,3,4
derived


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Column Header
Data Item
Codes
Derivation/Comments
Source data set
MMAFCMAX
CTAU
First dose Ctau of 
ADC– Observed 
pre-dose on 
Cycle 2
popPK output
Q4CTAU
Quartile of 
CTAU
0,1,2,3
derived
Q5CTAU
Quintile of 
CTAU
0,1,2,3,4
derived
AUC
First dose 
AUC(0-inf) of 
ADC 
(ug.day/mL)
First dose (mg)/Individual Clearance of 
ADC
popPK output
Q4AUC
Quartile of AUC
0,1,2,3
derived
Q5AUC
Quintile of AUC
0,1,2,3,4
derived
TOTAUC
Total AUC 
(ug.day/mL)
(Total dose received)/Individual 
Clearance of ADC
popPK output
Q4TOTAUC
Quartile of 
TOTAUC
0,1,2,3
derived
Q5TOTAUC
Quintile of 
TOTAUC
0,1,2,3,4
derived
MMAFAUC
First dose 
AUC(0-inf) of 
MMAF 
(ug.day/mL)
First dose (mg)/Individual Clearance of 
MMAF
popPK output
Q4MMAFAUC
Quartile of 
MMAFAUC
0,1,2,3
derived
Q5MMAFAUC
Quintile of 
MMAFAUC
0,1,2,3,4
derived
MMAFTOTAUC
Total AUC 
(ug.day/mL)
(Total dose received)/Individual 
Clearance of MMAF
popPK output 
Q4MMAFTOTAUC
Quartile of 
MMAFTOTAUC
0,1,2,3
derived
Q5MMAFTOTAUC
Quintile of 
MMAFTOTAUC
0,1,2,3,4
derived
16.10.2.
Pharmacokinetic / Pharmacodynamic Methodology
The primary goal of this analysis is to characterize the 
pharmacokinetic/pharmacodynamic relationships for GSK2857916 administered IV in 
subjects with multiple myeloma.  In these analyses, drug plasma concentration (or 
pharmacokinetic parameter) data and pharmacodynamic data will be subjected to 
nonlinear mixed effects modelling using suitable software.  The influence of subject 
demographics and baseline characteristics, including disease activity, in this population 
may be investigated.  This analysis will be performed by CPMS and reported separately.
16.10.2.1.
PD Model of sBCMA Binding
Soluble and complex BCMA levels will be log-transformed and described using a 
conventional linear mixed effects model and planned time for Cycle 1. Ratio to pre-dose 
Cycle 1 will be estimated.  If data permit, parameter values will be estimated. In addition, 
prediction of free sBCMA data using a quasi-steady-state approximation (QSSA) PK/PD 
reaction binding model may be conducted without parameter estimation.


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16.10.2.2. Exposure-Response Analyses
16.10.2.2.1.
Corneal Toxicity
Presence or absence of corneal toxicity will be described using a conventional logistic 
regression model for both Grade 1 and Grade 2 toxicity. Time to first corneal toxicity 
will be explored using Kaplan Meier plots with exposure subdivided into quartiles and 
quintiles. Severity of corneal toxicity will be analyzed using an ordered logistic 
regression model assuming Grades 0 (no toxicity), 1, 2 and 3, with exposure subdivided 
into quartiles and quintiles.
16.10.2.2.2.
Clinical Response
Presence or absence of clinical response will be described using a conventional logistic 
regression model. Time to response will be explored using Kaplan Meier plots with 
exposure subdivided into quartiles and quintiles.
PFS will be explored using Kaplan Meier plots with exposure subdivided into quartiles 
and quintiles and occurrence of progression may also be described using a conventional 
logistic regression model.
Duration of response will be explored using Kaplan Meier plots with exposure 
subdivided into quartiles and quintiles. 
Best clinical response will be analyzed using an ordered logistic regression, with 
response categorized from 0 (progressive disease) to 6 (stringent complete response). 
Exposure will be treated as a categorical variable subdivided into quartiles and quintiles.  
In the ordered logistic regression analyses, the use of categorical measures of exposure in 
lieu of continuous variables will allow for non-parametric descriptions of response 
functions.
Best clinical response as assessed by maximum reduction in M-protein or FLC will be 
analyzed by exposure (continuous and/or by quartile and quintile of exposure).


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16.11.
Appendix 11: Abbreviations & Trade Marks
16.11.1.
Abbreviations
Abbreviation
Description
ADaM
Analysis Data Model
AE
Adverse Event
AIC
Akaike's Information Criteria
A&R
Analysis and Reporting 
CDISC
Clinical Data Interchange Standards Consortium
CI
Confidence Interval
CPMS
Clinical Pharmacology Modelling & Simulation
CS
Clinical Statistics
CSR
Clinical Study Report
CTR
Clinical Trial Register
CVb / CVw
Coefficient of Variation (Between) / Coefficient of Variation (Within)
DBF
Database Freeze
DBR
Database Release
BCMA
B cell maturation antigen
BCVA
Best corrected visual acuity
CBR
Clinical benefit rate
CDISC
Clinical Data Interchange Standards Consortium
CI
Confidence interval
CK-MB
Creatine kinase MB-isoenzyme
CL
Clearance
Cmax
Maximum plasma drug concentration
CPMS
Clinical Pharmacology Modeling and Simulation
CR
Complete response
CRM
Continual Reassessment Method
Ctrough
Trough plasma concentration
Cys-mcMMAF
cys Monomethyl auristatin F 
DLT
Dose limiting toxicity
DOB
Date of Birth
DOR
Duration of response
DP
Decimal Places
eDiary
Electronic Diary
ECOG
Eastern Cooperative Oncology Group
EOI
End of infusion
eCRF
Electronic Case Record Form
EMA
European Medicines Agency
FACTS
Fixed and adapted clinical trials simulator
FDA
Food and Drug Administration
FDAAA
Food and Drug Administration Clinical Results Disclosure Requirements
FLC
Free light chain
FTIH
First time in human
GSK
GlaxoSmithKline


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Abbreviation
Description
IA
Interim Analysis
ICH
International Conference on Harmonization
IDMC
Independent Data Monitoring Committee 
IDSL
Integrated Data Standards Library
IMMS
International Modules Management System
IP
Investigational Product
ITT
Intent-To-Treat
LDH
Lactate dehydrogenase
MMRM
Mixed Model Repeated Measures
MM
Multiple Myeloma
MMAF
Monomethyl auristatin F
MR
Minimal response
MTD
Maximum Tolerated Dose
NCI-CTCAE
National Cancer Institute – Common Terminology Criteria for Adverse Events
N-CRM
A modification of the Continual Reassessment Method (CRM) proposed by 
Neuenschwander et al.
NEI-VFQ-25
National Eye Institute Visual Functioning Questionnaire - 25
NONMEM
Non linear mixed effects modelling
ORR
Overall response rate
OS
Overall survival
OSDI
Ocular Surface Disease Index
PCI
Potential Clinical Importance 
PD
Pharmacodynamic
PDMP
Protocol Deviation Management Plan
PET
Probability of early termination
PFS
Progression-free survival
PK
Pharmacokinetic
PP
Per Protocol
PR
Partial response
PopPK
Population PK
QC
Quality Control
QoL
Quality of life
QTcF
Frederica’s QT Interval Corrected for Heart Rate
QTcB
Bazett’s QT Interval Corrected for Heart Rate
RAP
Reporting & Analysis Plan
RAMOS
Randomization & Medication Ordering System 
REML
Restricted maximum likelihood
Ro
Observed accumulation ratio
RP2
Recommended Phase 2 
SAC
Statistical Analysis Complete
SAE
Serious adverse event
sBCMA
Soluble B-cell maturation antigen
sCR
Stringent complete response
SD
Stable disease
SDSP
Study Data Standardization Plan


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Abbreviation
Description
SDTM
Study Data Tabulation Model
SOI
Start of infusion
SPEP
Serum protein electrophoresis
SOP
Standard Operation Procedure
t½ 
Half-life
TA
Therapeutic Area
TFL
Tables, Figures & Listings 
Tmax
Time to maximum drug concentration
TTBR
Time to best response
TTP
Time to progression
TTR
Time to response
ULN
Upper limit of normal
UPEP
Urine protein electrophoresis
VGPR
Very good partial response
16.11.2.
Trademarks
Trademarks of the GlaxoSmithKline 
Group of Companies
Trademarks not owned by the 
GlaxoSmithKline Group of Companies
NONE
FACTS
NONMEM
SAS
WinNonlin


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16.12.
Appendix 12: List of Data Displays
16.12.1.
Data Display Numbering
The following numbering will be applied for RAP generated displays:
Section
Tables
Figures
Study Population
1.0010 to 1.xxxx
11.0010 to 11.xxxx
Efficacy
2.0010 to 2.xxxx
12.0010 to 12.xxxx
Safety
3.0010 to 3.xxxx
13.0010 to 13.xxxx
Pharmacokinetic
4.0010 to 4.xxxx
14.0010 to 14.xxxx
Population Pharmacokinetic (PopPK)
5.0010 to 5.xxxx
15.0010 to 15.xxxx
Pharmacodynamic and / or Biomarker
6.0010 to 6.xxxx
16.0010 to 16.xxxx
Pharmacokinetic / Pharmacodynamic
7.0010 to 7.xxxx
17.0010 to 17.xxxx
Section
Listings
ICH Listings
1.0010 to 1.xxxx
Other Listings
30.0010 to 30.xxxx
16.12.2.
Mock Example Shell Referencing
Non IDSL specifications will be referenced as indicated and if required example mock-up 
displays provided in Appendix 13: Example Mock Shells for Data Displays.
Section
Figure
Table
Listing
Study Population
POP_Fn
POP_Tn
POP_Ln
Efficacy
EFF_Fn
EFF_Tn
EFF_Ln
Safety
SAFE_Fn
SAFE_Tn
SAFE_Ln
Pharmacokinetic
PK_Fn
PK_Tn
PK_Ln
Population Pharmacokinetic (PopPK)
POPPK_Fn
POPPK_Tn
POPPK_Ln
Pharmacodynamic and / or Biomarker
PD_Fn
PD_Tn
PD_Ln
Pharmacokinetic / Pharmacodynamic
PKPD_Fn
PKPD_Tn
PK/PD_Ln
NOTES: 

Non-Standard displays are indicated in the ‘IDSL /  Example Shell’ or ‘Programming Notes’ column as ‘[Non-
Standard] + Reference.’
16.12.3.
Deliverables
Delivery [Priority] [1]
Description
DS [X]
During Study
DE [X]
Dose Escalation
IA SAC [X]
Interim Analysis Statistical Analysis Complete
SAC [X]
Final Statistical Analysis Complete
NOTES: 
1.
Indicates priority (i.e. order) in which displays will be generated for the reporting effort.


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16.12.4.
Study Population Tables
Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Subject Disposition
1.0010
All Treated
ES8
Summary of Subject Status and Reason for Study Withdrawal 
(Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [1]
1.0011
All Treated
ES8
Summary of Subject Status and Reason for Study Withdrawal 
(Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0012
All Treated
ES8
Summary of Subject Status and Reason for Study Withdrawal 
(All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0013
All Treated
ES8
Summary of Subject Status and Reason for Study Withdrawal 
(Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
1.0020
All Treated
SD4
Summary of Treatment Status and Reasons for Discontinuation 
of Study Treatment (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0021
All Treated
SD4
Summary of Treatment Status and Reasons for Discontinuation 
of Study Treatment (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0022
All Treated
SD4
Summary of Treatment Status and Reasons for Discontinuation 
of Study Treatment (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0023
All Treated
SD4
Summary of Treatment Status and Reasons for Discontinuation 
of Study Treatment (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
1.0550
Screened
ES6
Summary of Screening Status and Reasons for Screen Failure 
(Part 1)
SAC [A]
1.0551
Screened
ES6
Summary of Screening Status and Reasons for Screen Failure 
(Part 2 MM)
SAC [A]
1.0552
Screened
ES6
Summary of Screening Status and Reasons for Screen Failure 
(All Treated MM)
SAC [A]


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Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0553
Screened
ES6
Summary of Screening Status and Reasons for Screen Failure 
(Part 2 NHL)
SAC
1.0030
Enrolled
NS1
Summary of Number of Participant by Country and Site ID (MM)
Include columns: No Treatment, 
Part 1, Part 2 MM, All Treated MM, 
Total column will be the subjects 
enrolled to MM cohort. Add a 
footnote: This summary is based on 
all subjects enrolled into multiple 
myeloma cohorts.
SAC [A]
1.0031
Enrolled
NS1
Summary of Number of Participant by Country and Site ID (NHL)
Include columns: No Treatment, 
Part 2 NHL, Total column will be the 
subjects enrolled to NHL cohort. 
Add a footnote: This summary is 
based on all subjects enrolled into 
lymphoma cohorts.
SAC
1.0050
All Treated
IE1
Summary of Inclusion/Exclusion Criteria Deviations (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0051
All Treated
IE1
Summary of Inclusion/Exclusion Criteria Deviations (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0052
All Treated
IE1
Summary of Inclusion/Exclusion Criteria Deviations (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0053
All Treated
IE1
Summary of Inclusion/Exclusion Criteria Deviations (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC


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Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Protocol Deviation
1.0040
All Treated
DV1
Summary of Important Protocol Deviations (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0041
All Treated
DV1
Summary of Important Protocol Deviations (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0042
All Treated
DV1
Summary of Important Protocol Deviations (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0043
All Treated
DV1
Summary of Important Protocol Deviations (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
Population Analysed
1.0060
Enrolled
SP1
Summary of Study Populations (MM)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total). This 
table is based on subjects enrolled 
to MM, we do not have screen 
failure data, hence no screened 
population. For columns, include No 
Treatment, No Treatment for Part 1, 
No Treatment for Part 2 MM, Dose 
levels in part 1, All Treated in Part 
1, All Treated in Part 2, All Treated 
and Total. 
Rows: include Enrolled, Part 1, Part 
2 MM, All Treated MM, DLT 
Evaluable, PK, PD
SAC [A]
1.0061
Enrolled
SP1
Summary of Study Populations (NHL)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). This table is 
SAC


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Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
based on subjects enrolled to NHL, 
we do not have screen failure data, 
hence no screened population. For 
columns, include No Treatment, All 
Treated and Total. 
Rows: include Enrolled, Part 2 NHL, 
PK, PD
1.0430
Enrolled
SP2A
Summary of the Exclusions from the Part 1 Population
SAC [A]
1.0431
Enrolled
SP2A
Summary of the Exclusions from the Part 2 MM Population
SAC [A]
1.0432
Enrolled
SP2A
Summary of the Exclusions from the All Treated MM Population
SAC [A]
1.0433
Enrolled
SP2A
Summary of the Exclusions from the Part 2 NHL Population
SAC [A]
1.0434
Enrolled
SP2A
Summary of the Exclusions from the All Treated Population
SAC
1.04354
Enrolled
SP2A
Summary of the Exclusions from the DLT Evaluable Population 
SAC [A]
1.0436
Enrolled
SP2A
Summary of the Exclusions from the Pharmacokinetic (PK) 
Population 
SAC [A]
1.0437
Enrolled
SP2A
Summary of the Exclusions from the Pharmacodynamic (PD) 
Population 
SAC [A]
Demographic and Baseline Characteristics
1.0070
All Treated
DM1
Summary of Demographic Characteristics (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0071
All Treated
DM1
Summary of Demographic Characteristics (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0072
All Treated
DM1
Summary of Demographic Characteristics (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]


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Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0073
All Treated
DM1
Summary of Demographic Characteristics (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
1.0290
Enrolled
DM11
Summary of Age Ranges (MM)
Include columns "No Treatment", 
"Part 1", "Part 2 MM", "All Treated 
MM", "Total"
SAC [1]
1.0291
Enrolled
DM11
Summary of Age Ranges (NHL)
Include columns "No Treatment", 
"Part 2 NHL", "Total"
SAC
1.0080
All Treated
DM5
Summary of Race and Racial Combinations (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0081
All Treated
DM5
Summary of Race and Racial Combinations (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0082
All Treated
DM5
Summary of Race and Racial Combinations (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0083
All Treated
DM5
Summary of Race and Racial Combinations (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
1.0090
All Treated
DM6
Summary of Race and Racial Combination Details (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0091
All Treated
DM6
Summary of Race and Racial Combination Details (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0092
All Treated
DM6
Summary of Race and Racial Combination Details (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0093
All Treated
DM6
Summary of Race and Racial Combination Details (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC


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Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Prior and Concomitant Medications
1.0190
All Treated
MH1
Summary of Past Medical Conditions (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0191
All Treated
MH1
Summary of Past Medical Conditions (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0192
All Treated
MH1
Summary of Past Medical Conditions (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0193
All Treated
MH1
Summary of Past Medical Conditions (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
1.0200
All Treated
MH1
Summary of Current Medical Conditions (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0201
All Treated
MH1
Summary of Current Medical Conditions (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0202
All Treated
MH1
Summary of Current Medical Conditions (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0203
All Treated
MH1
Summary of Current Medical Conditions (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
1.0210
All Treated
CM8
Summary of Concomitant Medications  (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0211
All Treated
CM8
Summary of Concomitant Medications (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0212
All Treated
CM8
Summary of Concomitant Medications (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0213
All Treated
CM8
Summary of Concomitant Medications (Part 2 NHL)
Report for: Part 2 NHL, 
SAC


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Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
(Summarize: only for 3.4 NHL).
1.0380
All Treated
CM1
Summary of Prophylactic Medication for Infusion-Related 
Reactions by Drug Class and Drug Name (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). Please 
replace ATC Level 1 by ‘Drug Class’ 
and ‘Ingredient’ by ‘Drug’. Replace 
the footnote as “Subjects may be 
included in more than one category 
for ‘Drug Class' and ‘Drug'.
SAC [A]
1.0381
All Treated
CM1
Summary of Prophylactic Medication for Infusion-Related 
Reactions by Drug Class and Drug Name (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Please replace 
ATC Level 1 by ‘Drug Class’ and 
‘Ingredient’ by ‘Drug’. Replace the 
footnote as “Subjects may be 
included in more than one category 
for ‘Drug Class' and ‘Drug'.
SAC [A]
1.0382
All Treated
CM1
Summary of Prophylactic Medication for Infusion-Related 
Reactions by Drug Class and Drug Name (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Please replace 
ATC Level 1 by ‘Drug Class’ and 
‘Ingredient’ by ‘Drug’. Replace the 
footnote as “Subjects may be 
included in more than one category 
for ‘Drug Class' and ‘Drug'.
SAC [A]
1.0383
All Treated
CM1
Summary of Prophylactic Medication for Infusion-Related 
Reactions by Drug Class and Drug Name (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
Please replace ATC Level 1 by 
‘Drug Class’ and ‘Ingredient’ by 
‘Drug’. Replace the footnote as 
“Subjects may be included in more 
SAC


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Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
than one category for ‘Drug Class' 
and ‘Drug'.
1.0510
All Treated
OSP2
Summary of Prior Cancer and Non-Cancer Related Surgical 
Procedures (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). If the 
CRF does not have any coded 
procedures and collection of 
surgeries is restricted to prior 
cancer related surgeries, then a 
summary is not necessary as the 
number and percent of subjects with 
surgeries will be provided in the 
anticancer therapy display (see 
Example AC1).  Otherwise a 
simplified version of the summary 
can be utilized if appropriate (see 
example OSP2).  
SAC [A]
1.0511
All Treated
OSP2
Summary of Prior Cancer and Non-Cancer Related Surgical 
Procedures (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0512
All Treated
OSP2
Summary of Prior Cancer and Non-Cancer Related Surgical 
Procedures (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0513
All Treated
OSP2
Summary of Prior Cancer and Non-Cancer Related Surgical 
Procedures (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
Exposure and Treatment Compliance
1.0240
All Treated
OEX5
Summary of Exposure to GSK2857916 (Part 1)
Report for population: Part 1, 
(Summarize: by ascending dose 
level, Total).
Do not need "Dose Intensity " 
SAC [A]


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Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
section. Use 4, <4, >4 cycles
1.0241
All Treated
OEX5
Summary of Exposure to GSK2857916 (Part 2 MM)
Report for population: Part 2 MM, 
(Summarize: only for 3.4 MM). 
Do not need "Dose Intensity " 
section. Use 4, <4, >4 cycles
SAC [A]
1.0242
All Treated
OEX5
Summary of Exposure to GSK2857916 (All Treated MM)
Report for population: All Treated 
MM, (Summarize: Total)
Do not need "Dose Intensity " 
section. Use 4, <4, >4 cycles
SAC [A]
1.0243
All Treated
OEX5
Summary of Exposure to GSK2857916 (Part 2 NHL)
Report for population: 3.4 NHL, 
(Summarize: Total)
Do not need "Dose Intensity " 
section. Use 4, <4, >4 cycles
SAC
1.0230
All Treated
OEX6
Summary of Dose Intensity of GSK2857916 by Cycle (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total). Dose 
Intensity(mg/kg/cycle)
SAC [A]
1.0231
All Treated
OEX6
Summary of Dose Intensity of GSK2857916 by Cycle (Part 2 
MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Dose 
Intensity(mg/kg/cycle)
SAC [A]
1.0232
All Treated
OEX6
Summary of Dose Intensity of GSK2857916 by Cycle (All 
Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Dose 
Intensity(mg/kg/cycle)
SAC [A]
1.0233
All Treated
OEX6
Summary of Dose Intensity of GSK2857916 by Cycle (Part 2 
NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL). 
Dose Intensity(mg/kg/cycle)
SAC


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Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0250
All Treated
ODMOD
1
Summary of Dose Reductions of GSK2857916 (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0251
All Treated
ODMOD
1
Summary of Dose Reductions of GSK2857916 (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0252
All Treated
ODMOD
1
Summary of Dose Reductions of GSK2857916 (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0253
All Treated
ODMOD
1
Summary of Dose Reductions of GSK2857916 (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
1.0260
All Treated
ODMOD
3
Summary of Dose Delays of GSK2857916 (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0261
All Treated
ODMOD
3
Summary of Dose Delays of GSK2857916 (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0262
All Treated
ODMOD
3
Summary of Dose Delays of GSK2857916 (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0263
All Treated
ODMOD
3
Summary of Dose Delays of GSK2857916 (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
1.0270
All Treated
ODMOD
5
Summary of Primary Reason for Dose Reductions of 
GSK2857916 by Cycle (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0271
All Treated
ODMOD
5
Summary of Primary Reason for Dose Reductions of 
GSK2857916 by Cycle (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0272
All Treated
ODMOD
5
Summary of Primary Reason for Dose Reductions of 
GSK2857916 by Cycle (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0273
All Treated
ODMOD
5
Summary of Primary Reason for Dose Reductions of 
GSK2857916 by Cycle (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC


CONFIDENTIAL
BMA117159
133
Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0280
All Treated
ODMOD
6
Summary of Primary Reason for Dose Delays of GSK2857916 
by Cycle (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0281
All Treated
ODMOD
6
Summary of Primary Reason for Dose Delays of GSK2857916 
by Cycle (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0282
All Treated
ODMOD
6
Summary of Primary Reason for Dose Delays of GSK2857916 
by Cycle (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0283
All Treated
ODMOD
6
Summary of Primary Reason for Dose Delays of GSK2857916 
by Cycle (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
Disease Characteristics
1.0100
All Treated
DC2
Summary of Disease Characteristics at Screening (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total). 
Summarize Stage (I, II, III, 
Unknown, Missing), 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, IgG, Other, Missing)
SAC [A]
1.0101
All Treated
DC2
Summary of Disease Characteristics at Screening (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Summarize 
categories as defined in Table 
1,0100.
SAC [A]


CONFIDENTIAL
BMA117159
134
Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0102
All Treated
DC2
Summary of Disease Characteristics at Screening (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total). Summarize 
categories as defined in Table 
1,0100.
SAC [A]
1.0103
All Treated
DC2
Summary of Disease Characteristics at Screening (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
1.0110
All Treated
POP_T1
Summary of Genetic Characteristics at Screening (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0111
All Treated
POP_T1
Summary of Genetic Characteristics at Screening (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0112
All Treated
POP_T1
Summary of Genetic Characteristics at Screening (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0300
All Treated
DC1
Summary of Disease Characteristics at Initial Diagnosis (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total). 
Include alll optional columns.
SAC [A]
1.0301
All Treated
DC1
Summary of Disease Characteristics at Initial Diagnosis (Part 2 
MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Include all optional 
columns.
SAC [A]
1.0302
All Treated
DC1
Summary of Disease Characteristics at Initial Diagnosis (All 
Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Include all 
optional columns.
SAC [A]
1.0303
All Treated
DC1
Summary of Disease Characteristics at Initial Diagnosis (Part 2 
NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL). 
Include all optional columns.
SAC


CONFIDENTIAL
BMA117159
135
Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0390
All Treated
POP_T2
Summary of Cytogenetics Risk at Screening (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0391
All Treated
POP_T2
Summary of Cytogenetics Risk at Screening (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0392
All Treated
POP_T2
Summary of Cytogenetics Risk at Screening (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
Prior and Follow-up Anti-Cancer Therapy
1.0120
All Treated
AC1
Summary of Prior Anti-Cancer Therapy (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0121
All Treated
AC1
Summary of Prior Anti-Cancer Therapy (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0122
All Treated
AC1
Summary of Prior Anti-Cancer Therapy (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0123
All Treated
AC1
Summary of Prior Anti-Cancer Therapy (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
1.0130
All Treated
CM8
Summary of Prior Dictionary Coded Anti-Cancer Therapy (Part 
1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0131
All Treated
CM8
Summary of Prior Dictionary Coded Anti-Cancer Therapy (Part 2 
MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0132
All Treated
CM8
Summary of Prior Dictionary Coded Anti-Cancer Therapy (All 
Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0133
All Treated
CM8
Summary of Prior Dictionary Coded Anti-Cancer Therapy (Part 2 
NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC


CONFIDENTIAL
BMA117159
136
Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0140
All Treated
POP_T3
Summary of Prior Anti-Cancer Therapy by Drug Class of Agents 
(Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0141
All Treated
POP_T3
Summary of Prior Anti-Cancer Therapy by Drug Class of Agents 
(Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0142
All Treated
POP_T3
Summary of Prior Anti-Cancer Therapy by Drug Class of Agents 
(All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0150
All Treated
POP_T4
Summary of Subjects Refractory to Prior Anti-Cancer Therapy 
by Drug Class of Agents (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0151
All Treated
POP_T4
Summary of Subjects Refractory to Prior Anti-Cancer Therapy 
by Drug Class of Agents (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0152
All Treated
POP_T4
Summary of Subjects Refractory to Prior Anti-Cancer Therapy 
by Drug Class of Agents (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0160
All Treated
AC3
Summary of Number of Prior Anti-Cancer Therapy Regimens 
(Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total). 
Therapies should be sorted in 
highest to lowest incidence. Include 
radio therapy and surgical 
procedures.
SAC [A]
1.0161
All Treated
AC3
Summary of Number of Prior Anti-Cancer Therapy Regimens 
(Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Therapies should 
be sorted in highest to lowest 
incidence. Include radio therapy and 
surgical procedures.
SAC [A]
1.0162
All Treated
AC3
Summary of Number of Prior Anti-Cancer Therapy Regimens 
(All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Therapies 
should be sorted in highest to 
SAC [A]


CONFIDENTIAL
BMA117159
137
Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
lowest incidence. Include radio 
therapy and surgical procedures.
1.0163
All Treated
AC3
Summary of Number of Prior Anti-Cancer Therapy Regimens 
(Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL). 
Therapies should be sorted in 
highest to lowest incidence. Include 
radio therapy and surgical 
procedures.
SAC
1.0170
All Treated
AC4
Summary of Best Response to Most Recent Prior Anti-Cancer 
Therapy (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total). Only 
use last therapy prior to starting 
study, 
SAC [A]
1.0171
All Treated
AC4
Summary of Best Response to Most Recent Prior Anti-Cancer 
Therapy (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Only use last 
therapy prior to starting study
SAC [A]
1.0172
All Treated
AC4
Summary of Best Response to Most Recent Prior Anti-Cancer 
Therapy (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Only use last 
therapy prior to starting study
SAC [A]
1.0173
All Treated
AC4
Summary of Best Response to Most Recent Prior Anti-Cancer 
Therapy (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
1.0470
All Treated
FAC1
Summary of Follow-Up Anti-Cancer Therapy (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0471
All Treated
FAC1
Summary of Follow-Up Anti-Cancer Therapy (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0472
All Treated
FAC1
Summary of Follow-Up Anti-Cancer Therapy (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]


CONFIDENTIAL
BMA117159
138
Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0473
All Treated
FAC1
Summary of Follow-Up Anti-Cancer Therapy (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
Duration of Follow-up 
1.0310
All Treated
FAC2
Summary of Duration of Follow-up (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total). 
Include all optional columns.
SAC [A]
1.0311
All Treated
FAC2
Summary of Duration of Follow-up (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Include all optional 
columns.
SAC [A]
1.0312
All Treated
FAC2
Summary of Duration of Follow-up (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Include al 
optional columns.
SAC [A]
1.0313
All Treated
FAC2
Summary of Duration of Follow-up (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL). 
Include all optional columns.
SAC
1.0400
All Treated
FAC2
Summary of Duration of Follow-up for Subjects with Prior 
Daratumumab Treatment and Refractory to Both IMiDs and 
Proteasomes Inhibitors (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0401
All Treated
FAC2
Summary of Duration of Follow-up for Subjects with Prior 
Daratumumab Treatment and Refractory to Both IMiDs and 
Proteasomes Inhibitors (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0402
All Treated
FAC2
Summary of Duration of Follow-up for Subjects with Prior 
Daratumumab Treatment and Refractory to Both IMiDs and 
Proteasomes Inhibitors (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0410
All Treated
FAC2
Summary of Duration of Follow-up for Subjects without Prior 
Report for:  Part 1, (Summarize: by 
SAC [A]


CONFIDENTIAL
BMA117159
139
Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Daratumumab Treatment (Part 1)
ascending dose level, Total).
1.0411
All Treated
FAC2
Summary of Duration of Follow-up for Subjects without Prior 
Daratumumab Treatment (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0412
All Treated
FAC2
Summary of Duration of Follow-up for Subjects without Prior 
Daratumumab Treatment (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0420
All Treated
FAC2
Summary of Duration of Follow-up for Subjects Refractory to 
Both IMiDs and Proteasomes Inhibitors (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0421
All Treated
FAC2
Summary of Duration of Follow-up for Subjects Refractory to 
Both IMiDs and Proteasomes Inhibitors (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0422
All Treated
FAC2
Summary of Duration of Follow-up for Subjects Refractory to 
Both IMiDs and Proteasomes Inhibitors (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
Blood and Blood Supportive Care Products
1.0480
All Treated
BP1A
Summary of Blood Products (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0481
All Treated
BP1A
Summary of Blood Products (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]
1.0482
All Treated
BP1A
Summary of Blood Products (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0483
All Treated
BP1A
Summary of Blood Products (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
1.0490
All Treated
BP1C
Summary of Blood Supportive Care Products (Part 1)
Report for:  Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
1.0491
All Treated
BP1C
Summary of Blood Supportive Care Products (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM).
SAC [A]


CONFIDENTIAL
BMA117159
140
Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0492
All Treated
BP1C
Summary of Blood Supportive Care Products (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
1.0493
All Treated
BP1C
Summary of Blood Supportive Care Products (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
SAC
Substance Use
1.0500
All Treated
SU1
Summary of Substance Use (Part 1)
Report for
:  Part 1, (Summarize: by ascending 
dose level, Total). All substance 
collected in eCRF
SAC [A]
1.0501
All Treated
SU1
Summary of Substance Use (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). All substance 
collected in eCRF
SAC [A]
1.0502
All Treated
SU1
Summary of Substance Use (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). All substance 
colleced in eCRF
SAC [A]
1.0503
All Treated
SU1
Summary of Substance Use (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL). All 
substance colleced in eCRF
SAC
NOTES: 
A. Indicates which displays will be generated for the reporting effort for multiple myeloma


CONFIDENTIAL
BMA117159
141
16.12.5.
Study Population Figures
Study Population: Figures
No.
Population
IDSL /  
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Exposure
11.0020
All Treated
POP_F2
Plot of Dose Reduction of GSK2857916 by Cycle (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Combine 1.9 mg/kg and 
1.7 mg/kg dose groups as 1.7 
mg/kg. Sort the bar by descending 
dose levels. Add foot note "Doses 
1.9 mg/kg and 1.7 mg/kg are 
combined and represented by 1.7 
mg/kg." 
SAC [A]
11.0030
All Treated
OEX12
Plot of Duration of Study Treatment by Response (Part 1)
Report for population subgroup: 
Part 1. Y axis: dose cohort. Use 
best confirmed response. Please 
add the footnote regarding 
treatment duration consistent with 
the one in OEX12.
SAC [A]
11.0031
All Treated
OEX12
Plot of Duration of Study Treatment by Response (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Y axis: dose cohort. Use 
best confirmed response. Please 
add the footnote regarding 
treatment duration consistent with 
the one in OEX12.
SAC [A]
11.0032
All Treated
OEX12
Plot of Duration of Study Treatment by Response (All Treated 
MM)
Report for population subgroup: All 
Treated MM. Y axis: dose cohort. 
Use best confirmed response. 
Please add the footnote regarding 
SAC [A]


CONFIDENTIAL
BMA117159
142
Study Population: Figures
No.
Population
IDSL /  
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
treatment duration consistent with 
the one in OEX12.
NOTES: 
A. Indicates which displays will be generated for the reporting effort for multiple myeloma
16.12.6.
Efficacy Tables
Efficacy: Tables
No.
Populati
on
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Response
2.0020
All 
Treated
RE1a
Summary of Investigator-Assessed Best Response (With 
Confirmation) (IMWG 2011) (Part 1)
Report for population subgroup: 
Part 1. Summarize by dose level; 
Do not include Total.
Best Response: Stringent Complete 
Response (sCR), Complete 
response (CR), Very Good Partial 
Response (VGPR), Partial 
Response (PR), Minimal Response 
(MR), Stable Disease (SD), 
Progressive Disease (PD), Not 
Evaluable (NE).
Overall Response Rate: 
(sCR+CR+VGPR+PR).
Clinical Benefit Rate: 
SAC [A]


CONFIDENTIAL
BMA117159
143
Efficacy: Tables
No.
Populati
on
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
(sCR+CR+VGPR+PR+MR).
Include: Overall Response Rate and 
Clinical Benefit Rate (No p-value) in 
one table.
2.0021
All 
Treated
RE1a
Summary of Investigator-Assessed Best Response (With 
Confirmation) (IMWG 2011) (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize for 3.4 MM.
Best Response: Stringent Complete 
Response (sCR), Complete 
response (CR), Very Good Partial 
Response (VGPR), Partial 
Response (PR), Minimal Response 
(MR), Stable Disease (SD), 
Progressive Disease (PD), Not 
Evaluable (NE).
Overall Response Rate: 
(sCR+CR+VGPR+PR).
Clinical Benefit Rate: 
(sCR+CR+VGPR+PR+MR).
Include: Overall Response Rate and 
Clinical Benefit Rate (No p-value) in 
one table.
SAC [A]
2.0180
All 
Treated
RE1a
Summary of Investigator-Assessed Best Response (With 
Confirmation) for Subjects with Prior Daratumumab Treatment 
and Refractory to Both IMiDs and Proteasomes Inhibitors 
(IMWG 2011) (Part 1)
Report for population subgroup: 
Part 1. Summarize by dose level; 
Do not include Total.
Best Response: Stringent Complete 
Response (sCR), Complete 
response (CR), Very Good Partial 
Response (VGPR), Partial 
SAC [A]


CONFIDENTIAL
BMA117159
144
Efficacy: Tables
No.
Populati
on
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Response (PR), Minimal Response 
(MR), Stable Disease (SD), 
Progressive Disease (PD), Not 
Evaluable (NE).
Overall Response Rate: 
(sCR+CR+VGPR+PR).
Clinical Benefit Rate: 
(sCR+CR+VGPR+PR+MR).
Include: Overall Response Rate and 
Clinical Benefit Rate (No p-value) in 
one table.
2.0181
All 
Treated
RE1a
Summary of Investigator-Assessed Best Response (With 
Confirmation) for Subjects with Prior Daratumumab Treatment 
and Refractory to Both IMiDs and Proteasomes Inhibitors 
(IMWG 2011) (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize for 3.4 MM.
Best Response: Stringent Complete 
Response (sCR), Complete 
response (CR), Very Good Partial 
Response (VGPR), Partial 
Response (PR), Minimal Response 
(MR), Stable Disease (SD), 
Progressive Disease (PD), Not 
Evaluable (NE).
Overall Response Rate: 
(sCR+CR+VGPR+PR).
Clinical Benefit Rate: 
(sCR+CR+VGPR+PR+MR).
Include: Overall Response Rate and 
Clinical Benefit Rate (No p-value) in 
one table.
SAC [A]


CONFIDENTIAL
BMA117159
145
Efficacy: Tables
No.
Populati
on
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
2.0110
All 
Treated
RE1a
Summary of Investigator-Assessed Best Response (With 
Confirmation) for Subjects without Prior Daratumumab treatment 
(IMWG 2011) (Part 1)
Report for population subgroup: 
Part 1. Summarize by dose level; 
Do not include Total.
Best Response: Stringent Complete 
Response (sCR), Complete 
response (CR), Very Good Partial 
Response (VGPR), Partial 
Response (PR), Minimal Response 
(MR), Stable Disease (SD), 
Progressive Disease (PD), Not 
Evaluable (NE).
Overall Response Rate: 
(sCR+CR+VGPR+PR).
Clinical Benefit Rate: 
(sCR+CR+VGPR+PR+MR).
Include: Overall Response Rate and 
Clinical Benefit Rate (No p-value) in 
one table.
SAC [A]
2.0111
All 
Treated
RE1a
Summary of Investigator-Assessed Best Response (With 
Confirmation) for Subjects without Prior Daratumumab treatment 
(IMWG 2011) (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize for 3.4 MM.
Best Response: Stringent Complete 
Response (sCR), Complete 
response (CR), Very Good Partial 
Response (VGPR), Partial 
Response (PR), Minimal Response 
(MR), Stable Disease (SD), 
Progressive Disease (PD), Not 
Evaluable (NE).
SAC [A]


CONFIDENTIAL
BMA117159
146
Efficacy: Tables
No.
Populati
on
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Overall Response Rate: 
(sCR+CR+VGPR+PR).
Clinical Benefit Rate: 
(sCR+CR+VGPR+PR+MR).
Include: Overall Response Rate and 
Clinical Benefit Rate (No p-value) in 
one table.
2.0040
All 
Treated
RE1a
Summary of Investigator-Assessed Best Response (With 
Confirmation) for Subjects refractory to Both IMiDs and 
Proteasome Inhibitors (IMWG 2011) (Part 1)
Report for population subgroup: 
Part 1. Summarize by dose level; 
Do not include Total.
Best Response: Stringent Complete 
Response (sCR), Complete 
response (CR), Very Good Partial 
Response (VGPR), Partial 
Response (PR), Minimal Response 
(MR), Stable Disease (SD), 
Progressive Disease (PD), Not 
Evaluable (NE).
Overall Response Rate: 
(sCR+CR+VGPR+PR).
Clinical Benefit Rate: 
(sCR+CR+VGPR+PR+MR).
Include: Overall Response Rate and 
Clinical Benefit Rate (No p-value) in 
one table.
SAC [A]
2.0041
All 
Treated
RE1a
Summary of Investigator-Assessed Best Response (With 
Confirmation) for Subjects refractory to Both IMiDs and 
Proteasome Inhibitors (IMWG 2011) (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize for 3.4 MM.
Best Response: Stringent Complete 
SAC [A]


CONFIDENTIAL
BMA117159
147
Efficacy: Tables
No.
Populati
on
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Response (sCR), Complete 
response (CR), Very Good Partial 
Response (VGPR), Partial 
Response (PR), Minimal Response 
(MR), Stable Disease (SD), 
Progressive Disease (PD), Not 
Evaluable (NE).
Overall Response Rate: 
(sCR+CR+VGPR+PR).
Clinical Benefit Rate: 
(sCR+CR+VGPR+PR+MR).
Include: Overall Response Rate and 
Clinical Benefit Rate (No p-value) in 
one table.
2.0060
All 
Evaluabl
e 
Subjects 
MM
RE1a
Summary of Investigator-Assessed Best Response (With 
Confirmation) (IMWG 2011) (All Evaluable Subjects MM)
Report for population subgroup: 
Part 2 MM. Summarize for 3.4 MM.
Best Response: Stringent Complete 
Response (sCR), Complete 
response (CR), Very Good Partial 
Response (VGPR), Partial 
Response (PR), Minimal Response 
(MR), Stable Disease (SD), 
Progressive Disease (PD), Not 
Evaluable (NE).
Overall Response Rate: 
(sCR+CR+VGPR+PR).
Clinical Benefit Rate: 
(sCR+CR+VGPR+PR+MR).
IA


CONFIDENTIAL
BMA117159
148
Efficacy: Tables
No.
Populati
on
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Include: Overall Response Rate and 
Clinical Benefit Rate (No p-value) in 
one table.
2.0342
All 
Treated
RE1a
Summary of Investigator-Assessed Best Response (With 
Confirmation) (RRMCL) (Part 2 NHL)
Report for population subgroup: 
Part 2 NHL. Summarize for 3.4 
NHL.
Best Response: Complete response 
(CR), Partial Response (PR). 
Minimal Response (MR), Stable 
Disease (SD), Progressive Disease 
(PD), Not Evaluable (NE). 
Overall Response Rate: (CR+PR).
SAC
Time-to Event Endpoint
2.0081
All 
Treated
TTE1a
Summary of Duration of Response (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize: only for 3.4 
MM. Do not include Hazard Ratio 
and Log-Rank P-Value.Only 
summarize for subjects with a 
confirmed PR or better.
SAC [A]
2.0201
All 
Treated
TTE1
Summary of Duration of Response for Subjects with Prior 
Daratumumab Treatment and Refractory to Both IMiDs and 
Proteasome Inhibitors (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize: only for 3.4 
MM. Do not include Hazard Ratio 
and Log-Rank P-Value.
SAC [A]
2.0161
All 
Treated
TTE1
Summary of Duration of Response for Subjects without Prior 
Daratumumab Treatment (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize: only for 3.4 
MM. Do not include Hazard Ratio 
and Log-Rank P-Value.
SAC [A]


CONFIDENTIAL
BMA117159
149
Efficacy: Tables
No.
Populati
on
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
2.0171
All 
Treated
TTE1
Summary of Duration of Response for Subjects Refractory to 
Both IMiDs and Proteasome Inhibitors (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize: only for 3.4 
MM. Do not include Hazard Ratio 
and Log-Rank P-Value.
SAC [A]
2.0071
All 
Treated
TTE1
Summary of Progression-Free Survival (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize: only for 3.4 
MM. Do not include Hazard Ratio 
and Log-Rank P-Value.
SAC [A]
2.0261
All 
Treated
TTE1
Summary of Progression-Free Survival for Subjects with Prior 
Daratumumab Treatment and Refractory to Both IMiDs and 
Proteasomes Inhibitors (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize: only for 3.4 
MM. Do not include Hazard Ratio 
and Log-Rank P-Value.
SAC [A]
2.0131
All 
Treated
TTE1
Summary of Progression-Free Survival for Subjects without Prior 
Daratumumab Treatment (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize: only for 3.4 
MM. Do not include Hazard Ratio 
and Log-Rank P-Value.
SAC [A]
2.0141
All 
Treated
TTE1
Summary of Progression-Free Survival for Subjects Refractory 
to Both IMiDs and Proteasome Inhibitors (Part 2 MM)
Summary of Progression-Free 
Survival for Subjects Refractory to 
Both IMiDs and Proteasome 
Inhibitors (Part 2 MM)
SAC [A]
2.0091
All 
Treated
TTE1a
Summary of Time to Response (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize: only for 3.4 
MM. Do not include Hazard Ratio 
and Log-Rank P-Value.
SAC [A]
2.0101
All 
Treated
TTE1a
Summary of Time to Progression (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize: only for 3.4 
MM. Do not include Hazard Ratio 
SAC [A]


CONFIDENTIAL
BMA117159
150
Efficacy: Tables
No.
Populati
on
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
and Log-Rank P-Value.
2.0311
All 
Treated
TTE1a
Summary of Time to Best Response (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize: only for 3.4 
MM. Do not include Hazard Ratio 
and Log-Rank P-Value.
SAC [A]
2.0321
All 
Treated
TTE6a
Summary of Kaplan-Meier Estimates of Overall Survival at 9 
Months (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize: only for 3.4 
MM. Produced if all the patients 
(who were alive at the time of study 
completion) can be re-consented.
SAC [A]
2.0331
All 
Treated
TTE6a
Summary of Kaplan-Meier Estimates of Overall Survival at One 
Year (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Summarize: only for 3.4 
MM. Produced if all the patients 
(who were alive at the time of study 
completion) can be re-consented.
SAC [A]
NOTES: 
A. Indicates which displays will be generated for the reporting effort for multiple myeloma


CONFIDENTIAL
BMA117159
151
16.12.7.
Efficacy Figures
Efficacy: Figures
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
M-Protein and FLC
12.0010
All Treated
RE8b
Percent Change at Maximum Reduction from Baseline in 
M-Protein (or FLC) Measurement (Part 1)
Report for population subgroup: 
Part 1. Include text for best 
confirmed response only. Remove 
subject ID. 
Include reference lines for 25%, 0, -
25%, -50%, -90%, -100%.. Indicate 
lab test types by different symbols. 
Indicate dose groups by different 
colours of the vertical bars.
SAC [A]
12.0011
All Treated
RE8b
Percent Change at Maximum Reduction from Baseline in 
M-Protein (or FLC) Measurement (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Include text for best 
confirmed response only. Remove 
subject ID. 
Include reference lines for 25%, 0, -
25%, -50%, -90%, -100%. Indicate 
lab test types by different shades.
SAC [A]
12.0020
All Treated
EFF_F1
Correlation of Free Soluble BCMA at Pre-Dose (Cycle 1) 
and Maximum Percentage Change from Baseline in Serum 
M-Protein, Urine M-Protein or Serum FLC (Part 1)
Report for population subgroup: 
Part 1. Use best confirmed 
response. Colored by different dose 
groups. Use different symbols to 
indicate Serum M-protein, Urine M-
protein, and Serum FLC. Do not 
include R square and fitted line.
SAC [A]


CONFIDENTIAL
BMA117159
152
Efficacy: Figures
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
12.0021
All Treated
EFF_F1
Correlation of Free Soluble BCMA at Pre-Dose (Cycle 1) 
and Maximum Percentage Change from Baseline in Serum 
M-Protein, Urine M-Protein or Serum FLC (Part 2 MM)
Report for population subgroup: 
Part 2 MM. Use best confirmed 
response. Do not include R square 
and fitted line.
SAC [A]
Time-to-Event Endpoint
12.0041
All Treated
TTE10
Graph of Kaplan Meier Progression-Free Survival Curves 
(Part 2 MM)
Report for population subgroup: 
Part 2 MM.
SAC [A]
12.0161
All Treated
TTE10
Graph of Kaplan Meier Progression-Free Survival Curves 
for Subjects with Prior Daratumumab Treatment and 
Refractory to Both IMiDs and Proteasomes Inhibitors (Part 
2 MM)
Report for population subgroup: 
Part 2 MM.
SAC [A]
12.0081
All Treated
TTE10
Graph of Kaplan Meier Progression-Free Survival Curves 
for Subjects Refractory to Both IMiDs and Proteasome 
Inhibitors (Part 2 MM)
Report for population subgroup: 
Part 2 MM.
SAC [A]
12.0071
All Treated
TTE10
Graph of Kaplan Meier Progression-Free Survival Curves 
for Subjects without Prior Daratumumab Treatment (Part 2 
MM)
Report for population subgroup: 
Part 2 MM.
SAC [A]
12.0051
All Treated
TTE10
Graph of Kaplan Meier Curves of Duration of Response 
(Part 2 MM)
Report for population subgroup: 
Part 2 MM.and only for subjects 
with a confirmed PR or better.
SAC [A]
12.0171
All Treated
TTE10
Graph of Kaplan Meier Curves of Duration of Response for 
Subjects with Prior Daratumumab Treatment and 
Refractory to Both IMiDs and Proteasomes Inhibitors (Part 
2 MM)
Report for population subgroup: 
Part 2 MM.
SAC [A]


CONFIDENTIAL
BMA117159
153
Efficacy: Figures
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
12.0101
All Treated
TTE10
Graph of Kaplan Meier Curves of Duration of Response for 
Subjects without Prior Daratumumab Treatment (Part 2 
MM)
Report for population subgroup: 
Part 2 MM.
SAC [A]
12.0111
All Treated
TTE10
Graph of Kaplan Meier Curves of Duration of Response for 
Subjects Refractory to Both IMiDs and Proteasome 
Inhibitors (Part 2 MM)
Report for population subgroup: 
Part 2 MM.
SAC [A]
Forest Plot
12.0120
All Treated
EFF_F2
Forest Plot - Overall Response Rate (ORR) (Part 2 MM)
SAC [A]
Profile Plot of Responders
12.0150
All Treated
EFF_F3
Profile Plot of Responders (Part 2 MM)
Report for population subgroup: 
Part 2 MM.
SAC [A]
NOTES: 
A. Indicates which displays will be generated for the reporting effort for multiple myeloma


CONFIDENTIAL
BMA117159
154
16.12.8.
Safety Tables
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Adverse Events (AEs)
3.0030
All Treated
OAE01
Summary of All Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0031
All Treated
OAE01
Summary of All Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0032
All Treated
OAE01
Summary of All Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0033
All Treated
OAE01
Summary of All Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0040
All Treated
AE3
Summary of All Adverse Events by Preferred Term (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0041
All Treated
AE3
Summary of All Adverse Events by Preferred Term (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0042
All Treated
AE3
Summary of All Adverse Events by Preferred Term (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0043
All Treated
AE3
Summary of All Adverse Events by Preferred Term (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0910
All Treated
OAE07
Summary of All Adverse Events by Preferred Term and 
Maximum Grade (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0911
All Treated
OAE07
Summary of All Adverse Events by Preferred Term and 
Maximum Grade (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0912
All Treated
OAE07
Summary of All Adverse Events by Preferred Term and 
Maximum Grade (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]


CONFIDENTIAL
BMA117159
155
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0913
All Treated
OAE07
Summary of All Adverse Events by Preferred Term and 
Maximum Grade (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0720
All Treated
OAE1
Summary of All Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade for Subjects with Prior 
Daratumumab Treatment and Refractory to Both IMiDs and 
Proteasomes Inhibitors (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0721
All Treated
OAE1
Summary of All Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade for Subjects with Prior 
Daratumumab Treatment and Refractory to Both IMiDs and 
Proteasomes Inhibitors (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0722
All Treated
OAE1
Summary of All Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade for Subjects with Prior 
Daratumumab Treatment and Refractory to Both IMiDs and 
Proteasomes Inhibitors (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0730
All Treated
OAE1
Summary of All Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade for Subjects without Prior 
Daratumumab Treatment (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0731
All Treated
OAE1
Summary of All Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade for Subjects without Prior 
Daratumumab Treatment (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0732
All Treated
OAE1
Summary of All Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade for Subjects without Prior 
Daratumumab Treatment (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0740
All Treated
OAE1
Summary of All Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade for Subjects Refractory to 
Both IMiDs and Proteasomes Inhibitors (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]


CONFIDENTIAL
BMA117159
156
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0741
All Treated
OAE1
Summary of All Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade for Subjects Refractory to 
Both IMiDs and Proteasomes Inhibitors (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0742
All Treated
OAE1
Summary of All Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade for Subjects Refractory to 
Both IMiDs and Proteasomes Inhibitors (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0750
All Treated
AE3
Summary of All Adverse Events by Preferred Term for Subjects 
with Prior Daratumumab Treatment and Refractory to Both 
IMiDs and Proteasomes Inhibitors (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0751
All Treated
AE3
Summary of All Adverse Events by Preferred Term for Subjects 
with Prior Daratumumab Treatment and Refractory to Both 
IMiDs and Proteasomes Inhibitors (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0752
All Treated
AE3
Summary of All Adverse Events by Preferred Term for Subjects 
with Prior Daratumumab Treatment and Refractory to Both 
IMiDs and Proteasomes Inhibitors (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0760
All Treated
AE3
Summary of All Adverse Events by Preferred Term for Subjects 
without Prior Daratumumab Treatment (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0761
All Treated
AE3
Summary of All Adverse Events by Preferred Term for Subjects 
without Prior Daratumumab Treatment (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0762
All Treated
AE3
Summary of All Adverse Events by Preferred Term for Subjects 
without Prior Daratumumab Treatment (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0770
All Treated
AE3
Summary of All Adverse Events by Preferred Term for Subjects 
Refractory to Both IMiDs and Proteasomes Inhibitors (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]


CONFIDENTIAL
BMA117159
157
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0771
All Treated
AE3
Summary of All Adverse Events by Preferred Term for Subjects 
Refractory to Both IMiDs and Proteasomes Inhibitors (Part 2 
MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0772
All Treated
AE3
Summary of All Adverse Events by Preferred Term for Subjects 
Refractory to Both IMiDs and Proteasomes Inhibitors (All 
Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0780
All Treated
AE3
Summary of Common (>=5%) Adverse Events by Overall 
Frequency (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0781
All Treated
AE3
Summary of Common (>=5%) Adverse Events by Overall 
Frequency (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0782
All Treated
AE3
Summary of Common (>=5%) Adverse Events by Overall 
Frequency (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0783
All Treated
AE3
Summary of Common (>=5%) Adverse Events by Overall 
Frequency (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0790
All Treated
AE3
Summary of Common (>=5%) Grade 2-4 Adverse Events by 
Overall Frequency (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0791
All Treated
AE3
Summary of Common (>=5%) Grade 2-4 Adverse Events by 
Overall Frequency (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0792
All Treated
AE3
Summary of Common (>=5%) Grade 2-4 Adverse Events by 
Overall Frequency (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0793
All Treated
AE3
Summary of Common (>=5%) Grade 2-4 Adverse Events by 
Overall Frequency (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0060
All Treated
OAE01
Summary of All Drug-Related Adverse Events by System Organ 
Class and Preferred Term and Maximum Grade (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]


CONFIDENTIAL
BMA117159
158
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0061
All Treated
OAE01
Summary of All Drug-Related Adverse Events by System Organ 
Class and Preferred Term and Maximum Grade (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0062
All Treated
OAE01
Summary of All Drug-Related Adverse Events by System Organ 
Class and Preferred Term and Maximum Grade (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0063
All Treated
OAE01
Summary of All Drug-Related Adverse Events by System Organ 
Class and Preferred Term and Maximum Grade (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0690
All Treated
AE15
Summary of Common (>=5%) Non-serious Adverse Events by 
System Organ Class and Preferred Term (Number of 
Participants and Occurrences) (Part 1)
Report for: Part 1, (Summarize by 
ascending dose level, Total). 
SAC [A]
3.0691
All Treated
AE15
Summary of Common (>=5%) Non-serious Adverse Events by 
System Organ Class and Preferred Term (Number of 
Participants and Occurrences) (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). 
SAC [A]
3.0692
All Treated
AE15
Summary of Common (>=5%) Non-serious Adverse Events by 
System Organ Class and Preferred Term (Number of 
Participants and Occurrences) (All Treated MM)
Report for: All Treated MM, 
(Summarize for Total). Include 
baseline values.
SAC [A]
3.0693
All Treated
AE15
Summary of Common (>=5%) Non-serious Adverse Events by 
System Organ Class and Preferred Term (Number of 
Participants and Occurrences) (Part 2 NHL)
Report for: Part 2 NHL, (Summarize 
for Total). Include baseline values.
SAC
3.0710
All Treated
AE3
Summary of Common (>=5%) Drug-Related Grade 2-4 Adverse 
Events by Overall Frequency (Part 1)
Report for: Part 1, (Summarize by 
ascending dose level, Total). 
Include baseline values.
SAC [A]
3.0711
All Treated
AE3
Summary of Common (>=5%) Drug-Related Grade 2-4 Adverse 
Events by Overall Frequency (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Include baseline 
values.
SAC [A]


CONFIDENTIAL
BMA117159
159
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0712
All Treated
AE3
Summary of Common (>=5%) Drug-Related Grade 2-4 Adverse 
Events by Overall Frequency (All Treated MM)
Report for: All Treated MM, 
(Summarize for Total). Include 
baseline values.
SAC [A]
3.0713
All Treated
AE3
Summary of Common (>=5%) Drug-Related Grade 2-4 Adverse 
Events by Overall Frequency (Part 2 NHL)
Report for: Part 2 NHL, (Summarize 
for Total). Include baseline values.
SAC
3.0010
All Treated
AE13
Adverse Event Overview (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0011
All Treated
AE13
Adverse Event Overview (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0012
All Treated
AE13
Adverse Event Overview (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0013
All Treated
AE13
Adverse Event Overview (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0100
All Treated
AE1
Summary of Adverse Events of Maximum Grade 3 or Higher by 
System Organ Class and Preferred Term (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0101
All Treated
AE1
Summary of Adverse Events of Maximum Grade 3 or Higher by 
System Organ Class and Preferred Term (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0102
All Treated
AE1
Summary of Adverse Events of Maximum Grade 3 or Higher by 
System Organ Class and Preferred Term (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0103
All Treated
AE1
Summary of Adverse Events of Maximum Grade 3 or Higher by 
System Organ Class and Preferred Term (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0170
DLT 
Evaluable
DL1
Summary of Dose-Limiting Toxicities during the Determinative 
Period (Part 1) (Day 1-21) 
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
Section 3.3.3 of the protocol: An 
event will be
SAC [A]


CONFIDENTIAL
BMA117159
160
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
considered a DLT if its relationship 
to the investigational agent cannot 
be ruled out occurs within the DLT 
reporting period (first 21 days of 
treatment for schedule 1, and
first 28 days for schedule 2)
Serious and Other Significant Adverse Events
3.0700
All Treated
AE16
Summary of Serious Adverse Events by System Organ Class 
and Preferred Term (Number of Participants and Occurrences) 
(Part 1)
Report for: Part 1, (Summarize by 
ascending dose level, Total). 
Include baseline values.
SAC [A]
3.0701
All Treated
AE16
Summary of Serious Adverse Events by System Organ Class 
and Preferred Term (Number of Participants and Occurrences) 
(Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Include baseline 
values.
SAC [A]
3.0702
All Treated
AE16
Summary of Serious Adverse Events by System Organ Class 
and Preferred Term (Number of Participants and Occurrences) 
(All Treated MM)
Report for: All Treated MM, 
(Summarize for Total). Include 
baseline values.
SAC [A]
3.0703
All Treated
AE16
Summary of Serious Adverse Events by System Organ Class 
and Preferred Term (Number of Participants and Occurrences) 
(Part 2 NHL)
Report for: Part 2 NHL, (Summarize 
for Total). Include baseline values.
SAC
3.0080
All Treated
AE1
Summary of Drug-Related Serious Adverse Events by System 
Organ Class and Preferred Term (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0081
All Treated
AE1
Summary of Drug-Related Serious Adverse Events by System 
Organ Class and Preferred Term (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0082
All Treated
AE1
Summary of Drug-Related Serious Adverse Events by System 
Organ Class and Preferred Term (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]


CONFIDENTIAL
BMA117159
161
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0083
All Treated
AE1
Summary of Drug-Related Serious Adverse Events by System 
Organ Class and Preferred Term (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0800
All Treated
AE1
Summary of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment or Withdrawal from Study by 
System Organ Class and Preferred Term (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0801
All Treated
AE1
Summary of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment or Withdrawal from Study by 
System Organ Class and Preferred Term (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0802
All Treated
AE1
Summary of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment or Withdrawal from Study by 
System Organ Class and Preferred Term (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0803
All Treated
AE1
Summary of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment or Withdrawal from Study by 
System Organ Class and Preferred Term (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0120
All Treated
AE1
Summary of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment by System Organ Class and 
Preferred Term (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0121
All Treated
AE1
Summary of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment by System Organ Class and 
Preferred Term (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0122
All Treated
AE1
Summary of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment by System Organ Class and 
Preferred Term (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0123
All Treated
AE1
Summary of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment by System Organ Class and 
Preferred Term (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC


CONFIDENTIAL
BMA117159
162
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0130
All Treated
AE1
Summary of Adverse Events Leading to Dose Reduction by 
System Organ Class and Preferred Term (Part 1)
Report for: Part 1, (Summarize: by
ascending dose level, Total).
SAC [A]
3.0131
All Treated
AE1
Summary of Adverse Events Leading to Dose Reduction by 
System Organ Class and Preferred Term (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0132
All Treated
AE1
Summary of Adverse Events Leading to Dose Reduction by 
System Organ Class and Preferred Term (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0133
All Treated
AE1
Summary of Adverse Events Leading to Dose Reduction by 
System Organ Class and Preferred Term (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0140
All Treated
AE1
Summary of Adverse Events Leading to Dose Interruptions or 
Delays by System Organ Class and Preferred Term (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0141
All Treated
AE1
Summary of Adverse Events Leading to Dose Interruptions or 
Delays by System Organ Class and Preferred Term (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0142
All Treated
AE1
Summary of Adverse Events Leading to Dose Interruptions or 
Delays by System Organ Class and Preferred Term (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0143
All Treated
AE1
Summary of Adverse Events Leading to Dose Interruptions or 
Delays by System Organ Class and Preferred Term (Part 2 
NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0630
All Treated
AE1
Summary of Adverse Events Leading to Dose Reductions, 
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by System Organ Class (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0631
All Treated
AE1
Summary of Adverse Events Leading to Dose Reductions, 
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by System Organ Class (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0632
All Treated
AE1
Summary of Adverse Events Leading to Dose Reductions, 
Report for: All Treated MM, 
SAC [A]


CONFIDENTIAL
BMA117159
163
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by System Organ Class (All Treated MM)
(Summarize: Total).
3.0633
All Treated
AE1
Summary of Adverse Events Leading to Dose Reductions, 
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by System Organ Class (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0640
All Treated
AE1
Summary of Adverse Events Leading to Dose Reductions, 
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by HLGT (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0641
All Treated
AE1
Summary of Adverse Events Leading to Dose Reductions, 
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by HLGT (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0642
All Treated
AE1
Summary of Adverse Events Leading to Dose Reductions, 
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by HLGT (All Treated MM)
Report for: All Treated MM,
(Summarize: Total).
SAC [A]
3.0643
All Treated
AE1
Summary of Adverse Events Leading to Dose Reductions, 
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by HLGT (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0650
All Treated
AE1
Summary of Adverse Events Leading to Dose Reductions, 
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by HLT (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0651
All Treated
AE1
Summary of Adverse Events Leading to Dose Reductions, 
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by HLT (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0652
All Treated
AE1
Summary of Adverse Events Leading to Dose Reductions, 
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by HLT (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]


CONFIDENTIAL
BMA117159
164
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0653
All Treated
AE1
Summary of Adverse Events Leading to Dose Reductions, 
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by HLT (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0660
All Treated
AE3
Summary of Adverse Events Leading to Dose Reductions, 
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by Preferred Term (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0661
All Treated
AE3
Summary of Adverse Events Leading to Dose Reductions, 
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by Preferred Term (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0662
All Treated
AE3
Summary of Adverse Events Leading to Dose Reductions, 
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by Preferred Term (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0663
All Treated
AE3
Summary of Adverse Events Leading to Dose Reductions, 
Interruptions or Delays, Permanent Discontinuation of Study 
Treatment by Preferred Term (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
Adverse Events of Interest
3.0430
All Treated
OAE07
Summary of Corneal Events by Preferred Term and Maximum 
Grade (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0431
All Treated
OAE07
Summary of Corneal Events by Preferred Term and Maximum 
Grade (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM) 
SAC [A]
3.0432
All Treated
OAE07
Summary of Corneal Events by Preferred Term and Maximum 
Grade (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total
SAC [A]
3.0433
All Treated
OAE07
Summary of Corneal Events by Preferred Term and Maximum 
Grade (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) 
SAC
3.0520
All Treated
ESI1
Summary of Characteristics of Corneal Events (Part 1)
Report for: Part 1, (Summarize: by 
SAC [A]


CONFIDENTIAL
BMA117159
165
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
ascending dose level, Total).
Summary based on both all 
subjects and subjects with events.
3.0521
All Treated
ESI1
Summary of Characteristics of Corneal Events (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Summary based 
on both all subjects and subjects 
with events.
SAC [A]
3.0522
All Treated
ESI1
Summary of Characteristics of Corneal Events (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Summary 
based on both all subjects and 
subjects with events.
SAC [A]
3.0523
All Treated
ESI1
Summary of Characteristics of Corneal Events (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
Summary based on both all 
subjects and subjects with events.
SAC
3.0180
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Corneal Events (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). Time 
of onset: 1-21, 22-42, 43-63, >63. 
Duration till resolution: 1-21, 22-42, 
>42.
SAC [A]
3.0181
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Corneal Events (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM) Time of onset: 1-
21, 22-42, 43-63, >63. Duration till 
resolution: 1-21, 22-42, >42.
SAC [A]
3.0182
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Corneal Events (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Time of onset: 
1-21, 22-42, 43-63, >63. Duration till 
SAC [A]


CONFIDENTIAL
BMA117159
166
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
resolution: 1-21, 22-42, >42.
3.0183
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Corneal Events (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) Time 
of onset: 1-21, 22-42, 43-63, >63. 
Duration till resolution: 1-21, 22-42, 
>42.
SAC
3.0150
All Treated
AE3
Summary of Corneal Events Leading to Dose Reduction by 
Preferred Term (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0151
All Treated
AE3
Summary of Corneal Events Leading to Dose Reduction by 
Preferred Term (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0152
All Treated
AE3
Summary of Corneal Events Leading to Dose Reduction by 
Preferred Term (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0153
All Treated
AE3
Summary of Corneal Events Leading to Dose Reduction by 
Preferred Term (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0160
All Treated
AE3
Summary of Corneal Events Leading to Dose Interruptions or 
Delays by Preferred Term (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0161
All Treated
AE3
Summary of Corneal Events Leading to Dose Interruptions or 
Delays by Preferred Term (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0162
All Treated
AE3
Summary of Corneal Events Leading to Dose Interruptions or 
Delays by Preferred Term (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0163
All Treated
AE3
Summary of Corneal Events Leading to Dose Interruptions or 
Delays by Preferred Term (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0560
All Treated
OAE07
Summary of Thrombocytopenia by Preferred Term and 
Maximum Grade (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0561
All Treated
OAE07
Summary of Thrombocytopenia by Preferred Term and 
Report for: Part 2 MM, (Summarize: 
SAC [A]


CONFIDENTIAL
BMA117159
167
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Maximum Grade (Part 2 MM)
only for 3.4 MM)
3.0562
All Treated
OAE07
Summary of Thrombocytopenia by Preferred Term and 
Maximum Grade (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0563
All Treated
OAE07
Summary of Thrombocytopenia by Preferred Term and 
Maximum Grade (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0530
All Treated
ESI1
Summary of Characteristics of Thrombocytopenia (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
Summary based on both all 
subjects and subjects with events.
SAC [A]
3.0531
All Treated
ESI1
Summary of Characteristics of Thrombocytopenia (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Summary based 
on both all subjects and subjects 
with events.
SAC [A]
3.0532
All Treated
ESI1
Summary of Characteristics of Thrombocytopenia (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total). Summary 
based on both all subjects and 
subjects with events.
SAC [A]
3.0533
All Treated
ESI1
Summary of Characteristics of Thrombocytopenia (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL). 
Summary based on both all 
subjects and subjects with events.
SAC
3.0190
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Thrombocytopenia (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). Time 
of onset: 1-21, 22-42, 43-63, >63. 
Duration till resolution: 1-21, 22-42, 
>42. Thrombocytopenia should 
SAC [A]


CONFIDENTIAL
BMA117159
168
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
include both 'thrombocytopenia' and 
'platelet count decreased'
3.0191
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Thrombocytopenia (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM) Time of onset: 1-
21, 22-42, 43-63, >63. Duration till 
resolution: 1-21, 22-42, >42. 
Thrombocytopenia should include 
both 'thrombocytopenia' and 
'platelet count decreased'
SAC [A]
3.0192
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Thrombocytopenia (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Time of onset: 
1-21, 22-42, 43-63, >63. Duration till 
resolution: 1-21, 22-42, >42. 
Thrombocytopenia should include 
both 'thrombocytopenia' and 
'platelet count decreased'
SAC [A]
3.0193
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Thrombocytopenia (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) Time 
of onset: 1-21, 22-42, 43-63, >63. 
Duration till resolution: 1-21, 22-42, 
>42. Thrombocytopenia should 
include both 'thrombocytopenia' and 
'platelet count decreased'
SAC
3.0580
All Treated
OAE07
Summary of Neutropenia by Preferred Term and Maximum 
Grade (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0581
All Treated
OAE07
Summary of Neutropenia by Preferred Term and Maximum 
Grade (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]


CONFIDENTIAL
BMA117159
169
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0582
All Treated
OAE07
Summary of Neutropenia by Preferred Term and Maximum 
Grade (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0583
All Treated
OAE07
Summary of Neutropenia by Preferred Term and Maximum 
Grade (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0590
All Treated
ESI1
Summary of Characteristics of Neutropenia (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
Summary based on both all 
subjects and subjects with events.
SAC [A]
3.0591
All Treated
ESI1
Summary of Characteristics of Neutropenia (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Summary based 
on both all subjects and subjects 
with events.
SAC [A]
3.0592
All Treated
ESI1
Summary of Characteristics of Neutropenia (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Summary 
based on both all subjects and 
subjects with events.
SAC [A]
3.0593
All Treated
ESI1
Summary of Characteristics of Neutropenia (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
Summary based on both all 
subjects and subjects with events.
SAC
3.0860
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Neutropenia (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). Time 
of onset: 1-21, 22-42, 43-63, >63. 
Duration till resolution: 1-21, 22-42, 
>42.
SAC [A]
3.0861
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Report for: Part 2 MM, (Summarize: 
SAC [A]


CONFIDENTIAL
BMA117159
170
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Neutropenia (Part 2 MM)
only for 3.4 MM) Time of onset: 1-
21, 22-42, 43-63, >63. Duration till 
resolution: 1-21, 22-42, >42.
3.0862
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Neutropenia (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Time of onset: 
1-21, 22-42, 43-63, >63. Duration till 
resolution: 1-21, 22-42, >42.
SAC [A]
3.0863
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Neutropenia (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) Time 
of onset: 1-21, 22-42, 43-63, >63. 
Duration till resolution: 1-21, 22-42, 
>42.
SAC
3.0550
All Treated
OAE07
Summary of Hematologic Toxicity by Preferred Term and 
Maximum Grade (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0551
All Treated
OAE07
Summary of Hematologic Toxicity by Preferred Term and 
Maximum Grade (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0552
All Treated
OAE07
Summary of Hematologic Toxicity by Preferred Term and 
Maximum Grade (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0553
All Treated
OAE07
Summary of Hematologic Toxicity by Preferred Term and 
Maximum Grade (Part 2 NHL)
Report for: All Treated MM, 
(Summarize: Total).
SAC
3.0540
All Treated
ESI1
Summary of Characteristics of Hematologic Toxicity (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
Summary based on both all 
subjects and subjects with events.
SAC [A]
3.0541
All Treated
ESI1
Summary of Characteristics of Hematologic Toxicity (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Summary based 
SAC [A]


CONFIDENTIAL
BMA117159
171
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
on both all subjects and subjects 
with events.
3.0542
All Treated
ESI1
Summary of Characteristics of Hematologic Toxicity (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total). Summary 
based on both all subjects and 
subjects with events.
SAC [A]
3.0543
All Treated
ESI1
Summary of Characteristics of Hematologic Toxicity (Part 2 
NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL).
Summary based on both all 
subjects and subjects with events.
SAC
3.0870
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Hematologic Toxicity (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). Time 
of onset: 1-21, 22-42, 43-63, >63. 
Duration till resolution: 1-21, 22-42, 
>42.
SAC [A]
3.0871
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Hematologic Toxicity (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM) Time of onset: 1-
21, 22-42, 43-63, >63. Duration till 
resolution: 1-21, 22-42, >42.
SAC [A]
3.0872
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Hematologic Toxicity (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Time of onset: 
1-21, 22-42, 43-63, >63. Duration till 
resolution: 1-21, 22-42, >42.
SAC [A]
3.0873
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Hematologic Toxicity (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) Time 
of onset: 1-21, 22-42, 43-63, >63. 
Duration till resolution: 1-21, 22-42, 
SAC


CONFIDENTIAL
BMA117159
172
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
>42.
3.0110
All Treated
OAE07
Summary of Infusion-Related Reactions by Preferred Term and 
Maximum Grade (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0111
All Treated
OAE07
Summary of Infusion-Related Reactions by Preferred Term and 
Maximum Grade (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0112
All Treated
OAE07
Summary of Infusion-Related Reactions by Preferred Term and 
Maximum Grade (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0113
All Treated
OAE07
Summary of Infusion-Related Reactions by Preferred Term and 
Maximum Grade (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0600
All Treated
ESI1
Summary of Characteristics of Infusion-Related Reactions (Part 
1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
Summary based on both all 
subjects and subjects with events.
SAC [A]
3.0601
All Treated
ESI1
Summary of Characteristics of Infusion-Related Reactions (Part 
2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Summary based 
on both all subjects and subjects 
with events.
SAC [A]
3.0602
All Treated
ESI1
Summary of Characteristics of Infusion-Related Reactions (All 
Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Summary 
based on both all subjects and 
subjects with events.
SAC [A]
3.0603
All Treated
ESI1
Summary of Characteristics of Infusion-Related Reactions (Part 
2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL). 
Summary based on both all 
subjects and subjects with events.
SAC
3.0880
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Report for: Part 1, (Summarize: by 
SAC [A]


CONFIDENTIAL
BMA117159
173
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Infusion-Related Reactions (Part 1)
ascending dose level, Total). Time 
of onset: 1-21, 22-42, 43-63, >63. 
Duration till resolution: 1-21, 22-42, 
>42.
3.0881
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Infusion-Related Reactions (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM) Time of onset: 1-
21, 22-42, 43-63, >63. Duration till 
resolution: 1-21, 22-42, >42.
SAC [A]
3.0882
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Infusion-Related Reactions (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Time of onset: 
1-21, 22-42, 43-63, >63. Duration till 
resolution: 1-21, 22-42, >42.
SAC [A]
3.0883
All Treated
ESI2b
Summary of Onset and Duration of the First Occurrence of 
Infusion-Related Reactions (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) Time 
of onset: 1-21, 22-42, 43-63, >63. 
Duration till resolution: 1-21, 22-42, 
>42.
SAC
Laboratory: Chemistry 
3.0270
All Treated
LB1
Summary of Chemistry Changes from Baseline (Part 1)
Report for: Part 1, (Summarize by 
ascending dose level, Total). 
Include baseline values.
SAC [A]
3.0271
All Treated
LB1
Summary of Chemistry Changes from Baseline (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Include baseline 
values.
SAC [A]
3.0272
All Treated
LB1
Summary of Chemistry Changes from Baseline (All Treated MM)
Report for: All Treated MM, 
(Summarize for Total). Include 
SAC [A]


CONFIDENTIAL
BMA117159
174
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
baseline values.
3.0273
All Treated
LB1
Summary of Chemistry Changes from Baseline (Part 2 NHL)
Report for: Part 2 NHL, (Summarize 
for Total). Include baseline values.
SAC
3.0280
All Treated
OLB11B
Summary of Chemistry Changes from Baseline with Respect to 
the Normal Range (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
Include only 'worst-case post-
baseline'
SAC [A]
3.0281
All Treated
OLB11B
Summary of Chemistry Changes from Baseline with Respect to 
the Normal Range (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM) Include only 'worst-
case post-baseline'
SAC [A]
3.0282
All Treated
OLB11B
Summary of Chemistry Changes from Baseline with Respect to 
the Normal Range (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Include only
'worst-case post-baseline'
SAC [A]
3.0283
All Treated
OLB11B
Summary of Chemistry Changes from Baseline with Respect to 
the Normal Range (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) 
Include only 'worst-case post-
baseline'
SAC
3.0290
All Treated
OLB9B
Summary of Chemistry Grade Changes from Baseline Grade 
(Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
Produce only for lab tests that are 
graded. For laboratory tests that are 
graded for both low and high 
values, summaries will be done 
separately and labeled by direction. 
Include only 'worst-case post-
baseline'
SAC [A]


CONFIDENTIAL
BMA117159
175
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0291
All Treated
OLB9B
Summary of Chemistry Grade Changes from Baseline Grade 
(Part 2 MM)
Report for: Part 2 MM, (Summarize: 
by starting dose level and tumor 
type, Total). Produce only for lab 
tests that are graded. For laboratory 
tests that are graded for both low 
and high values, summaries will be 
done separately and labeled by 
direction. Include only 'worst-case 
post-baseline'
SAC [A]
3.0292
All Treated
OLB9B
Summary of Chemistry Grade Changes from Baseline Grade 
(All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Produce only 
for lab tests that are graded. For 
laboratory tests that are graded for 
both low and high values, 
summaries will be done separately 
and labeled by direction. Include 
only 'worst-case post-baseline'
SAC [A]
3.0293
All Treated
OLB9B
Summary of Chemistry Grade Changes from Baseline Grade 
(Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: Total). Produce only 
for lab tests that are graded. For 
laboratory tests that are graded for 
both low and high values, 
summaries will be done separately 
and labeled by direction. Include 
only 'worst-case post-baseline'
SAC
3.0450
All Treated
OLB11B
Summary of LDH Laboratory Results (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
Include only 'worst-case post-
SAC [A]


CONFIDENTIAL
BMA117159
176
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
baseline'. The categories for 
summary are: <1xULN, >=1xULN 
and < 2xULN, >=2xULN and < 
5xULN, >=5xULN and < 10xULN, 
>=10xULN.
3.0451
All Treated
OLB11B
Summary of LDH Laboratory Results (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM) Include only 'worst-
case post-baseline. The categories 
for summary are: <1xULN, 
>=1xULN and < 2xULN, >=2xULN 
and < 5xULN, >=5xULN and < 
10xULN, >=10xULN.
SAC [A]
3.0452
All Treated
OLB11B
Summary of LDH Laboratory Results (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Include only 
'worst-case post-baseline. The 
categories for summary are: 
<1xULN, >=1xULN and < 2xULN, 
>=2xULN and < 5xULN, >=5xULN 
and < 10xULN, >=10xULN.
SAC [A]
3.0453
All Treated
OLB11B
Summary of LDH Laboratory Results (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) 
Include only 'worst-case post-
baseline. The categories for 
summary are: <1xULN, >=1xULN 
and < 2xULN, >=2xULN and < 
5xULN, >=5xULN and < 10xULN, 
>=10xULN.
SAC


CONFIDENTIAL
BMA117159
177
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0470
All Treated
OLB11B
Summary of Creatine Kinase Laboratory Results (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
Include only 'worst-case post-
baseline'. The categories for 
summary are: <1xULN, >=1xULN 
and < 2xULN, >=2xULN and < 
5xULN, >=5xULN and < 10xULN, 
>=10xULN.
SAC [A]
3.0471
All Treated
OLB11B
Summary of Creatine Kinase Laboratory Results (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM) Include only 'worst-
case post-baseline. The categories 
for summary are: <1xULN, 
>=1xULN and < 2xULN, >=2xULN 
and < 5xULN, >=5xULN and < 
10xULN, >=10xULN.
SAC [A]
3.0472
All Treated
OLB11B
Summary of Creatine Kinase Laboratory Results (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total). Include only 
'worst-case post-baseline. The 
categories for summary are: 
<1xULN, >=1xULN and < 2xULN, 
>=2xULN and < 5xULN, >=5xULN 
and < 10xULN, >=10xULN.
SAC [A]
3.0473
All Treated
OLB11B
Summary of Creatine Kinase Laboratory Results (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) 
Include only 'worst-case post-
baseline. The categories for 
summary are: <1xULN, >=1xULN 
and < 2xULN, >=2xULN and < 
SAC


CONFIDENTIAL
BMA117159
178
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
5xULN, >=5xULN and < 10xULN, 
>=10xULN.
Laboratory: Hematology
3.0300
All Treated
LB1
Summary of Hematology Changes from Baseline (Part 1)
Report for: Part 1, (Summarize by 
ascending dose level, Total). 
Include baseline values.
SAC [A]
3.0301
All Treated
LB1
Summary of Hematology Changes from Baseline (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Include baseline 
values.
SAC [A]
3.0302
All Treated
LB1
Summary of Hematology Changes from Baseline (All Treated 
MM)
Report for: All Treated MM, 
(Summarize for Total). Include 
baseline values.
SAC [A]
3.0303
All Treated
LB1
Summary of Hematology Changes from Baseline (Part 2 NHL)
Report for: Part 2 NHL, (Summarize 
for Total). Include baseline values.
SAC
3.0310
All Treated
OLB11B
Summary of Hematology Changes from Baseline with Respect 
to the Normal Range (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
Include only 'worst-case post-
baseline'
SAC [A]
3.0311
All Treated
OLB11B
Summary of Hematology Changes from Baseline with Respect 
to the Normal Range (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM) Include only 'worst-
case post-baseline'
SAC [A]
3.0312
All Treated
OLB11B
Summary of Hematology Changes from Baseline with Respect 
to the Normal Range (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Include only 
'worst-case post-baseline'
SAC [A]
3.0313
All Treated
OLB11B
Summary of Hematology Changes from Baseline with Respect 
to the Normal Range (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) 
SAC


CONFIDENTIAL
BMA117159
179
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Include only 'worst-case post-
baseline'
3.0320
All Treated
OLB9B
Summary of Hematology Grade Changes from Baseline Grade 
(Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
Produce only for lab tests that are 
graded. For laboratory tests that are 
graded for both low and high 
values, summaries will be done 
separately and labeled by direction. 
Include only 'worst-case post-
baseline'
SAC [A]
3.0321
All Treated
OLB9B
Summary of Hematology Grade Changes from Baseline Grade 
(Part 2 MM)
Report for: Part 2 MM, (Summarize: 
by starting dose level and tumor 
type, Total). Produce only for lab 
tests that are graded. For laboratory 
tests that are graded for both low 
and high values, summaries will be 
done separately and labeled by 
direction. Include only 'worst-case 
post-baseline'
SAC [A]
3.0322
All Treated
OLB9B
Summary of Hematology Grade Changes from Baseline Grade 
(All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Produce only 
for lab tests that are graded. For 
laboratory tests that are graded for 
both low and high values, 
summaries will be done separately 
and labeled by direction. Include 
only 'worst-case post-baseline'
SAC [A]


CONFIDENTIAL
BMA117159
180
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0323
All Treated
OLB9B
Summary of Hematology Grade Changes from Baseline Grade 
(Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: Total). Produce only 
for lab tests that are graded. For 
laboratory tests that are graded for 
both low and high values, 
summaries will be done separately 
and labeled by direction. Include 
only 'worst-case post-baseline'
SAC
Laboratory: Urinalysis
3.0360
All Treated
LB1
Summary of Urine Concentration Changes from Baseline (Part 
1)
Report for: Part 1, (Summarize by 
ascending dose level, Total). 
Include baseline values.
SAC [A]
3.0361
All Treated
LB1
Summary of Urine Concentration Changes from Baseline (Part 2 
MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Include baseline 
values.
SAC [A]
3.0362
All Treated
LB1
Summary of Urine Concentration Changes from Baseline (All 
Treated MM)
Report for: All Treated MM, 
(Summarize for Total). Include 
baseline values.
SAC [A]
3.0363
All Treated
LB1
Summary of Urine Concentration Changes from Baseline (Part 2 
NHL)
Report for: Part 2 NHL, (Summarize 
for Total). Include baseline values.
SAC
3.0680
All Treated
UR1
Summary of Worst Case Urinalysis Results (Discrete or 
Character Values) Post-Baseline Relative to Baseline (Part 1)
Report for: Part 1, (Summarize by 
ascending dose level, Total). 
Include baseline values.
SAC [A]
3.0681
All Treated
UR1
Summary of Worst Case Urinalysis Results (Discrete or 
Character Values) Post-Baseline Relative to Baseline (Part 2 
MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Include baseline 
values.
SAC [A]


CONFIDENTIAL
BMA117159
181
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0682
All Treated
UR1
Summary of Worst Case Urinalysis Results (Discrete or 
Character Values) Post-Baseline Relative to Baseline (All 
Treated MM)
Report for: All Treated MM, 
(Summarize for Total). Include 
baseline values.
SAC [A]
3.0683
All Treated
UR1
Summary of Worst Case Urinalysis Results (Discrete or 
Character Values) Post-Baseline Relative to Baseline (Part 2 
NHL)
Report for: Part 2 NHL, (Summarize 
for Total). Include baseline values.
SAC
Laboratory: Hepatobiliary (Liver)
3.0200
All Treated
LIVER1
Summary of Liver Monitoring/Stopping Event Reporting (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0201
All Treated
LIVER1
Summary of Liver Monitoring/Stopping Event Reporting (Part 2 
MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0202
All Treated
LIVER1
Summary of Liver Monitoring/Stopping Event Reporting (All 
Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0203
All Treated
LIVER1
Summary of Liver Monitoring/Stopping Event Reporting (Part 2 
NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0210
All Treated
LIVER10
Summary of Hepatobiliary Laboratory Abnormalities (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0211
All Treated
LIVER10
Summary of Hepatobiliary Laboratory Abnormalities (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0212
All Treated
LIVER10
Summary of Hepatobiliary Laboratory Abnormalities (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0213
All Treated
LIVER10
Summary of Hepatobiliary Laboratory Abnormalities (Part 2 
NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC


CONFIDENTIAL
BMA117159
182
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Laboratory: Coagulation
3.0330
All Treated
LB1
Summary of Coagulation Changes from Baseline (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0331
All Treated
LB1
Summary of Coagulation Changes from Baseline (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0332
All Treated
LB1
Summary of Coagulation Changes from Baseline (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0333
All Treated
LB1
Summary of Coagulation Changes from Baseline (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0340
All Treated
OLB11B
Summary of Coagulation Changes from Baseline with Respect 
to the Normal Range (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
Include only 'worst-case post-
baseline'
SAC [A]
3.0341
All Treated
OLB11B
Summary of Coagulation Changes from Baseline with Respect 
to the Normal Range (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Include only 
'worst-case post-baseline'
SAC [A]
3.0342
All Treated
OLB11B
Summary of Coagulation Changes from Baseline with Respect 
to the Normal Range (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Include only 
'worst-case post-baseline'
SAC [A]
3.0343
All Treated
OLB11B
Summary of Coagulation Changes from Baseline with Respect 
to the Normal Range (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL). 
Include only 'worst-case post-
baseline'
SAC
3.0350
All Treated
OLB9B
Summary of Coagulation Grade Changes from Baseline Grade 
(Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
Produce only for lab tests that are 
SAC [A]


CONFIDENTIAL
BMA117159
183
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
graded. For laboratory tests that are 
graded for both low and high 
values, summaries will be done 
separately and labeled by direction.
3.0351
All Treated
OLB9B
Summary of Coagulation Grade Changes from Baseline Grade 
(Part 2 MM)
Report for: Part 2 MM, (Summarize: 
by starting dose level and tumor 
type, Total). Produce only for lab 
tests that are graded. For laboratory 
tests that are graded for both low 
and high values, summaries will be 
done separately and labeled by 
direction.
SAC [A]
3.0352
All Treated
OLB9B
Summary of Coagulation Grade Changes from Baseline Grade 
(All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Produce only 
for lab tests that are graded. For 
laboratory tests that are graded for 
both low and high values, 
summaries will be done separately 
and labeled by direction.
SAC [A]
3.0353
All Treated
OLB9B
Summary of Coagulation Grade Changes from Baseline Grade 
(Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: Total). Produce only 
for lab tests that are graded. For 
laboratory tests that are graded for 
both low and high values, 
summaries will be done separately 
and labeled by direction.
SAC


CONFIDENTIAL
BMA117159
184
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
ECG
3.0370
All Treated
EG1
Summary of ECG Findings (Part 1)
Report for: Part 1, (Summarize by 
ascending dose level, Total). 
Include baseline values.
SAC [A]
3.0371
All Treated
EG1
Summary of ECG Findings (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Include baseline 
values.
SAC [A]
3.0372
All Treated
EG1
Summary of ECG Findings (All Treated MM)
Report for: All Treated MM, 
(Summarize for Total). Include 
baseline values.
SAC [A]
3.0373
All Treated
EG1
Summary of ECG Findings (Part 2 NHL)
Report for: All Treated MM, 
(Summarize for Total). Include 
baseline values.
SAC
3.0390
All Treated
OECG1B
Summary of Worst-case Increases in Fridericia's QTc (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
Include only 'worst-case post-
baseline'
SAC [A]
3.0391
All Treated
OECG1B
Summary of Worst-case Increases in Fridericia's QTc (Part 2 
MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM) Include only 'worst-
case post-baseline'
SAC [A]
3.0392
All Treated
OECG1B
Summary of Worst-case Increases in Fridericia's QTc (All 
Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Include only 
'worst-case post-baseline'
SAC [A]
3.0393
All Treated
OECG1B
Summary of Worst-case Increases in Fridericia's QTc (Part 2 
NHL)
Report for: Part 2 NHL, 
(Summarize: Total). Include only 
'worst-case post-baseline'
SAC


CONFIDENTIAL
BMA117159
185
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0400
All Treated
OECG2B
Summary of Worst-case Amount of Increase from Baseline 
Value in Fridericia's QTc (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
Include only 'worst-case post-
baseline'
SAC [A]
3.0401
All Treated
OECG2B
Summary of Worst-case Amount of Increase from Baseline 
Value in Fridericia's QTc (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM) Include only 'worst-
case post-baseline'
SAC [A]
3.0402
All Treated
OECG2B
Summary of Worst-case Amount of Increase from Baseline 
Value in Fridericia's QTc (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Include only 
'worst-case post-baseline'
SAC [A]
3.0403
All Treated
OECG2B
Summary of Worst-case Amount of Increase from Baseline 
Value in Fridericia's QTc (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: Total). Include only 
'worst-case post-baseline'
SAC
3.0380
All Treated
EG2
Summary of Change from Baseline in ECG Values by Visit (Part 
1)
Report for: Part 1, (Summarize by 
ascending dose level, Total). 
Include baseline values.
SAC [A]
3.0381
All Treated
EG2
Summary of Change from Baseline in ECG Values by Visit (Part 
2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM). Include baseline 
values.
SAC [A]
3.0382
All Treated
EG2
Summary of Change from Baseline in ECG Values by Visit (All 
Treated MM)
Report for: All Treated MM, 
(Summarize for Total). Include 
baseline values.
SAC [A]
3.0383
All Treated
EG2
Summary of Change from Baseline in ECG Values by Visit (Part 
2 NHL)
Report for: Part 2 NHL, (Summarize 
for Total). Include baseline values.
SAC


CONFIDENTIAL
BMA117159
186
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Vital Signs
3.0220
All Treated
VS1
Summary of Change from Baseline in Vital Signs (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). Add 
Cycle, Visit. Include baseline 
values.
SAC [A]
3.0221
All Treated
VS1
Summary of Change from Baseline in Vital Signs (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM) Add Cycle, Visit. 
Include baseline values.
SAC [A]
3.0222
All Treated
VS1
Summary of Change from Baseline in Vital Signs (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total). Add Cycle, 
Visit. Include baseline values.
SAC [A]
3.0223
All Treated
VS1
Summary of Change from Baseline in Vital Signs (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) Add 
Cycle, Visit. Include baseline 
values.
SAC
3.0230
All Treated
OVT1B
Summary of Changes in Heart Rate from Baseline (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
Include only 'worst-case post-
baseline'
SAC [A]
3.0231
All Treated
OVT1B
Summary of Changes in Heart Rate from Baseline (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM) Include only 'worst-
case post-baseline'
SAC [A]
3.0232
All Treated
OVT1B
Summary of Changes in Heart Rate from Baseline (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total). Include only 
'worst-case post-baseline'
SAC [A]


CONFIDENTIAL
BMA117159
187
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0233
All Treated
OVT1B
Summary of Changes in Heart Rate from Baseline (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) 
Include only 'worst-case post-
baseline'
SAC
3.0240
All Treated
OVT2B
Summary of Increases in Systolic Blood Pressure from Baseline 
(Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0241
All Treated
OVT2B
Summary of Increases in Systolic Blood Pressure from Baseline 
(Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0242
All Treated
OVT2B
Summary of Increases in Systolic Blood Pressure from Baseline 
(All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Include only 
'worst-case post-baseline'
SAC [A]
3.0243
All Treated
OVT2B
Summary of Increases in Systolic Blood Pressure from Baseline 
(Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) 
Include only 'worst-case post-
baseline'
SAC
3.0250
All Treated
OVT2B
Summary of Increases in Diastolic Blood Pressure from Baseline 
(Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
Include only 'worst-case post-
baseline'
SAC [A]
3.0251
All Treated
OVT2B
Summary of Increases in Diastolic Blood Pressure from Baseline 
(Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM) Include only 'worst-
case post-baseline'
SAC [A]
3.0252
All Treated
OVT2B
Summary of Increases in Diastolic Blood Pressure from Baseline 
(All Treated MM)
Report for: All Treated MM, 
(Summarize: Total). Include only 
'worst-case post-baseline'
SAC [A]


CONFIDENTIAL
BMA117159
188
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0253
All Treated
OVT2B
Summary of Increases in Diastolic Blood Pressure from Baseline 
(Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) 
Include only 'worst-case post-
baseline'
SAC
3.0260
All Treated
OVT1B
Summary of Changes in Temperature from Baseline (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total). 
Include only 'worst-case post-
baseline'
SAC [A]
3.0261
All Treated
OVT1B
Summary of Changes in Temperature from Baseline (Part 2 
MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM) Include only 'worst-
case post-baseline'
SAC [A]
3.0262
All Treated
OVT1B
Summary of Changes in Temperature from Baseline (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total). Include only 
'worst-case post-baseline'
SAC [A]
3.0263
All Treated
OVT1B
Summary of Changes in Temperature from Baseline (Part 2 
NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL) 
Include only 'worst-case post-
baseline'
SAC
ECOG Performance Status
3.0410
All Treated
PS1A
Summary of ECOG Performance Status (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0411
All Treated
PS1A
Summary of ECOG Performance Status (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0412
All Treated
PS1A
Summary of ECOG Performance Status (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]


CONFIDENTIAL
BMA117159
189
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0413
All Treated
PS1A
Summary of ECOG Performance Status (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0420
All Treated
PS3A
Summary of Change in ECOG Performance Status from 
Baseline (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0421
All Treated
PS3A
Summary of Change in ECOG Performance Status from 
Baseline (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0422
All Treated
PS3A
Summary of Change in ECOG Performance Status from 
Baseline (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0423
All Treated
PS3A
Summary of Change in ECOG Performance Status from 
Baseline (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
Left Ventricular Ejection Fraction
3.0480
All Treated
OLVEF1
A
Summary of Left Ventricular Ejection Fraction Change from 
Baseline (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0481
All Treated
OLVEF1
A
Summary of Left Ventricular Ejection Fraction Change from 
Baseline (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0482
All Treated
OLVEF1
A
Summary of Left Ventricular Ejection Fraction Change from 
Baseline (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0483
All Treated
OLVEF1
A
Summary of Left Ventricular Ejection Fraction Change from 
Baseline (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC


CONFIDENTIAL
BMA117159
190
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Ocular Exams
3.0490
All Treated
SAFE_T
1
Summary of Subjects Experiencing Corneal Clinical Signs (Part 
1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0491
All Treated
SAFE_T
1
Summary of Subjects Experiencing Corneal Clinical Signs (Part 
2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0492
All Treated
SAFE_T
1
Summary of Subjects Experiencing Corneal Clinical Signs (All 
Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0493
All Treated
SAFE_T
1
Summary of Subjects Experiencing Corneal Clinical Signs (Part 
2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0500
All Treated
SAFE_T
2
Summary of Best Corrected Visual Acuity Test (BCVA) Scores 
(logMAR score) (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0501
All Treated
SAFE_T
2
Summary of Best Corrected Visual Acuity Test (BCVA) Scores 
(logMAR score) (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0502
All Treated
SAFE_T
2
Summary of Best Corrected Visual Acuity Test (BCVA) Scores 
(logMAR score) (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0503
All Treated
SAFE_T
2
Summary of Best Corrected Visual Acuity Test (BCVA) Scores 
(logMAR score) (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
Death
3.0570
All Treated
DTH1a
Summary of Deaths (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0571
All Treated
DTH1a
Summary of Deaths (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0572
All Treated
DTH1a
Summary of Deaths (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]


CONFIDENTIAL
BMA117159
191
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
3.0573
All Treated
DTH1a
Summary of Deaths (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
Constitutional B- Symptoms
3.0813
All Treated
OCS1
Summary of Constitutional Symptoms over Time (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
Organ Examination
3.0823
All Treated
OOE1
Summary of Organ Examination over Time (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
Health Outcome
3.0830
All Treated
SAFE_T
3
Summary of Symptom Impact and HRQoL Item Scores (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0831
All Treated
SAFE_T
3
Summary of Symptom Impact and HRQoL Item Scores (Part 2 
MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0832
All Treated
SAFE_T
3
Summary of Symptom Impact and HRQoL Item Scores (All 
Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0833
All Treated
SAFE_T
3
Summary of Symptom Impact and HRQoL Item Scores (Part 2 
NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC


CONFIDENTIAL
BMA117159
192
Safety: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Anti-Drug Antibody
3.0840
All Treated
SAFE_T
4
Summary of Human Anti-GSK2857916 Antibodies (ADA) Over 
Time (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0841
All Treated
SAFE_T
4
Summary of Human Anti-GSK2857916 Antibodies (ADA) Over 
Time (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0842
All Treated
SAFE_T
4
Summary of Human Anti-GSK2857916 Antibodies (ADA) Over 
Time (All Treated MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0843
All Treated
SAFE_T
4
Summary of Human Anti-GSK2857916 Antibodies (ADA) Over 
Time (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
3.0850
All Treated
SAFE_T
5
Summary of Anti-GSK2857916 Antibodies (ADA) (Part 1)
Report for: Part 1, (Summarize: by 
ascending dose level, Total).
SAC [A]
3.0851
All Treated
SAFE_T
5
Summary of Anti-GSK2857916 Antibodies (ADA) (Part 2 MM)
Report for: Part 2 MM, (Summarize: 
only for 3.4 MM)
SAC [A]
3.0852
All Treated
SAFE_T
5
Summary of Anti-GSK2857916 Antibodies (ADA) (All Treated 
MM)
Report for: All Treated MM, 
(Summarize: Total).
SAC [A]
3.0853
All Treated
SAFE_T
5
Summary of Anti-GSK2857916 Antibodies (ADA) (Part 2 NHL)
Report for: Part 2 NHL, 
(Summarize: only for 3.4 NHL)
SAC
NOTES: 
A. Indicates which displays will be generated for the reporting effort for multiple myeloma


CONFIDENTIAL
BMA117159
193
16.12.9.
Safety Figures
Safety: Figures
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Laboratory
13.0130
All Treated
LIVER14
Scatter Plot of Maximum vs. Baseline for ALT (Part 1)
Report for sub-population: Part 1. 
Pool all subjects together.
SAC [A]
13.0131
All Treated
LIVER14
Scatter Plot of Maximum vs. Baseline for ALT (Part 2 MM)
Report for sub-population: Part 2 
MM.
SAC [A]
13.0133
All Treated
LIVER14
Scatter Plot of Maximum vs. Baseline for ALT (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
13.0120
All Treated
LIVER9
Scatter Plot of Maximum Bilirubin versus Maximum ALT -
eDISH (Part 1)
Report for sub-population: Part 1. 
Pool all subjects together.
SAC [A]
13.0121
All Treated
LIVER9
Scatter Plot of Maximum Bilirubin versus Maximum ALT -
eDISH (Part 2 MM)
Report for sub-population: Part 2 
MM.
SAC [A]
13.0122
All Treated
LIVER9
Scatter Plot of Maximum Bilirubin versus Maximum ALT -
eDISH (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC [A]
13.0140
All Treated
LIVER9
Scatter Plot of Maximum AST vs Maximum LDH - eDISH Plot 
(Part 1)
Report for sub-population: Part 1. 
Pool all subjects together. Bold 
reference lines are not needed. 
Do not include Hy's Quadrant and 
Temple's Corollary.
SAC [A]
13.0141
All Treated
LIVER9
Scatter Plot of Maximum AST vs Maximum LDH - eDISH Plot 
(Part 2 MM)
Report for sub-population: Part 2 
MM. Do not include Hy's Quadrant 
and Temple's Corollary.
SAC [A]


CONFIDENTIAL
BMA117159
194
Safety: Figures
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
13.0142
All Treated
LIVER9
Scatter Plot of Maximum AST vs Maximum LDH - eDISH Plot 
(Part 2 NHL)
Report for sub-population: Part 2 
NHL. Do not include Hy's 
Quadrant and Temple's Corollary.
SAC
13.0150
All Treated
LIVER9
Scatter Plot of Maximum AST vs Maximum Creatinine Kinase -
eDISH Plot (Part 1)
Report for sub-population: Part 1. 
Pool all subjects together. Bold 
reference lines are not needed. 
Do not include Hy's Quadrant and 
Temple's Corollary.
SAC [A]
13.0151
All Treated
LIVER9
Scatter Plot of Maximum AST vs Maximum Creatinine Kinase -
eDISH Plot (Part 2 MM)
Report for sub-population: Part 2 
MM. Do not include Hy's Quadrant 
and Temple's Corollary.
SAC [A]
13.0152
All Treated
LIVER9
Scatter Plot of Maximum AST vs Maximum Creatinine Kinase -
eDISH Plot (Part 2 NHL)
Report for sub-population: Part 2 
NHL. Do not include Hy's 
Quadrant and Temple's Corollary.
SAC
Adverse Events
13.0160
All Treated
SAFE_F1
Proportions of Subjects with Infusion-related Reactions (Part 1)
Report for sub-population: Part 1. 
Pool all subjects together.
SAC [A]
13.0161
All Treated
SAFE_F1
Proportions of Subjects with Infusion-related Reactions (Part 2 
MM)
Report for sub-population: Part 2 
MM.
SAC [A]
ECG
13.0200
All Treated
OECG4
Fridericia's QTc Shifts from Baseline to Worst-case Post 
Baseline (Part 1)
Report for sub-population: Part 1. 
Pool all subjects together. If 
machine read QTcF is missing, 
use the manual read QTcF and 
add footnote that Machine and 
Manual calculate values are 
SAC [A]


CONFIDENTIAL
BMA117159
195
Safety: Figures
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
collapsed together.
13.0201
All Treated
OECG4
Fridericia's QTc Shifts from Baseline to Worst-case Post 
Baseline (Part 2 MM)
Report for sub-population: Part 2 
MM. If machine read QTcF is 
missing, use the manual read 
QTcF, and add footnote that 
Machine and Manual calculate 
values are collapsed together
SAC [A]
13.0202
All Treated
OECG4
Fridericia's QTc Shifts from Baseline to Worst-case Post 
Baseline (Part 2 NHL)
Report for sub-population: Part 2 
NHL. If machine read QTcF is 
missing, use the manual read 
QTcF, and add footnote that 
Machine and Manual calculate 
values are collapsed together
SAC
Patient Profile Plot
13.0190
All Treated
SAFE_F2
Profile Plot for Patients with No Corneal Event or Grade 1 
Corneal Event (Part 2 MM)
Report for sub-population: Part 2 
MM.
SAC [A]
13.0191
All Treated
SAFE_F2
Profile Plot for Patients with Grade 2 or Higher Corneal Events 
(Part 2 MM) 
Report for sub-population: Part 2 
MM.
SAC [A]
NOTES: 
A. Indicates which displays will be generated for the reporting effort for multiple myeloma


CONFIDENTIAL
BMA117159
196
16.12.10. Pharmacokinetic Tables
Pharmacokinetic: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Concentration
4.0010
PK
PK01
Summary of Plasma GSK2857916 (ADC) PK Concentration-
Time Data (Part 1)
By dose level
SAC [A]
4.0011
PK
PK01
Summary of Plasma GSK2857916 (ADC) PK Concentration-
Time Data (Part 2 MM)
SAC [A]
4.0013
PK
PK01
Summary of Plasma GSK2857916 (ADC) PK Concentration-
Time Data (Part 2 NHL)
SAC
4.0020
PK
PK01
Summary of Plasma GSK2857916 (Total Antibody) PK 
Concentration-Time Data (Part 1)
By dose level
SAC [A]
4.0021
PK
PK01
Summary of Plasma GSK2857916 (Total Antibody) PK 
Concentration-Time Data (Part 2 MM)
SAC [A]
4.0023
PK
PK01
Summary of Plasma GSK2857916 (Total Antibody) PK
Concentration-Time Data (Part 2 NHL)
SAC
4.0030
PK
PK01
Summary of Plasma GSK2857916 (Unbound Antibody) PK 
Concentration-Time Data (Part 1)
By dose level
SAC [A]
4.0031
PK
PK01
Summary of Plasma GSK2857916 (Unbound Antibody) PK 
Concentration-Time Data (Part 2 MM)
If data was not collected, present “No 
data to report”
SAC [A]
4.0033
PK
PK01
Summary of Plasma GSK2857916 (Unbound Antibody) PK 
Concentration-Time Data (Part 2 NHL)
If data was not collected, present “No 
data to report”
SAC
4.0040
PK
PK01
Summary of Plasma cys-mcMMAF PK Concentration-Time 
Data (Part 1)
By dose level
SAC [A]


CONFIDENTIAL
BMA117159
197
Pharmacokinetic: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
4.0041
PK
PK01
Summary of Plasma cys-mcMMAF PK Concentration-Time 
Data (Part 2 MM)
SAC [A]
4.0043
PK
PK01
Summary of Plasma cys-mcMMAF PK Concentration-Time 
Data (Part 2 NHL)
SAC
PK Parameter
4.0050
PK
PK06
Summary of Derived GSK2857916 (ADC) PK Parameters 
(Part 1)
By dose level
PK06 with both transformed and 
untransformed values. Also 
include Cmax and Ctau derived 
for ratio analyses.
SAC [A]
4.0051
PK
PK06
Summary of Derived GSK2857916 (ADC) PK Parameters 
(Part 2 MM)
PK06 with both transformed and 
untransformed values. Cmax and 
Ctau
SAC [A]
4.0053
PK
PK06
Summary of Derived GSK2857916 (ADC) PK Parameters 
(Part 2 NHL)
PK06 with both transformed and 
untransformed values. Cmax and 
Ctau
SAC
4.0060
PK
PK06
Summary of Derived GSK2857916 (Total Antibody) PK 
Parameters (Part 1)
By dose level
PK06 with both transformed and 
untransformed values. Also 
include Cmax and Ctau derived 
for ratio analyses.
SAC [A]
4.0061
PK
PK06
Summary of Derived GSK2857916 (Total Antibody) PK 
Parameters (Part 2 MM)
PK06 with both transformed and 
untransformed values. Cmax and 
Ctau
SAC [A]


CONFIDENTIAL
BMA117159
198
Pharmacokinetic: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
4.0063
PK
PK06
Summary of Derived GSK2857916 (Total Antibody) PK 
Parameters (Part 2 NHL)
PK06 with both transformed and 
untransformed values. Cmax and 
Ctau
SAC
4.0070
PK
PK06
Summary of Derived GSK2857916 (Unbound Antibody) PK 
Parameters (Part 1)
By dose level
PK06 with both transformed and 
untransformed values. Also 
include Cmax and Ctau derived 
for ratio analyses.
SAC [A]
4.0071
PK
PK06
Summary of Derived GSK2857916 (Unbound Antibody) PK 
Parameters (Part 2 MM)
PK06 with both transformed and 
untransformed values. Cmax and 
Ctau. If data was not collected, 
present “No data to report”
SAC [A]
4.0073
PK
PK06
Summary of Derived GSK2857916 (Unbound Antibody) PK 
Parameters (Part 2 NHL)
PK06 with both transformed and 
untransformed values. Cmax and 
Ctau. If data was not collected, 
present “No data to report”
SAC
4.0080
PK
PK06
Summary of Derived cys-mcMMAF PK Parameter (Part 1)
By dose level
PK06 with both transformed and 
untransformed values. Also 
include Cmax and Ctau derived 
for ratio analyses.
SAC [A]
4.0081
PK
PK06
Summary of Derived cys-mcMMAF PK Parameter (Part 2 MM)
PK06 with both transformed and 
untransformed values. Cmax and 
Ctau
SAC [A]


CONFIDENTIAL
BMA117159
199
Pharmacokinetic: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
4.0083
PK
PK06
Summary of Derived cys-mcMMAF PK Parameter (Part 2 
NHL)
PK06 with both transformed and 
untransformed values. Cmax and 
Ctau
SAC
4.0090
PK
PK13
Listing of Derived GSK2857916 (ADC) PK Parameters 
(Untransformed) (MM)
SAC [A]
4.0091
PK
PK13
Listing of Derived GSK2857916 (ADC) PK Parameters 
(Untransformed) (NHL)
SAC
4.0100
PK
PK13
Listing of Derived GSK2857916 (Total Antibody) PK 
Parameters (Untransformed) (MM)
SAC [A]
4.0101
PK
PK13
Listing of Derived GSK2857916 (Total Antibody) PK 
Parameters (Untransformed) (NHL)
SAC
4.0110
PK
PK13
Listing of Derived GSK2857916 (Unbound Antibody) PK 
Parameters (Untransformed) (MM)
SAC [A]
4.0111
PK
PK13
Listing of Derived GSK2857916 (Unbound Antibody) PK 
Parameters (Untransformed) (NHL)
SAC
4.0120
PK
PK13
Listing of Derived cys-mcMMAF PK Parameters 
(Untransformed) (MM)
SAC [A]
4.0121
PK
PK13
Listing of Derived cys-mcMMAF PK Parameters 
(Untransformed) (NHL)
SAC
4.0130
PK
PK03
Summary of cys-mcMMAF Pharmacokinetic Urine Excretin 
Data (Part 1)
SAC [A]
4.0140
PK
PK11
Listing of cys-mcMMAF Urine Excretion Data (Part 1)
replace Amount Excreted and 
Excretion Rate with Ae(0-24) and 
Fe
SAC [A]


CONFIDENTIAL
BMA117159
200
Pharmacokinetic: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Dose Proportionality Analysis
4.0150
PK
PK_T1
Summary of Results of Dose Proportionality Analysis for 
GSK2857916 (ADC), GSK2857916 (Total Antibody), 
GSL2857916 (Unbound Antibody), and cys-mcMMAF PK 
Parameters Using Power Model (Part 1)
Example:
AUC(0-inf), AUC(0-t), AUC(0- τ), Cmax, and 
Ctrough
SAC [A]
Accumulation Ratio
4.0160
PK
PK_T2
Summary of Results of Accumulation Ratio Assessment for 
GSK2857916 (ADC) PK Parameter Cmax on Day 1 of Cycle 
2, 3, 5 verses Cmax on Day 1 of Cycle 1 (Part 1)
By dose level
SAC [A]
4.0161
PK
PK_T2
Summary of Results of Accumulation Ratio Assessment for 
GSK2857916 (ADC) PK Parameter Cmax on Day 1 of Cycle 
2, 3, 5 verses Cmax on Day 1 of Cycle 1 (Part 2 MM)
SAC [A]
4.0163
PK
PK_T2
Summary of Results of Accumulation Ratio Assessment for 
GSK2857916 (ADC) PK Parameter Cmax on Day 1 of Cycle 
2, 3, 5 verses Cmax on Day 1 of Cycle 1 (Part 2 NHL)
SAC
4.0170
PK
PK_T2
Summary of Results of Accumulation Ratio Assessment for 
GSK2857916 (Total Antibody) PK Parameter Cmax on Day 1 
of Cycle 2, 3, 5 verses Cmax on Day 1 of Cycle 1 (Part 1)
By dose
SAC [A]
4.0171
PK
PK_T2
Summary of Results of Accumulation Ratio Assessment for 
GSK2857916 (Total Antibody) PK Parameter Cmax on Day 1 
of Cycle 2, 3, 5 verses Cmax on Day 1 of Cycle 1 (Part 2 MM)
SAC [A]
4.0173
PK
PK_T2
Summary of Results of Accumulation Ratio Assessment for 
GSK2857916 (Total Antibody) PK Parameter Cmax on Day 1 
of Cycle 2, 3, 5 verses Cmax on Day 1 of Cycle 1 (Part 2 NHL)
SAC
PPD
PPD


CONFIDENTIAL
BMA117159
201
Pharmacokinetic: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
4.0180
PK
PK_T2
Summary of Results of Accumulation Ratio Assessment for 
GSK2857916 (Unbound Antibody) PK Parameter Cmax on 
Day 1 of Cycle 2, 3, 5 verses Cmax on Day 1 of Cycle 1 (Part 
1)
By dose
SAC [A]
4.0181
PK
PK_T2
Summary of Results of Accumulation Ratio Assessment for 
GSK2857916 (Unbound Antibody) PK Parameter Cmax on 
Day 1 of Cycle 2, 3, 5 verses Cmax on Day 1 of Cycle 1 (Part 
2 MM)
If data was not collected, present “No 
data to report”
SAC [A]
4.0183
PK
PK_T2
Summary of Results of Accumulation Ratio Assessment for 
GSK2857916 (Unbound Antibody) PK Parameter Cmax on 
Day 1 of Cycle 2, 3, 5 verses Cmax on Day 1 of Cycle 1 (Part 
2 NHL)
If data was not collected, present “No 
data to report”
SAC
4.0190
PK
PK_T2
Summary of Results of Accumulation Ratio Assessment for 
cys-mcMMAF PK Parameter Cmax on Day 1 of Cycle 2, 3, 5 
verses Cmax on Day 1 of Cycle 1 (Part 1)
By dose level
SAC [A]
4.0191
PK
PK_T2
Summary of Results of Accumulation Ratio Assessment for 
cys-mcMMAF PK Parameter Cmax on Day 1 of Cycle 2, 3, 5 
verses Cmax on Day 1 of Cycle 1 (Part 2 MM)
SAC [A]
4.0193
PK
PK_T2
Summary of Results of Accumulation Ratio Assessment for 
cys-mcMMAF PK Parameter Cmax on Day 1 of Cycle 2, 3, 5 
verses Cmax on Day 1 of Cycle 1 (Part 2 NHL)
SAC
4.0200
PK
PK_T2
Summary of Results of Accumulation Ratio Assessment for 
GSK2857916 (ADC) PK Parameter Ctrough on Day 1 of Cycle 
2, 3, 5 verses Ctrough on Day 1 of Cycle 1 (Part 1)
By dose level
SAC [A]


CONFIDENTIAL
BMA117159
202
Pharmacokinetic: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
4.0201
PK
PK_T2
Summary of Results of Accumulation Ratio Assessment for 
GSK2857916 (ADC) PK Parameter Ctrough on Day 1 of Cycle 
2, 3, 5 verses Ctrough on Day 1 of Cycle 1 (Part 2 MM)
SAC [A]
4.0203
PK
PK_T2
Summary of Results of Accumulation Ratio Assessment for 
GSK2857916 (ADC) PK Parameter Ctrough on Day 1 of Cycle 
2, 3, 5 verses Ctrough on Day 1 of Cycle 1 (Part 2 NHL)
SAC
4.0210
PK
PK_T2
Summary of Results of Accumulation Ratio Assessment for 
GSK2857916 (Total Antibody) PK Parameter Ctrough on Day 
1 of Cycle 2, 3, 5 verses Ctrough on Day 1 of Cycle 1 (Part 1)
By dose
SAC [A]
4.0211
PK
PK_T2
Summary of Results of Accumulation Ratio Assessment for 
GSK2857916 (Total Antibody) PK Parameter Ctrough on Day 
1 of Cycle 2, 3, 5 verses Ctrough on Day 1 of Cycle 1 (Part 2 
MM)
SAC [A]
4.0213
PK
PK_T2
Summary of Results of Accumulation Ratio Assessment for 
GSK2857916 (Total Antibody) PK Parameter Ctrough on Day 
1 of Cycle 2, 3, 5 verses Ctrough on Day 1 of Cycle 1 (Part 2 
NHL)
SAC
4.0220
PK
PK_T2
Summary of Results of Accumulation Ratio Assessment for 
GSK2857916 (Unbound Antibody) PK Parameter Ctrough on 
Day 1 of Cycle 2, 3, 5 verses Ctrough on Day 1 of Cycle 1 
(Part 1)
By dose
SAC [A]
4.0221
PK
PK_T2
Summary of Results of Accumulation Ratio Assessment for 
GSK2857916 (Unbound Antibody) PK Parameter Ctrough on 
Day 1 of Cycle 2, 3, 5 verses Ctrough on Day 1 of Cycle 1 
(Part 2 MM)
If data was not collected, present “No 
data to report”
SAC [A]


CONFIDENTIAL
BMA117159
203
Pharmacokinetic: Tables
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
4.0223
PK
PK_T2
Summary of Results of Accumulation Ratio Assessment for 
GSK2857916 (Unbound Antibody) PK Parameter Ctrough on 
Day 1 of Cycle 2, 3, 5 verses Ctrough on Day 1 of Cycle 1 
(Part 2 NHL)
If data was not collected, present “No 
data to report”
SAC
4.0230
PK
PK_T2
Summary of Results of Accumulation Ratio Assessment for 
cys-mcMMAF PK Parameter Ctrough on Day 1 of Cycle 2, 3, 
5 verses Ctrough on Day 1 of Cycle 1 (Part 1)
By dose
SAC [A]
4.0231
PK
PK_T2
Summary of Results of Accumulation Ratio Assessment for 
cys-mcMMAF PK Parameter Ctrough on Day 1 of Cycle 2, 3, 
5 verses Ctrough on Day 1 of Cycle 1 (Part 2 MM)
SAC [A]
4.0233
PK
PK_T2
Summary of Results of Accumulation Ratio Assessment for 
cys-mcMMAF PK Parameter Ctrough on Day 1 of Cycle 2, 3, 
5 verses Ctrough on Day 1 of Cycle 1 (Part 2 NHL)
SAC
NOTES: 
A. Indicates which displays will be generated for the reporting effort for multiple myeloma


CONFIDENTIAL
BMA117159
204
16.12.11. Pharmacokinetic Figures
Pharmacokinetic: Figures
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Concentration
14.0010
PK
PK16
Individual Plasma GSK2857916 (ADC) Concentration-Time 
Plots (Linear and Semi-Log) (Part 1)
SAC [A]
14.0011
PK
PK16
Individual Plasma GSK2857916 (ADC) Concentration-Time 
Plots (Linear and Semi-Log) (Part 2 MM)
SAC [A]
14.0013
PK
PK16
Individual Plasma GSK2857916 (ADC) Concentration-Time 
Plots (Linear and Semi-Log) (Part 2 NHL)
SAC
14.0020
PK
PK16
Individual Plasma GSK2857916 (Total Antibody) 
Concentration-Time Plots (Linear and Semi-Log) (Part 1)
SAC [A]
14.0021
PK
PK16
Individual Plasma GSK2857916 (Total Antibody) 
Concentration-Time Plots (Linear and Semi-Log) (Part 2 MM)
SAC [A]
14.0023
PK
PK16
Individual Plasma GSK2857916 (Total Antibody) 
Concentration-Time Plots (Linear and Semi-Log) (Part 2 NHL)
SAC
14.0030
PK
PK16
Individual Plasma GSK2857916 (Unbound Antibody) 
Concentration-Time Plots (Linear and Semi-Log) (Part 1)
SAC [A]
14.0031
PK
PK16
Individual Plasma GSK2857916 (Unbound Antibody) 
Concentration-Time Plots (Linear and Semi-Log) (Part 2 MM)
If data was not collected, present “No 
data to report”
SAC [A]
14.0033
PK
PK16
Individual Plasma GSK2857916 (Unbound Antibody) 
Concentration-Time Plots (Linear and Semi-Log) (Part 2 NHL)
If data was not collected, present “No 
data to report”
SAC
14.0040
PK
PK16
Individual Plasma cys-mcMMAF Concentration-Time Plots 
(Linear and Semi-Log) (Part 1)
SAC [A]


CONFIDENTIAL
BMA117159
205
Pharmacokinetic: Figures
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
14.0041
PK
PK16
Individual Plasma cys-mcMMAF Concentration-Time Plots 
(Linear and Semi-Log) (Part 2 MM)
SAC [A]
14.0043
PK
PK16
Individual Plasma cys-mcMMAF Concentration-Time Plots 
(Linear and Semi-Log) (Part 2 NHL)
SAC
14.0050
PK
PK17
Mean Plasma GSK2857916 (ADC) Concentration-Time Plots 
(Linear and Semi-Log) (Part 1)
SAC [A]
14.0051
PK
PK17
Mean Plasma GSK2857916 (ADC) Concentration-Time Plots 
(Linear and Semi-Log) (Part 2 MM)
SAC [A]
14.0053
PK
PK17
Mean Plasma GSK2857916 (ADC) Concentration-Time Plots 
(Linear and Semi-Log) (Part 2 NHL)
SAC
14.0060
PK
PK17
Mean Plasma GSK2857916 (Total Anti-body) Concentration-
Time Plots (Linear and Semi-Log) (Part 1)
SAC [A]
14.0061
PK
PK17
Mean Plasma GSK2857916 (Total Anti-body) Concentration-
Time Plots (Linear and Semi-Log) (Part 2 MM)
SAC [A]
14.0063
PK
PK17
Mean Plasma GSK2857916 (Total Anti-body) Concentration-
Time Plots (Linear and Semi-Log) (Part NHL)
SAC
14.0070
PK
PK17
Mean Plasma GSK2857916 (Unbound Anti-body) 
Concentration-Time Plots (Linear and Semi-Log) (Part 1)
SAC [A]
14.0071
PK
PK17
Mean Plasma GSK2857916 (Unbound Anti-body) 
Concentration-Time Plots (Linear and Semi-Log) (Part 2 MM)
If data was not collected, present “No 
data to report”
SAC [A]
14.0073
PK
PK17
Mean Plasma GSK2857916 (Unbound Anti-body) 
Concentration-Time Plots (Linear and Semi-Log) (Part 2 NHL)
If data was not collected, present “No 
data to report”
SAC
14.0080
PK
PK17
Mean Plasma GSK2857916 (cys-mcMMAF) Concentration-
Time Plots (Linear and Semi-Log) (Part 1)
SAC [A]


CONFIDENTIAL
BMA117159
206
Pharmacokinetic: Figures
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
14.0081
PK
PK17
Mean Plasma GSK2857916 (cys-mcMMAF) Concentration-
Time Plots (Linear and Semi-Log) (Part 2 MM)
SAC [A]
14.0083
PK
PK17
Mean Plasma GSK2857916 (cys-mcMMAF) Concentration-
Time Plots (Linear and Semi-Log) (Part 2 NHL)
SAC
14.0090
PK
PK18
Median Plasma GSK2857916 (ADC) Concentration-Time 
Plots (Linear and Semi-Log) (Part 1)
SAC [A]
14.0091
PK
PK18
Median Plasma GSK2857916 (ADC) Concentration-Time 
Plots (Linear and Semi-Log) (Part 2 MM)
SAC [A]
14.0093
PK
PK18
Median Plasma GSK2857916 (ADC) Concentration-Time 
Plots (Linear and Semi-Log) (Part 2 NHL)
SAC
14.0100
PK
PK18
Median Plasma GSK2857916 (Total Anti-body) 
Concentration-Time Plots (Linear and Semi-Log) (Part 1)
SAC [A]
14.0101
PK
PK18
Median Plasma GSK2857916 (Total Anti-body) 
Concentration-Time Plots (Linear and Semi-Log) (Part 2 MM)
SAC [A]
14.0103
PK
PK18
Median Plasma GSK2857916 (Total Anti-body) 
Concentration-Time Plots (Linear and Semi-Log) (Part 2 NHL)
SAC
14.0110
PK
PK18
Median Plasma GSK2857916 (Unbound Anti-body) 
Concentration-Time Plots (Linear and Semi-Log) (Part 1)
SAC [A]
14.0111
PK
PK18
Median Plasma GSK2857916 (Unbound Anti-body) 
Concentration-Time Plots (Linear and Semi-Log) (Part 2 MM)
If data was not collected, present “No 
data to report”
SAC [A]
14.0113
PK
PK18
Median Plasma GSK2857916 (Unbound Anti-body) 
Concentration-Time Plots (Linear and Semi-Log) (Part 2 NHL)
If data was not collected, present “No 
data to report”
SAC
14.0120
PK
PK18
Median Plasma GSK2857916 (cys-mcMMAF) Concentration-
Time Plots (Linear and Semi-Log) (Part 1)
SAC [A]


CONFIDENTIAL
BMA117159
207
Pharmacokinetic: Figures
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
14.0121
PK
PK18
Median Plasma GSK2857916 (cys-mcMMAF) Concentration-
Time Plots (Linear and Semi-Log) (Part 2 MM)
SAC [A]
14.0123
PK
PK18
Median Plasma GSK2857916 (cys-mcMMAF) Concentration-
Time Plots (Linear and Semi-Log) (Part 2 NHL)
SAC
Dose Proportionality
14.0130
PK
LIVER14
Scatter Plot of GSK2857916 (ADC), GSK2857916 (Total 
Antibody), GSK2857916 (Unbound Antibody), and cys-
mcMMAF PK Parameters by Cycle 1 Dose (Part 1)
using log transformed value. for 
AUC(0-tau), Cmax, 
PK Parameter value as y-axis and 
Cycle 1 dose as x-axis; label x-axis 
with dose value. Use the format of 
mock up LIVER14, no reference line 
is needed.
SAC [A]
Accumulation Ratio
14.0140
PK
PK_F1
Plot of Mean Accumulation Ratios for GSK2857916 Analytes 
(Linear and Semi-Log) (Part 1)
See example in page 7 of
By dose level
PRE: Ctau
EOI: Cmax
Add a reference line at 1
Plot Ro for Ctau and Cmax on 
SAC [A]
PPD


CONFIDENTIAL
BMA117159
208
Pharmacokinetic: Figures
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
different plots.
Use “Ratio to C1 (EOI)” as y-axis 
label for Cmax; Use “Ratio to C1 
(PRE)” as y-axis label for Ctau;
Plot analytes: ADC, total antibody, 
unbound antibody, and cys-mcMMAF 
on the same plot.
14.0141
PK
PK_F1
Plot of Mean Accumulation Ratios for GSK2857916 Analytes 
(Linear and Semi-Log) (Part 2 MM)
Add a reference line at 1
SAC [A]
14.0142
PK
PK_F1
Plot of Mean Accumulation Ratios for GSK2857916 Analytes 
(Linear and Semi-Log) (Part 2 NHL)
Add a reference line at 1
SAC
Analyte Ratio at Each Cycle 1
14.0180
PK
PK_F1
Plot of Mean Analyte Ratios for GSK2857916 Analytes (Linear 
and Semi-Log) (Part 1)
See example in Page 6 of 
By dose
PRE: Ctau
EOI: Cmax
Plot Ra for Ctau and Cmax on the 
same plot.
Use “Analyte Ratio to cys-mcMMAF” 
as y-axis label
SAC [A]
PPD


CONFIDENTIAL
BMA117159
209
Pharmacokinetic: Figures
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
14.0181
PK
PK_F1
Plot of Mean Analyte Ratios for GSK2857916 Analytes (Linear 
and Semi-Log) (Part 2 MM)
SAC [A]
14.0182
PK
PK_F1
Plot of Mean Analyte Ratios for GSK2857916 Analytes (Linear 
and Semi-Log) (Part 2 NHL)
SAC
NOTES: 
A. Indicates which displays will be generated for the reporting effort for multiple myeloma


CONFIDENTIAL
BMA117159
210
16.12.12. Pharmacokinetic / Pharmacodynamic (and / or Biomarker) Figures
Pharmacokinetic / Pharmacodynamic: Figures
No.
Population
IDSL /
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
16.0010
PK/PD
PK_F2
Plot of Fridericia’s QTc Change from Baseline versus PK 
Concentration for GSK2857916 (ADC) (MM)
SAC [A]
16.0011
PK/PD
PK_F2
Plot of Fridericia’s QTc Change from Baseline versus PK 
Concentration for GSK2857916 (ADC) (NHL)
SAC
16.0020
PK/PD
PK_F2
Plot of Fridericia’s QTc Change from Baseline versus PK 
Concentration for GSK2857916 (Total Antibody) (MM)
SAC [A]
16.0021
PK/PD
PK_F2
Plot of Fridericia’s QTc Change from Baseline versus PK 
Concentration for GSK2857916 (Total Antibody) (NHL)
SAC
16.0030
PK/PD
PK_F2
Plot of Fridericia’s QTc Change from Baseline versus PK 
Concentration for GSK2857916 (Unbound Antibody) (MM)
SAC [A]
16.0031
PK/PD
PK_F2
Plot of Fridericia’s QTc Change from Baseline versus PK 
Concentration for GSK2857916 (Unbound Antibody) (NHL)
If data was not collected, present “No 
data to report”
SAC
16.0040
PK/PD
PK_F2
Plot of Fridericia’s QTc Change from Baseline versus PK 
Concentration for cys-mcMMAF (MM)
SAC [A]
16.0041
PK/PD
PK_F2
Plot of Fridericia’s QTc Change from Baseline versus PK 
Concentration for cys-mcMMAF (NHL)
SAC
NOTES: 
A. Indicates which displays will be generated for the reporting effort for multiple myeloma


CONFIDENTIAL
BMA117159
211
16.12.13. ICH Listings
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Subject Disposition
1.0010
All Treated
ES2
Listing of Reasons for Study Withdrawal (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0011
All Treated
ES2
Listing of Reasons for Study Withdrawal (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
1.0020
All Treated
CP_RA1p
Listing of Planned and Actual Treatments (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0021
All Treated
CP_RA1p
Listing of Planned and Actual Treatments (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
1.0030
All Treated
SD2
Listing of Reasons for Study Treatment Discontinuation (All 
Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0031
All Treated
SD2
Listing of Reasons for Study Treatment Discontinuation (Part 2 
NHL)
Report for sub-population: Part 2 
NHL.
SAC
1.0750
Screened
ES7
Listing of Reasons for Screen Failure (MM)
Report for multiple myeloma 
subjects screened
SAC [A]
1.0751
Screened
ES7
Listing of Reasons for Screen Failure (NHL)
Report for lymphoma subjects 
screened
SAC
Protocol Deviations
1.0040
All Treated
DV2
Listing of Important Protocol Deviations (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0041
All Treated
DV2
Listing of Important Protocol Deviations (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC


CONFIDENTIAL
BMA117159
212
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0050
All Treated
IE3
Listing of Subjects with Inclusion/Exclusion Criteria Deviations 
(All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0051
All Treated
IE3
Listing of Subjects with Inclusion/Exclusion Criteria Deviations 
(Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
Populations Analysed
1.0060
All Treated
SA3a
Listing of Subjects Excluded from Any Population (All Treated 
MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0061
All Treated
SA3a
Listing of Subjects Excluded from Any Population (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
Demographic and Baseline Characteristics
1.0070
All Treated
DM2
Listing of Demographic Characteristics (All Treated MM)
Report for sub-population: All 
Treated MM. Add BMI (kg/m2).
SAC [A]
1.0071
All Treated
DM2
Listing of Demographic Characteristics (Part 2 NHL)
Report for sub-population: Part 2 
NHL. Add BMI (kg/m2).
SAC
1.0080
All Treated
DM9
Listing of Race (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0081
All Treated
DM9
Listing of Race (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
Prior and Concomitant Medications
1.0620
All Treated
OCM1A
Listing of Concomitant Medications (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0621
All Treated
OCM1A
Listing of Concomitant Medications (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC


CONFIDENTIAL
BMA117159
213
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Exposure and Treatment Compliance
1.0090
All Treated
OEX8A
Listing of Exposure Data (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0091
All Treated
OEX8A
Listing of Exposure Data (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
1.0100
All Treated
ODMOD10A
Listing of Dose Reductions (All Treated MM)
Report for sub-population: All 
Treated MM. Include Planned 
Time. 
SAC [A]
1.0101
All Treated
ODMOD10A
Listing of Dose Reductions (Part 2 NHL)
Report for sub-population: All 
Treated MM. Include Planned 
Time. 
SAC
1.0110
All Treated
ODMOD12A
Listing of Dose Delays (All Treated MM)
Report for sub-population: All 
Treated MM. Include Planned 
Time. IDSL standard does not 
report demographic info.  
 to check with
 regarding planned time and 
cycle day. If it is too much 
programming work to change now, 
we can keep it as it is.
SAC [A]
PPD
PPD
PPD


CONFIDENTIAL
BMA117159
214
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0111
All Treated
ODMOD12A
Listing of Dose Delays (Part 2 NHL)
Report for sub-population: All 
Treated MM. Include Planned 
Time. IDSL standard does not 
report demographic info.  
 to check with
 
regarding planned time and 
cycle day. If it is too much 
programming work to change now, 
we can keep it as it is.
SAC
1.0120
All Treated
ODMOD15A
Listing of Dose Escalations (All Treated MM)
Report for sub-population: All 
Treated MM. Include 
Age(y)/Sex/Race, Cycle, Visit.
For C2MD, list the dose 
escalations where a dose 
escalation is indicated in the data –
from the site.
SAC [A]
1.0121
All Treated
ODMOD15A
Listing of Dose Escalations (Part 2 NHL)
Report for sub-population: All 
Treated MM. Include 
Age(y)/Sex/Race, Cycle, Visit.
For C2MD, list the dose 
escalations where a dose 
escalation is indicated in the data –
from the site.
SAC
1.0490
All Treated
ODMOD14A
Listing of Incomplete Infusions (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0491
All Treated
ODMOD14A
Listing of Incomplete Infusions (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
PPD
PPD
PPD


CONFIDENTIAL
BMA117159
215
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0500
All Treated
ODMOD17A
Listing of Infusion Interruptions (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0501
All Treated
ODMOD17A
Listing of Infusion Interruptions (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
Adverse Events
1.0140
All Treated
OAE04
Listing of All Adverse Events (All Treated MM)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
SAC [A]
1.0141
All Treated
OAE04
Listing of All Adverse Events (Part 2 NHL)
Report for population subgroup: 
Part 2 NHL. Remove onset cycle 
and cycle day from all AE related 
listings.
SAC
1.0150
All Treated
OAE03
Listing of Subject Numbers for Individual Adverse Events (All 
Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0151
All Treated
OAE03
Listing of Subject Numbers for Individual Adverse Events (Part 
2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
1.0160
All Treated
AE2
Listing of Relationship Between Adverse Event System Organ 
Classes, Preferred Terms, and Verbatim Text (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0161
All Treated
AE2
Listing of Relationship Between Adverse Event System Organ 
Classes, Preferred Terms, and Verbatim Text (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC


CONFIDENTIAL
BMA117159
216
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Serious and Other Significant Adverse Events
1.0180
All Treated
OAE04
Listing of Fatal Serious Adverse Events (All Treated MM)
Report for sub-population: All 
Treated MM. Include column to 
indicate relationship to study 
treatment.
SAC [A]
1.0181
All Treated
OAE04
Listing of Fatal Serious Adverse Events (Part 2 NHL)
Report for sub-population: All 
Treated MM. Include column to 
indicate relationship to study 
treatment.
SAC
1.0190
All Treated
OAE04
Listing of Non-Fatal Serious Adverse Events (All Treated MM)
Report for sub-population: All 
Treated MM. Include column to 
indicate relationship to study 
treatment.
SAC [A]
1.0191
All Treated
OAE04
Listing of Non-Fatal Serious Adverse Events (Part 2 NHL)
Report for sub-population: All 
Treated MM. Include column to 
indicate relationship to study 
treatment.
SAC
1.0460
All Treated
AE14
Listing of Reasons for Considering as a Serious Adverse Event 
(All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0461
All Treated
AE14
Listing of Reasons for Considering as a Serious Adverse Event 
(Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
1.0470
All Treated
OAE04
Listing of Adverse Events Leading to Withdrawal from Study / 
Permanent Discontinuation of Study Treatment (All Treated 
MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0471
All Treated
OAE04
Listing of Adverse Events Leading to Withdrawal from Study / 
Permanent Discontinuation of Study Treatment (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC


CONFIDENTIAL
BMA117159
217
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0200
All Treated
OAE04
Listing of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment (All Treated MM)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
SAC [A]
1.0201
All Treated
OAE04
Listing of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment (Part 2 NHL)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
SAC
1.0210
All Treated
OAE04
Listing of Dose-Limiting Adverse Events (All Treated MM)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
SAC [A]
1.0220
DLT 
Evaluable
DL3
Listing of Dose-Limiting Toxicities during the Determinative
Period (Day 1-21) (Part 1) 
Report for population subgroup: 
Part 1
SAC [A]
1.0240
All Treated
OAE04
Listing of Adverse Events Leading to Dose Reduction (All 
Treated MM)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
SAC [A]
1.0241
All Treated
OAE04
Listing of Adverse Events Leading to Dose Reduction (Part 2 
NHL)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
SAC
1.0250
All Treated
OAE04
Listing of Adverse Events Leading to Dose Interruptions or 
Delays (All Treated MM)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
SAC [A]


CONFIDENTIAL
BMA117159
218
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0251
All Treated
OAE04
Listing of Adverse Events Leading to Dose Interruptions or 
Delays (Part 2 NHL)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
SAC
1.0510
All Treated
OAE04
Listing of Adverse Events Leading to Incomplete Infusions (All 
Treated MM)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
SAC [A]
1.0511
All Treated
OAE04
Listing of Adverse Events Leading to Incomplete Infusions (Part 
2 NHL)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
SAC
1.0520
All Treated
OAE04
Listing of Adverse Events Leading to Infusion Interruptions (All 
Treated MM)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
SAC [A]
1.0521
All Treated
OAE04
Listing of Adverse Events Leading to Infusion Interruptions 
(Part 2 NHL)
Report for population subgroup: All 
Treated MM. Remove onset cycle 
and cycle day from all AE related 
listings.
SAC
1.0270
All Treated
OAE04
Listing of Corneal Events (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0271
All Treated
OAE04
Listing of Corneal Events (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
1.0530
All Treated
OAE04
Listing of Thrombocytopenia (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]


CONFIDENTIAL
BMA117159
219
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0531
All Treated
OAE04
Listing of Thrombocytopenia (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
1.0540
All Treated
OAE04
Listing of Hematologic Toxicity (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0541
All Treated
OAE04
Listing of Hematologic Toxicity (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
1.0550
All Treated
OAE04
Listing of Neutropenia (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0551
All Treated
OAE04
Listing of Neutropenia (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
1.0260
All Treated
OAE04
Listing of Infusion Related Reactions (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0261
All Treated
OAE04
Listing of Infusion Related Reactions (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
Hepatobiliary (Liver)
1.0410
All Treated
MH2
Listing of Medical Conditions for Subjects with Liver Stopping 
Events (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0411
All Treated
MH2
Listing of Medical Conditions for Subjects with Liver Stopping 
Events (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
1.0420
All Treated
SU2
Listing of Substance Use for Subjects with Liver Stopping 
Events (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0421
All Treated
SU2
Listing of Substance Use for Subjects with Liver Stopping 
Events (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC


CONFIDENTIAL
BMA117159
220
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
All Laboratory
1.0330
All Treated
OLB7
Listing of All Laboratory Data for Subjects with Any Value of 
Potential Clinical Importance (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0331
All Treated
OLB7
Listing of All Laboratory Data for Subjects with Any Value of 
Potential Clinical Importance (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
1.0320
All Treated
OLB13
Listing of Laboratory Data with Character Results (All Treated 
MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0321
All Treated
OLB13
Listing of Laboratory Data with Character Results (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
1.0350
All Treated
UR2A
Listing of Urinalysis Data for Subjects with Any Value of 
Potential Clinical Importance (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
1.0351
All Treated
UR2A
Listing of Urinalysis Data for Subjects with Any Value of 
Potential Clinical Importance (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
ECOG Performance Status
1.0430
All Treated
PS5A
Listing of ECOG Performance Status (All Treated MM)
Report for sub-population: Part 2 
NHL.
SAC [A]
1.0431
All Treated
PS5A
Listing of ECOG Performance Status (Part 2 NHL)
Report for sub-population: All 
Treated MM.
SAC
Response
1.0560
All Treated
RE5
Listing of Investigator-Assessed Responses (All Treated MM)
Report for sub-population: All 
Treated MM. List investigator 
reported response by visit.
SAC [A]


CONFIDENTIAL
BMA117159
221
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0561
All Treated
RE5
Listing of Investigator-Assessed Responses (Part 2 NHL)
Report for sub-population: Part 2 
NHL.List investigator reported 
response by visit.
SAC
Time-to-Event Endpoints
1.0440
All Treated
TTE9
Listing of Progression-Free Survival (All Treated MM)
Report for sub-population: All 
Treated MM. Keep all optional 
columns. Use 'First Dose Date' in 
place of 'Randomization Date'. 
Example for endpoint description: 
Censor: Last adequate asmt, 
Event: Died, etc. Use months as 
unit.
SAC [A]
1.0570
All Treated
TTE9
Listing of Duration of Response (All Treated MM) 
Report for sub-population: All 
Treated MM. Keep all optional 
columns. Use 'First Dose Date' in 
place of 'Randomization Date'. 
Example for endpoint description: 
Censor: Last adequate asmt, 
Event: Died, etc. Use months as 
unit.
SAC [A]


CONFIDENTIAL
BMA117159
222
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0580
All Treated
TTE9
Listing of Overall Survival (All Treated MM) 
Report for sub-population: All 
Treated MM. Keep all optional 
columns. Use 'First Dose Date' in 
place of 'Randomization Date'. 
Example for endpoint description: 
Censor: Last adequate asmt, 
Event: Died, etc. If all patients can 
be reconsented.
SAC [A]
1.0590
All Treated
TTE9
Listing of Time to Progression (All Treated MM) 
Report for sub-population: All 
Treated MM. Keep all optional 
columns. Use 'First Dose Date' in 
place of 'Randomization Date'. 
Example for endpoint description: 
Censor: Last adequate asmt, 
Event: Died, etc. Use months as 
unit.
SAC [A]
1.0600
All Treated
TTE9
Listing of Time to Response (All Treated MM) 
Report for sub-population: All 
Treated MM. Keep all optional 
columns. Use 'First Dose Date' in 
place of 'Randomization Date'. 
Example for endpoint description: 
Censor: Last adequate asmt, 
Event: Died, etc. Use months as 
unit.
SAC [A]


CONFIDENTIAL
BMA117159
223
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0610
All Treated
TTE9
Listing of Time to Best Response (All Treated MM) 
Report for sub-population: All 
Treated MM. Keep all optional 
columns. Use 'First Dose Date' in 
place of 'Randomization Date'. 
Example for endpoint description: 
Censor: Last adequate asmt, 
Event: Died, etc. Use months as 
unit.
SAC [A]
Death
1.0390
All Treated
DTH3
Listing of Deaths (All Treated MM)
Report for sub-population: All 
Treated MM. include the time from 
last dose in the listing and Number 
of Cycles/Last Dose (optional 
columns in DTH3). 
SAC [A]
1.0391
All Treated
DTH3
Listing of Deaths (Part 2 NHL)
Report for sub-population: Part 2 
NHL. include the time from last 
dose in the listing and Number of 
Cycles/Last Dose (optional 
columns in DTH3).
SAC
PK
1.0630
PK
PK07
Listing of Plasma GSK2857916 (ADC) Pharmacokinetic 
Concentration-Time Data 
SAC
1.0640
PK
PK07
Listing of Plasma GSK2857916 (Total Antibody) 
Pharmacokinetic Concentration-Time Data 
SAC
1.0650
PK
PK07
Listing of Plasma GSK2857916 (Unbound Antibody) 
Pharmacokinetic Concentration-Time Data 
SAC


CONFIDENTIAL
BMA117159
224
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0660
PK
PK07
Listing of Plasma cys-mcMMAF Pharmacokinetic 
Concentration-Time Data (MM)
SAC [A]
1.0661
PK
PK07
Listing of Plasma cys-mcMMAF Pharmacokinetic 
Concentration-Time Data (NHL)
SAC
1.0670
PK
PK13
Listing of Plasma GSK2857916 (ADC) PK Parameters Data 
(Untransformed) (MM)
SAC [A]
1.0671
PK
PK13
Listing of Plasma GSK2857916 (ADC) PK Parameters Data 
(Untransformed) (NHL)
SAC
1.0680
PK
PK13
Listing of Plasma GSK2857916 (Total Antibody) PK 
Parameters Data (Untransformed) (MM)
SAC [A]
1.0681
PK
PK13
Listing of Plasma GSK2857916 (Total Antibody) PK 
Parameters Data (Untransformed) (NHL)
SAC
1.0690
PK
PK13
Listing of Plasma GSK2857916 (Unbound Antibody) PK 
Parameters Data (Untransformed) (MM)
SAC [A]
1.0691
PK
PK13
Listing of Plasma GSK2857916 (Unbound Antibody) PK 
Parameters Data (Untransformed) (NHL)
SAC
1.0700
PK
PK13
Listing of Plasma cys-mcMMAF PK Parameters Data 
(Untransformed) (MM)
SAC [A]
1.0701
PK
PK13
Listing of Plasma cys-mcMMAF PK Parameters Data 
(Untransformed) (NHL)
SAC
1.0710
PK
PK15
Listing of Derived GSK2857916 (ADC) PK Parameters Cmax 
and Ctough Accumulation Ratio (MM)
SAC [A]
1.0711
PK
PK15
Listing of Derived GSK2857916 (ADC) PK Parameters Cmax 
and Ctough Accumulation Ratio (NHL)
SAC


CONFIDENTIAL
BMA117159
225
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
1.0720
PK
PK15
Listing of Derived GSK2857916 (Total Antibody) PK 
Parameters Cmax and Ctough Accumulation Ratio (MM)
SAC [A]
1.0721
PK
PK15
Listing of Derived GSK2857916 (Total Antibody) PK 
Parameters Cmax and Ctough Accumulation Ratio (NHL)
SAC
1.0730
PK
PK15
Listing of Derived GSK2857916 (Unbound Antibody) PK 
Parameters Cmax and Ctough Accumulation Ratio (MM)
SAC [A]
1.0731
PK
PK15
Listing of Derived GSK2857916 (Unbound Antibody) PK 
Parameters Cmax and Ctough Accumulation Ratio (NHL)
SAC
1.0740
PK
PK15
Listing of Derived cys-mcMMAF PK Parameters Cmax and 
Ctough Accumulation Ratio (MM)
SAC [A]
1.0741
PK
PK15
Listing of Derived cys-mcMMAF PK Parameters Cmax and 
Ctough Accumulation Ratio (NHL)
SAC
NOTES: 
A. Indicates which displays will be generated for the reporting effort for multiple myeloma


CONFIDENTIAL
BMA117159
226
16.12.14. Non-ICH Listings
Non-ICH: Listings
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Medical Conditions
30.0010
All Treated
MH2
Listing of Past Cancer-Related and Non-Cancer Related 
Medical Conditions (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0011
All Treated
MH2
Listing of Past Cancer-Related and Non-Cancer Related 
Medical Conditions (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
30.0020
All Treated
MH2
Listing of Current Cancer-Related and Non-Cancer Related 
Medical Conditions (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0021
All Treated
MH2
Listing of Current Cancer-Related and Non-Cancer Related 
Medical Conditions (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
Concomitant Medications
30.0310
All Treated
OCM1A
Listing of Prophylactic Medication for Infusion-Related 
Reactions (All Treated MM)
Report for sub-population: All 
Treated MM. Please replace the 
2nd column as ‘Drug Class/Drug 
Name’ and the last column as 
‘Reason for Medication’ 
SAC [A]
30.0311
All Treated
OCM1A
Listing of Prophylactic Medication for Infusion-Related 
Reactions (Part 2 NHL)
Report for sub-population: Part 2 
NHL. Please replace the 2nd 
column as ‘Drug Class/Drug 
Name’ and the last column as 
‘Reason for Medication’ 
SAC
30.0320
All Treated
OCM1A
Listing of Eye Medications (All Treated MM)
Report for sub-population: All 
Treated MM. Please replace the 
2nd column as ‘Drug Class/Drug 
Name’ and the last column as 
‘Reason for Medication’
SAC [A]


CONFIDENTIAL
BMA117159
227
Non-ICH: Listings
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
30.0321
All Treated
OCM1A
Listing of Eye Medications (Part 2 NHL)
Report for sub-population: Part 2 
NHL. Please replace the 2nd 
column as ‘Drug Class/Drug 
Name’ and the last column as 
‘Reason for Medication’
SAC
Blood and Blood Supportive Care Products
30.0380
All Treated
BP4
Listing of Blood Products (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0381
All Treated
BP4
Listing of Blood Products (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
30.0390
All Treated
BP5
Listing of Blood Supportive Care Products (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0391
All Treated
BP5
Listing of Blood Supportive Care Products (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
Substance Use
30.0370
All Treated
SU2
Listing of Substance Use (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0371
All Treated
SU2
Listing of Substance Use (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
Anti-Cancer Therapy, Radiotherapy and Surgical Procedures
30.0040
All Treated
AC6
Listing of Prior Anti-Cancer Therapy (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0041
All Treated
AC6
Listing of Prior Anti-Cancer Therapy (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC


CONFIDENTIAL
BMA117159
228
Non-ICH: Listings
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
30.0050
All Treated
AC7
Listing of Anti-Cancer Radiotherapy (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0051
All Treated
AC7
Listing of Anti-Cancer Radiotherapy (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
30.0060
All Treated
OSP3
Listing of Prior/On Treatment Cancer and Non-Cancer 
Related Surgical Procedures (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0061
All Treated
OSP3
Listing of Prior/On Treatment Cancer and Non-Cancer 
Related Surgical Procedures (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
30.0400
All Treated
FAC3
Listing of Follow-Up Anti-Cancer Therapy (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0401
All Treated
FAC3
Listing of Follow-Up Anti-Cancer Therapy (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
Disease Characteristics
30.0080
All Treated
DC4
Listing of Disease Characteristics at Screening (All Treated 
MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0081
All Treated
DC4
Listing of Disease Characteristics at Screening (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
30.0360
All Treated
DC3
Listing of Disease Characteristics at Initial Diagnosis (All 
Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0361
All Treated
DC3
Listing of Disease Characteristics at Initial Diagnosis (Part 2 
NHL)
Report for sub-population: Part 2 
NHL.
SAC
30.0290
All Treated
OLB7
Listing of Genetic Characteristics (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0300
All Treated
SAFE_L1
Listing of Disease Characteristics, Prior Treatment, Dose 
Modification and Response to GSK2857916 (Part 2 MM) 
Report for sub-population: Part 2 
MM. Provide a line listing by 
SAC [A]


CONFIDENTIAL
BMA117159
229
Non-ICH: Listings
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
patient with subject identifier, ISS 
stage at screening, number of 
prior lines of therapy, refractory to 
last line of therapy (Y/N), prior 
use of daratumumab (Y/N), 
refractory to both  IMID and PI 
(Y/N), Best confirmed response, 
Exposure
30.0130
All Treated
OEX9
Summary Listing of Overall Exposure and Dose Modifications 
(All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0131
All Treated
OEX9
Summary Listing of Overall Exposure and Dose Modifications 
(Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
Adverse Events
30.0540
All Treated
OAE4
Listing of Serious Adverse Events (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0541
All Treated
OAE4
Listing of Serious Adverse Events (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
30.0550
All Treated
OAE04
Listing of Drug-Related Adverse Events (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0551
All Treated
OAE04
Listing of Drug-Related Adverse Events (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
30.0560
All Treated
OAE4
Listing of Drug-Related Serious Adverse Events (All Treated 
MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0561
All Treated
OAE4
Listing of Drug-Related Serious Adverse Events (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC


CONFIDENTIAL
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230
Non-ICH: Listings
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
30.0450
All Treated
AE2
Listing of Relationship Between SOC and Verbatim Text for 
AEs Collapsed to Corneal Events 
SAC [A]
30.0460
All Treated
AE2
Listing of Relationship Between SOC and Verbatim Text for 
AEs Collapsed to Thrombocytopenia 
SAC [A]
30.0470
All Treated
AE2
Listing of Relationship Between SOC and Verbatim Text for 
AEs Collapsed to Neutrupenia 
SAC [A]
30.0480
All Treated
AE2
Listing of Relationship Between SOC and Verbatim Text for 
AEs Collapsed to Hematologic Toxicity 
SAC [A]
30.0490
All Treated
AE2
Listing of Relationship Between SOC and Verbatim Text for 
AEs Collapsed to Infusion related reactions 
SAC [A]
Deaths
30.0570
All Treated
DTH5
Listing of Subject Numbers for Specific Causes of Deaths (All 
Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0571
All Treated
DTH5
Listing of Subject Numbers for Specific Causes of Deaths 
(Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
Laboratory
30.0530
All Treated
OLB7
Listing of Grade 3 and Grade 4 Laboratory Data (All Treated 
MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0531
All Treated
OLB7
Listing of Grade 3 and Grade 4 Laboratory Data (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
30.0580
All Treated
LIVER13
Listing of Subjects Meeting Hepatobiliary Laboratory Criteria 
Post-Baseline (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0581
All Treated
LIVER13
Listing of Subjects Meeting Hepatobiliary Laboratory Criteria 
Post-Baseline (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC


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231
Non-ICH: Listings
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
30.0160
All Treated
LIVER5
Listing of Liver Monitoring/Stopping Event Reporting (All 
Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0161
All Treated
LIVER5
Listing of Liver Monitoring/Stopping Event Reporting (Part 2 
NHL)
Report for sub-population: Part 2 
NHL.
SAC
Constitutional Symptoms and Organ Examinations
30.0510
All Treated
OCS3
Listing of Constitutional Symptoms (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
30.0520
All Treated
OOE2
Listing of Organ Examinations (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
Left Ventricular Ejection Fraction
30.0500
All Treated
OLVEF2A
Listing of Left Ventricular Ejection Fraction Results (All 
Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0501
All Treated
OLVEF2A
Listing of Left Ventricular Ejection Fraction Results (Part 2 
NHL)
Report for sub-population: Part 2 
NHL.
SAC
ECG
30.0140
All Treated
OECG5A
Listing of Fridericia’s QTc Values of Potential Clinical 
Importance (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0141
All Treated
OECG5A
Listing of Fridericia’s QTc Values of Potential Clinical 
Importance (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
Vital Signs
30.0440
All Treated
OVT7A
Listing of Vital Sign Values of Potential Clinical Importance (All 
Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0441
All Treated
OVT7A
Listing of Vital Sign Values of Potential Clinical Importance 
(Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC


CONFIDENTIAL
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232
Non-ICH: Listings
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Ocular Exam
30.0260
All Treated
SAFE_L2
Listing of Visual Acuity and Abnormal Corneal Exam Results 
(All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0261
All Treated
SAFE_L2
Listing of Visual Acuity and Abnormal Corneal Exam Results 
(Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
30.0330
All Treated
SAFE_L2
Listing of Abnormal Conjunctival Exam Results (All Treated 
MM)
Report for sub-population: All 
Treated MM. Please include 
screening results and any post-
baseline abnormal results for 
each patient. Include: Centre ID/
Subj., Age(y)/ Sex/ Race, 
Reported Corneal Events (Y/N), 
Cycle/Visit, Time Since 1st Dose/ 
Time Since last Dose, Eye, Exam 
Test, Result
SAC [A]
30.0331
All Treated
SAFE_L2
Listing of Abnormal Conjunctival Exam Results (Part 2 NHL)
Report for sub-population: Part 2 
NHL. Please include screening 
results and any post-baseline 
abnormal results for each patient. 
Include: Centre ID/ Subj., Age(y)/
Sex/ Race, Reported Corneal 
Events (Y/N), Cycle/Visit, Time 
Since 1st Dose/ Time Since last 
Dose, Eye, Exam Test, Result
SAC
30.0340
All Treated
SAFE_L2
Listing of Abnormal Slit Lamp Anterior Chamber and Slit Lamp 
Lens Exam Results (All Treated MM)
Report for sub-population: All 
Treated MM. Please include 
screening results and any post-
baseline abnormal results for 
SAC [A]


CONFIDENTIAL
BMA117159
233
Non-ICH: Listings
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
each patient. Include: Centre ID/
Subj., Age(y)/ Sex/ Race, 
Reported Corneal Events (Y/N), 
Cycle/Visit, Time Since 1st Dose/ 
Time Since last Dose, Eye, Exam 
Test, Result
30.0341
All Treated
SAFE_L2
Listing of Abnormal Slit Lamp Anterior Chamber and Slit Lamp 
Lens Exam Results (Part 2 NHL)
Report for sub-population: Part 2 
NHL. Please include screening 
results and any post-baseline 
abnormal results for each patient. 
Include: Centre ID/ Subj., Age(y)/
Sex/ Race, Reported Corneal 
Events (Y/N), Cycle/Visit, Time 
Since 1st Dose/ Time Since last 
Dose, Eye, Exam Test, Result
SAC
30.0350
All Treated
SAFE_L2
Listing of Indirect Fundoscopic Exam and Intraocular Pressure 
Results (All Treated MM)
Report for sub-population: All 
Treated MM. Include: Centre ID/
Subj., Age(y)/ Sex/ Race, 
Reported Corneal Events (Y/N), 
Cycle/Visit, Time Since 1st Dose/ 
Time Since last Dose, Eye, Exam 
Test, Result
SAC [A]
30.0351
All Treated
SAFE_L2
Listing of Indirect Fundoscopic Exam and Intraocular Pressure 
Results (Part 2 NHL)
Report for sub-population: Part 2 
NHL. Include: Centre ID/ Subj., 
Age(y)/ Sex/ Race, Reported 
Corneal Events (Y/N), Cycle/Visit, 
Time Since 1st Dose/ Time Since 
last Dose, Eye, Exam Test, 
Result
SAC


CONFIDENTIAL
BMA117159
234
Non-ICH: Listings
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Health Outcomes
30.0590
All Treated
VS4
Listing of Symptom Impact and HRQoL Item Scores (All 
Treated MM)
Report for sub-population: All 
Treated MM. Use the format of 
VS4, use collected visit dates. 
List scores for Bone Pain Worst, 
Bone Pain Average, Fatigue
SAC [A]
30.0591
All Treated
VS4
Listing of Symptom Impact and HRQoL Item Scores (Part 2 
NHL)
Report for sub-population: Part 2 
NHL. Use the format of VS4, use 
collected visit dates. List scores 
for Bone Pain Worst, Bone Pain 
Average, Fatigue
SAC
30.0600
All Treated
VS4
Listing of NEI-VFQ-25 Scores (All Treated MM)
Report for sub-population: All 
Treated MM. Use the format of 
VS4, use collected visit dates. 
List overall composite score and 
11 sub-scores.
SAC [A]
30.0601
All Treated
VS4
Listing of NEI-VFQ-25 Scores (Part 2 NHL)
Report for sub-population: Part 2 
NHL. Use the format of VS4, use 
collected visit dates. List overall 
composite score and 11 sub-
scores.
SAC
30.0610
All Treated
VS4
Listing of OSDI Scores (All Treated MM)
Report for sub-population: All 
Treated MM. Use the format of 
VS4, use collected visit dates. 
List total score and 3 sub-scores.
SAC [A]


CONFIDENTIAL
BMA117159
235
Non-ICH: Listings
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
30.0611
All Treated
VS4
Listing of OSDI Scores (Part 2 NHL)
Report for sub-population: Part 2 
NHL. Use the format of VS4, use 
collected visit dates. List total 
score and 3 sub-scores.
SAC
Anti-Drug Antibody
30.0620
All Treated
SAFE_L3
Listing of Anti-GSK2857916 antibody results (All Treated MM)
Report for sub-population: All 
Treated MM.
SAC [A]
30.0621
All Treated
SAFE_L3
Listing of Anti-GSK2857916 antibody results (Part 2 NHL)
Report for sub-population: Part 2 
NHL.
SAC
PK
30.0630
PK
SAS Output of Results of Dose Proportionality Analysis Using 
Power Model 
SAC [A]
30.0640
PK
SAS Output of Results of Accumulation Ratio Assessment 
(Part 1)
SAC [A]
30.0641
PK
SAS Output of Results of Accumulation Ratio Assessment 
(Part 2 MM)
SAC [A]
30.0642
PK
SAS Output of Results of Accumulation Ratio Assessment 
(Part 2 NHL)
SAC
30.0650
PK
SAS Output of Results of Analyte Ratio Assessment at Cycle 
1 (Part 1)
SAC [A]
30.0660
PK
SAS Output of Results of Analyte Ratio Assessment at Cycle 
2 (Part 2 MM)
SAC [A]
30.0670
PK
SAS Output of Results of Analyte Ratio Assessment at Cycle
3 (Part 2 NHL)
SAC


CONFIDENTIAL
BMA117159
236
Non-ICH: Listings
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
30.0680
PK
SAS Output of Results of Analyte Ratio Assessment at Each 
Cycle (Part 1)
SAC [A]
30.0681
PK
SAS Output of Results of Analyte Ratio Assessment at Each 
Cycle (Part 2 MM)
SAC [A]
30.0682
PK
SAS Output of Results of Analyte Ratio Assessment at Each 
Cycle (Part 2 NHL)
SAC
PKPD
30.0690
PKPD
Listing of Fridericia’s QTc Change from Baseline and 
GSK2857916 (ADC) Pharmacokinetic Concentration-Time 
Data (MM)
List QTc change from baseline 
concentration for each visit
SAC [A]
30.0691
PKPD
Listing of Fridericia’s QTc Change from Baseline and 
GSK2857916 (ADC) Pharmacokinetic Concentration-Time 
Data (NHL)
List QTc change from baseline 
concentration for each visit
SAC
30.0700
PKPD
Listing of Fridericia’s QTc Change from Baseline and 
GSK2857916 (Total Antibody) Pharmacokinetic 
Concentration-Time Data (MM)
List QTc change from baseline 
concentration for each visit
SAC [A]
30.0701
PKPD
Listing of Fridericia’s QTc Change from Baseline and 
GSK2857916 (Total Antibody) Pharmacokinetic 
Concentration-Time Data (NHL)
List QTc change from baseline 
concentration for each visit
SAC
30.0710
PKPD
Listing of Fridericia’s QTc Change from Baseline and 
GSK2857916 (Unbound Antibody) Pharmacokinetic 
Concentration-Time Data (MM)
List QTc change from baseline 
concentration for each visit
SAC [A]


CONFIDENTIAL
BMA117159
237
Non-ICH: Listings
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
30.0711
PKPD
Listing of Fridericia’s QTc Change from Baseline and 
GSK2857916 (Unbound Antibody) Pharmacokinetic 
Concentration-Time Data (NHL)
List QTc change from baseline 
concentration for each visit
SAC
30.0720
PKPD
Listing of Fridericia’s QTc Change from Baseline and cys-
mcMMAF Pharmacokinetic Concentration-Time Data (MM)
List QTc change from baseline 
concentration for each visit
SAC [A]
30.0721
PKPD
Listing of Fridericia’s QTc Change from Baseline and cys-
mcMMAF Pharmacokinetic Concentration-Time Data (NHL)
List QTc change from baseline 
concentration for each visit
SAC
NOTES: 
A. Indicates which displays will be generated for the reporting effort for multiple myeloma


CONFIDENTIAL
BMA117159
238
16.13.
Appendix 13: Example Mock Shells for Data Displays
Example: POP_T1
Protocol: BMA117159                                                                             Page 1 of 1
Population: Part 1                                                           (Data as of: 30MAY2001)
Table x.xxxx
Summary of Genetic Characteristics at Screening for Multiple Myeloma Subjects (Part 1)
0.03 mg/kg
0.06 mg/kg
Total
Genetics
(N=100)
(N=100)
(N=200)
del13
5 (5%)
5 (5%)
10 (5%)
del17p13
5 (5%)
5 (5%)
10 (5%)
t(11:14)
5 (5%)
5 (5%)
10 (5%)
t(4:14)
5 (5%)
5 (5%)
10 (5%)
1q21
5 (5%)
5 (5%)
10 (5%)
Other
5 (5%)
5 (5%)
10 (5%)
Missing
5 (5%)
5 (5%)
10 (5%)
PPD


CONFIDENTIAL
BMA117159
239
Example: POP_T2
Protocol: BMA117159                                                                             Page 1 of 1
Population: Part 1                                                           (Data as of: 30MAY2001)
Table x.xxxx
Summary of Cytogenetics Risk at Screening (Part 1)
0.03 mg/kg
0.06 mg/kg
Total
Genetics
(N=100)
(N=100)
(N=200)
High Risk [1]
5 (5%)
5 (5%)
10 (5%)
Other (non-high 
risk, not done, or 
missing)
5 (5%)
5 (5%)
10 (5%)
[1] A subject is considered as high risk if the subject has any of the following cytogenetics:
t(4;14), del17p, t(14;16).
PPD


CONFIDENTIAL
BMA117159
240
Example: POP_T3
Protocol: BMA117159                                                                             Page 1 of 1
Population: Part 1                        
(Data as of: 30MAY2001)
Table x.xxxx
Summary of Prior Anti-Cancer Therapy by Drug Class of Agents for Multiple Myeloma Subjects (Part 1)
0.03 mg/kg
0.06 mg/kg
Total
Drug Class
(N=100)
(N=100)
(N=200)
Steroids
5 (5%)
5 (5%)
10 (5%)
Immunomodulator (IMID)
5 (5%)
5 (5%)
10 (5%)
LENALIDOMIDE
5 (5%)
5 (5%)
10 (5%)
POMALIDOMIDE
5 (5%)
5 (5%)
10 (5%)
THALIDOMIDE
5 (5%)
5 (5%)
10 (5%)
Proteasome Inhibitor (PI)
5 (5%)
5 (5%)
10 (5%)
BORTEZOMIB
5 (5%)
5 (5%)
10 (5%)
CARFILZOMIB
5 (5%)
5 (5%)
10 (5%)
IXAZOMIB
5 (5%)
5 (5%)
10 (5%)
Chemotherapy
5 (5%)
5 (5%)
10 (5%)
Stem Cell Transplant
5 (5%)
5 (5%)
10 (5%)
Other
5 (5%)
5 (5%)
10 (5%)
HDAC Inhibitor
5 (5%)
5 (5%)
10 (5%)
Monoclonal Antibody
5 (5%)
5 (5%)
10 (5%)
CXCR4
5 (5%)
5 (5%)
10 (5%)
DARATUMUMAB
5 (5%)
5 (5%)
10 (5%)
ELOTUZUMAB
5 (5%)
5 (5%)
10 (5%)
SILTUXIMAB
5 (5%)
5 (5%)
10 (5%)
Engineered T Cell Therapy
5 (5%)
5 (5%)
10 (5%)
  Other
5 (5%)
5 (5%)
10 (5%)
Not Classified
5 (5%)
5 (5%)
10 (5%)
PPD


CONFIDENTIAL
BMA117159
241
Example: POP_T4
Protocol: BMA117159                                                                             Page 1 of 1
Population: Part 1    
(Data as of: 30MAY2001)     
                                                           
Table x.xxxx
Summary of Multiple Myeloma Subjects Refractory to Prior Anti-Cancer Therapy by Drug Class of Agents (Part 1)
Drug Class
0.03 mg/kg
0.06 mg/kg
Total
(N=100)
(N=100)
(N=200)
Immunomodulator
5 (5%)
5 (5%)
10 (5%)
LENALIDOMIDE
5 (5%)
5 (5%)
10 (5%)
POMALIDOMIDE
5 (5%)
5 (5%)
10 (5%)
THALIDOMIDE
5 (5%)
5 (5%)
10 (5%)
Steroids
5 (5%)
5 (5%)
10 (5%)
Proteasome Inhibitor
5 (5%)
5 (5%)
10 (5%)
BORTEZOMIB
5 (5%)
5 (5%)
10 (5%)
CARFILZOMIB
5 (5%)
5 (5%)
10 (5%)
IXAZOMIB
5 (5%)
5 (5%)
10 (5%)
Chemotherapy
5 (5%)
5 (5%)
10 (5%)
Stem Cell Transplant
5 (5%)
5 (5%)
10 (5%)
Other
5 (5%)
5 (5%)
10 (5%)
Monoclonal Antibody
5 (5%)
5 (5%)
10 (5%)
CXCR4
5 (5%)
5 (5%)
10 (5%)
DARATUMUMAB
5 (5%)
5 (5%)
10 (5%)
ELOTUZUMAB
5 (5%)
5 (5%)
10 (5%)
SILTUXIMAB
5 (5%)
5 (5%)
10 (5%)
HDAC Inhibitor
5 (5%)
5 (5%)
10 (5%)
Not Classified
5 (5%)
5 (5%)
10 (5%)
Immunomodulator and Proteasome Inhibitor
5 (5%)
5 (5%)
10 (5%)
This table is summarized per subject level
PPD


CONFIDENTIAL
BMA117159
242
Example: POP_F2
Protocol: BMA117159                                                                               Page 1 of 1
Population: Part 2 MM                                                  (Data as of: 30MAY2001)
Figure x.xxxx
Plot of Dose Reduction of GSK28557916 by Cycle (Part 2 MM)
Doses 1.9 mg/kg and 1.7 mg/kg are combined and represented by 1.7 mg/kg.
PPD


CONFIDENTIAL
BMA117159
243
Example: EFF_F1
Protocol: BMA117159                                                                               Page 1 of 1
Population: Part 2 MM
   (Data as of: 30MAY2001)
PPD
PPD


CONFIDENTIAL
BMA117159
244
Example: EFF_F2
Protocol: BMA117159                                                                               Page 1 of 1
Population: Part 2 MM
   (Data as of: 30MAY2001)
Figure x.xxxx
Forest Plot - Overall Response Rate (ORR) (Part 2 MM)
PPD


CONFIDENTIAL
BMA117159
245
Example: EFF_F3
Protocol: BMA117159                                                                               Page 1 of 1
Population: Part 2 MM
   (Data as of: 30MAY2001)
Figure x.xxxx
Profile Plot of Responders (Part 2 MM)
PPD


CONFIDENTIAL
BMA117159
246
Example: SAFE_T1
Protocol: BMA117159                                                                             Page 1 of 1
Population: Part 1    
(Data as of: 30MAY2001)
Table x.xxxx
Summary of Subjects Experiencing Corneal Clinical Signs (Part 1)
0.03 mg/kg
0.06 mg/kg
Total
(N=10)
(N=20)
(N=30)
Number of Subjects Experiencing Corneal Clinical Signs 
5 (50%)
15 (75%)
20 (67%)
Corneal Epithelium Finding
Abnormal, epithelial edema
5 (50%)
12 (60%)
17 (57%)
       Abnormal, epithelial edema -subtle epithelial haze
3 (30%)
11 (55%)
14 (47%)
       Abnormal, epithelial edema - diffuse microcystic changes
2 (20%)
8 (40%)
10 (33%)
       Abnormal, epithelial edema - mild patchy microcystic changes
1 (30%)
9 (45%)
10 (33%)
       ……
Abnormal, punctate keratopathy
4 (40%)
13 (65%)
17 (57%)
       Abnormal, punctate keratopathy - mild
3 (30%)
11 (55%)
14 (47%)
       Abnormal, punctate keratopathy - moderate
3 (30%)
10 (50%)
13 (43%)
       Abnormal, punctate keratopathy - severe
2 (20%)
7 (35%)
9 (30%)
       ……
Corneal Stroma Finding
Abnormal, active
4 (40%)
13 (65%)
17 (57%)
       Abnormal, active edema - trace
3 (30%)
11 (55%)
14 (47%)
       Abnormal, active edema - 1+
3 (30%)
10 (50%)
13 (43%)
      Abnormal, active edema - 2+
2 (20%)
7 (35%)
9 (30%)
       Abnormal, active opacity - mild
1 (10%)
6 (30%)
7 (23%)
       Abnormal, active opacity - moderate
1 (10%)
5 (25%)
6 (20%)
       ……
Number of Subjects Experiencing Corneal Clinical Signs 
n
5
15
20
       Also reported corneal toxicity AE
3 (60%) 
9 (60%)
12 (60%)
       Did not report corneal toxicity AE
2 (40%)
6 (40%)
8 (60%)
PPD


CONFIDENTIAL
BMA117159
247
Example: SAFE_T2
Protocol: BMA117159                                                                             Page 1 of 1
Population: Part 1    
(Data as of: 30MAY2001)   
Table x.xxxx
Summary of Best Corrected Visual Acuity Test Scores (logMAR score)(Part 1)
0.03 mg/kg 0.06 mg/kg Total
Timepoint
Eye
BCVA Score
(N=xx)
(N=xx)
(N=xx)
Baseline
Right n
Xx
Xx
xxx
Mean
x.xx
x.xx
x.xx
SD
x.xxx
x.xxx
x.xxx
Median
x.xx
x.xx
x.xx
Min
x
x
x
Max
x
x
x
Left
n
Xx
Xx
xxx
Mean
x.xx
x.xx
x.xx
SD
x.xxx
x.xxx
x.xxx
Median
x.xx
x.xx
x.xx
Min
x
x
x
Max
x
x
x
End of study treatment
Right n
Xx
Xx
xxx
Mean
x.xx
x.xx
x.xx
SD
x.xxx
x.xxx
x.xxx
Median
x.xx
x.xx
x.xx
Min
x
x
x
Max
x
x
x
Left
n
Xx
Xx
xxx
Mean
x.xx
x.xx
x.xx
SD
x.xxx
x.xxx
x.xxx
Median
x.xx
x.xx
x.xx
Min
x
x
x
Max
x
x
x
Change from baseline to 
Right n
xx
xx
xx


CONFIDENTIAL
BMA117159
248
end of study treatment
No change/improved vision
xx (xx%)
xx (xx%)
xx (xx%)
Possible worsened vision
xx (xx%)
xx (xx%)
xx (xx%)
Definite worsened vision
xx (xx%)
xx (xx%)
xx (xx%)
Left
n
xx
xx
xx
No change/improved vision
xx (xx%)
xx (xx%)
xx (xx%)
Possible worsened vision
xx (xx%)
xx (xx%)
xx (xx%)
Definite worsened vision
xx (xx%)
xx (xx%)
xx (xx%)
Maximum (worst) change 
from baseline
Right n
xx
xx
xx
No change/improved vision
xx (xx%)
xx (xx%)
xx (xx%)
Possible worsened vision
xx (xx%)
xx (xx%)
xx (xx%)
Definite worsened vision
xx (xx%)
xx (xx%)
xx (xx%)
Left
N
xx
xx
xx
No change/improved vision
xx (xx%)
xx (xx%)
xx (xx%)
Possible worsened vision
xx (xx%)
xx (xx%)
xx (xx%)
Definite worsened vision
xx (xx%)
xx (xx%)
xx (xx%)
Note: High scores are associated with worse vision, and low scores with better vision. No change/improved 
vision is defined as a change from baseline <0.12; a possible worsened vision is defined as a change from 
baseline >=0.12 to <0.3; a definite worsened vision is defined as a change from baseline >=0.3 logMAR score. 
For “End of study Treatment”, summarize for subjects with ocular exam results at the end of study treatment; 
ocular assessment For “Change from baseline to end of study treatment”, summarize for subjects with ocular 
exam results at baseline and the end of study treatment. For “Maximum (worst) change from baseline”, summarize 
for subjects with ocular exam results at baseline and at least one post-baseline visit.
Subjects with “worse than 20/400” results will not be included in the summary.
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249
Example: SAFE_T3
Protocol: BMA117159                                                                             Page 1 of 1
Population: Part 1    
(Data as of: 30MAY2001)   
Table x.xxxx
Summary of Symptom Impact and HRQoL Item Scores Part 1)
Item Score=Bone Pain Worst
Treatment: 0.03 mg/kg (N=200)
Planned Time
n
Mean
  SD
Median
Min.
Max.
Baseline
Score
xx
xx.x
xx.xx
xx
xx
xx
Cycle 1 Day 1 to Day 8 Average Score
xx xx.x 
xx.xx xx
xx  xx 
Change from Baseline
xx xx.x 
xx.xx xx
xx  xx 
Cycle 1 Day 15    
Score
xx xx.x 
xx.xx xx
xx  xx 
Change from baseline
xx xx.x 
xx.xx xx
xx  xx 
Note: This mock up will be used for both summary of item scores and change from baseline. For summary of 
change from baseline, include baseline scores. Include Bone Pain Worst, Bone Pain Average, Fatigue worst in 
one summary table. This note dose not need to be included in the final output. Will add the notes to 
programming notes
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250
Example: SAFE_T4
Protocol: BMA117159                                                                             Page 1 of 1
Population: Part 1    
(Data as of: 30MAY2001)   
Table X.XXXX
Summary of Human Anti-GSK2857916 Antibodies (ADA) Over Time
Visit 
   Category 
Cohort 1 (x mg/kg) 
   Results 
    (N=X)
-----------------------------------------------------------------------------------------------
CYCLE 1 WEEK 1
  Screening ADA Result
    n                   X 
    POSITIVE 
      X (X%)
    NEGATIVE            X (X%) 
  Confirming ADA Result
    n 
X 
    POSITIVE            X 
    NEGATIVE            X (X%)
  
  Conclusive
    n                   X 
    NEGATIVE,CONCLUSIVE X (X%) 
Note: Negative, Conclusive is a Negative result in ADA assay (either negative screening or negative confirming 
assay result) and GSK2857916 total antibody concentration <25 ug/mL in pharmacokinetic sample collected at 
same time or same day prior to dosing as the ADA sample.
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251
Example: SAFE_T5
Protocol: BMA117159                                                                             Page 1 of 1
Population: Part 1    
(Data as of: 30MAY2001)   
Table x.xxxx
Summary of Anti-GSK2857916 Antibodies (ADA)
  X mg/kg
   (N=X)
-----------------------------------------------------------------------------------------------------------
Number of subjects with baseline ADA results  
         X (x%)
  Number of subjects with negative baseline ADA results                                      X (X%)
  Number of subjects with confirmed positive baseline ADA results 
         X (X%)
Number of subjects with post-baseline ADA results                                            X (X%)
  Number of subjects with at least one confirmed positive post-baseline ADA result           X (X%)
  
  Number of subjects with all negative post-baseline ADA results and
  at least one GSK2857916 total antibody concentration 25000 ng/mL 
   X (X%)
  Number of subjects with all negative post-baseline ADA results and 
  all GSK2857916 total antibody concentration >25000 ng/mL 
   X (X%)
  
Note a subject is considered to have a positive ADA result if they have a positive screening assay,
a positive confirmation assay and a titer value.
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252
Example: SAFE_F1
Protocol: BMA117159                                                                               Page 1 of 1
Population: Part 1            
   (Data as of: 30MAY2001)
Figure x.xxxx
Proportions of Subjects with Infusion-related Reactions (Part 1)
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253
Example: SAFE_F2
Protocol: BMA117159                                                                               Page 1 of 1
Population: All Treated MM            
   (Data as of: 30MAY2001)
Figure x.xxxx
Profile plot for patients with No Corneal Event or Grade 1 Corneal Event (Part 2 MM)
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254
Example SAFE_L1
Protocol: BMA117159                                                                             Page 1 of 1
Population: Part 2 MM                                                               (Data as of: 30MAY2003)
                                              Listing x.xxxx
     Listing of Disease Characteristics, Prior Treatment, Dose Modification and Response to GSK2857916
                                                (Part 2 MM)
Part: 2
Treatment: 3.40 MM
                                                                        Refractory
                                             Refractory                 to both
                              Number of      to Last                    IMiDs and
  Centre ID/    ISS Stage at  Prior Lines    line of      Prior         Proteasome    Best Confirmed
  Subj.         Screening     of Therapy     Therapy     Daratumumab?  Inhibitors?   Response
  --------------------------------------------------------------------------------------------------------
 
       III           6 Lines        Yes          Yes           Yes           Progressive disease
 
 
       II            7 Lines        Yes                        Yes           Very Good Partial
 
                                                                             Response (VGPR)
 
       I             8 Lines        Yes                        Yes           Very Good Partial
 
                                                                             Response (VGPR)
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255
Example SAFE_L2
Protocol: BMA117159                                                                             Page 1 of 1
Population: All Treated MM                                                           (Data as of: 30MAY2003)
Listing x.xxxx
Listing of Visual Acuity and Abnormal Corneal Exam Results
Part 1
Treatment: 0.01 mg/kg
Centre/
Subj.
Age(y)/
Sex/
Race
Experienced 
Corneal 
Clinical 
Signs / 
Reported 
Corneal 
Toxicity AE
Cycle/Visi
t
Time 
Since 1st 
Dose / 
Time 
Since 
Last Dose  Eye
Visual Acuity 
Corneal Exam Test/Result/ 
Represent a Corneal Clinical 
Sign
65/
F/
White -
White/Cauca
sian/Europe
an Heritage 
Y / Y
3 / DAY 1
43d / 1d
R
20/40
Corneal epithelium / Abnormal, 
punctate keratopathy – mild / Y
L
20/60
Corneal epithelium / Abnormal,
punctate keratopathy – mild / Y
4 / DAY 1
64d / 1d 
R
20/40
Corneal endothelium / Abnormal, 
guttata / N
L
20/40
Corneal endothelium / Abnormal, 
guttata / N
5 / DAY 1
85d / 1d 
R
20/25
Corneal epithelium / Abnormal, 
epithelial edema - mild patchy 
microcystic changes / Y
L
20/40
Corneal epithelium / Abnormal, 
epithelial edema - mild patchy 
microcystic changes / Y
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256
Example: SAFE_L3
Protocol: BMA117159                                                                               Page 1 of 1
Population: All Treated MM            
   (Data as of: 30MAY2001)
Listing x.xxxx
Listing of Anti-GSK2857916 antibody results (All Treated MM)
Treatment: X
            
                                        GSK2857916        GSK2857916
            Age (y)
                                         Concentration     Concentration
Centre ID/  Sex                     Study                Screening     Confirming            (ADC)            (Total mAb)
Subj.       Race    Visit           Date        Day      Assay         Assay        Titer    (ng/mL)           (ng/mL)
------------------------------------------------------------------------------------------------------------------------------------------
XXXX/ 
    X
   CYCLE X WEEK X  DDMMMYYYY    X        X            X            X         X                x
X           X
     X
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257
Example: PK_T1
Protocol: BMA117159                                                                               Page 1 of 1
Population: PK                         
   (Data as of: 30MAY2001)
                                                Table xx.xxx
Summary of Results of Dose Proportionality Analysis for cys-mcMMAF PK Parameters (AUC(0-inf), AUC(0-t), Cmax, 
and AUC(0- τ) Using Power Model
                                                           Standard
Parameter             Doses        Adjusted mean slope       error    DF          90% C.I.
---------------------------------------------------------------------------------------------------------
AUCIFO                0.03 mg/kg
0.98                 0.036      17        (0.92, 1.05)
(ng*hr/mL)
0.06 mg/kg
0.97
0.034
   17
     (0.93, 1.06)
………
AUCLST                0.03 mg/kg 
0.99                 0.037      17        (0.92, 1.05)
(ng*hr/mL)
0.06 mg/kg 
0.99                 0.037      17        (0.92, 1.05)
………
CMAX                  0.03 mg/kg 
0.92                 0.057      17       (0.82, 1.01)
(ng/mL)
0.06 mg/kg 
0.92                 0.057      17        (0.82, 1.01)
…………
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258
Example: PK_T2
Protocol: BMA117159                                                                               Page 1 of 1
Population: PK                         
   (Data as of: 30MAY2001)
                                                 Table x.xxxx
       Summary of Results of Accumulation Ratio Assessment for ADC Cmax on Day 1 of Cycle 2, 3, 5 vs Cmax 
on Day 1 of Cycle 1 by Dose
     ……………
Footnote: Cmax is defined as the EOI concentration at each cycle.
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259
Example: PK_F1
Protocol: BMA117159                                                                               Page 1 of 1
Population: PK                         
   (Data as of: 30MAY2001)
Figure x.xxxx


CONFIDENTIAL
BMA117159
260
Example: PK_F2
Protocol: BMA117159                                                                               Page 1 of 1
Population: PK                         
   (Data as of: 30MAY2001)
Figure x.xxxx
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Prot_000.pdf: 
2012N155299_05
CONFIDENTIAL
The GlaxoSmithKline group of companies
BMA117159
1
TITLE PAGE
Division: Worldwide Development
Information Type: Protocol Amendment
Title:
DREAMM-1: A Phase I Open-label, Dose Escalation Study to 
Investigate the Safety, Pharmacokinetics, Pharmacodynamics, 
Immunogenicity and Clinical Activity of the Antibody Drug 
Conjugate GSK2857916 in Subjects with Relapsed/Refractory 
Multiple Myeloma and Other Advanced Hematologic 
Malignancies Expressing BCMA
Compound Number:
GSK2857916
Development Phase:
PHASE I
Effective Date:
02-NOV-2017
Protocol Amendment Number: 5
Author (s):
Clinical Research Group, R&D Oncology, UP, US
Value Evidence Outcomes, UP, US
Bioanal, Immunogenicity, & Biomarkers, IVIVT, PTS, UM, US
CPSSO, UP, US
Oncology Clinical Statistics, UP, US
Oncology Clinical Statistics, UP, US
Clinical Research Group, R&D Oncology, UP, US
R&D Oncology, UP, US
Clinical Pharmacol Modeling & Simulation, Stockley Park, UK
Genetics, Stevenage, UK
Global Clinical Safety and Pharmacovigilance, UP, US
Safety, Ware, UK
Copyright 2017 the GlaxoSmithKline group of companies.  All rights reserved.  
Unauthorised copying or use of this information is prohibited.
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2012N155299_05
CONFIDENTIAL
The GlaxoSmithKline group of companies
BMA117159
2
Revision Chronology
GlaxoSmithKline
Document Number
Date
Version
2012N155299_00
2013-DEC-26
Original
2012N155299_01
2014-MAR-01
Amendment No. 1
Country specific Amendment for the United Kingdom to address required changes per 
MHRA.  Updated Exclusion Criteria to exclude subjects with current corneal disease or 
history of corneal disease.  Updated QTc withdrawal criterion to modify QTc withdrawal 
for QTc >500msec and to include > 60 msec increase from baseline.  Updated Data 
Management Section 12 to include details on dissemination of data and communication 
plan.  
2012N155299_02
2014-MAR-20
Amendment No. 2
Global Amendment to address required changes per the FDA.  Updated Inclusion Criteria 
with minimum weight requirement.  Updated Blood Volumes.  Revised Time and Events 
Tables. Corrected typographical errors.
2012N155299_03
2014-MAY-05
Amendment No. 3
Country specific Amendment for Canada to address required changes per Health Canada.  
Updated preparation instructions of GSK2857916.
2012N155299_04
2016-MAY-05
Amendment No. 4
Global Amendment to include patient reported outcome instruments in the Part 2 multiple 
myeloma cohort and refine the lymphoma histologies eligible in Part 2 BCMA-
expressing lymphoma cohort. Additionally, the requirement for 60% of tumor cells 
staining positive for BCMA expression was removed. The total number of subjects that 
may be enrolled is presented by a range of 80 to 95 to provide an updated estimate based 
on the number of subjects who enrolled at the time of the amendment.  Additional 
modifications include: changing the time-point specific blood specimens are collected for 
baseline/pre-treatment immunogenicity and biomarker measurements, and the visit 
window for certain assessments.
2012N155299_05
2017-NOV-02
Amendment No. 5
Global amendment to include additional follow up of multiple myeloma subjects for 
ocular exams (for those whose corneal signs or symptoms have not resolved), additional 
patient reported outcome instruments, addition of time-to-event endpoints as exploratory 
objectives. Subjects who have completed treatment or the 3 month follow up visit (end of 
study) prior to amendment 5 will be reconsented for further follow up and survival status. 
Other administrative changes are also included


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2012N155299_05
CONFIDENTIAL
BMA117159
4
SPONSOR/MEDICAL MONITOR INFORMATION PAGE
Medical Monitor and Sponsor Contact Information:
Role
Name
Day Time 
Phone 
Number
After-hours 
Phone/Cell/
Pager 
Number
GSK Address
Primary 
Medical 
Monitor
 
 
MD
GlaxoSmithKline
1250 South Collegeville Road
Mailstop UP-4300
Collegeville, PA 19426, USA
Secondary 
Medical 
Monitor
 
 MD, 
PhD
GlaxoSmithKline
1250 South Collegeville Road
Mailstop UP4300
Collegeville, PA 19436, USA
Sponsor Registered Address:
GlaxoSmithKline
Iron Bridge Road
Stockley Park West, Uxbridge, Middlesex, UB11
1BU, UK
Telephone:  
GlaxoSmithKline
Five Moore Drive 
P.O. 13398
Research Triangle Park, NC 27709-3398, USA
Telephone: 
GlaxoSmithKline
1250 South Collegeville Road
Collegeville, PA 19426, USA
Telephone Number:
In some countries, the clinical trial sponsor may be the local GlaxoSmithKline affiliate 
company (or designee).  Where applicable, the details of the Sponsor and contact person 
will be provided to the relevant regulatory authority as part of the clinical trial 
submission.
Regulatory Agency Identifying Number(s):
Compound Number
IND Number
EudraCT Number
GSK2857916
119333
2013-004549-18
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2012N155299_05
CONFIDENTIAL
BMA117159
5
INVESTIGATOR PROTOCOL AGREEMENT PAGE
For protocol number BMA117159
I confirm agreement to conduct the study in compliance with the protocol, as amended by 
this protocol amendment.
I acknowledge that I am responsible for overall study conduct. I agree to personally 
conduct or supervise the described study.
I agree to ensure that all associates, colleagues and employees assisting in the conduct of 
the study are informed about their obligations. Mechanisms are in place to ensure that site 
staff receives the appropriate information throughout the study. 
Investigator Name:
Investigator Address:
Investigator Phone Number:
Investigator Signature
Date


2012N155299_05
CONFIDENTIAL
BMA117159
6
TABLE OF CONTENTS
PAGE
LIST OF ABBREVIATIONS...........................................................................................12
PROTOCOL SYNOPSIS...............................................................................................16
1.
INTRODUCTION....................................................................................................32
1.1.
Background ................................................................................................32
1.2.
GSK2857916..............................................................................................33
1.2.1.
Background .................................................................................33
1.2.2.
Preclinical Pharmacology.............................................................33
1.2.3.
Preclinical Pharmacokinetics and Metabolism of 
GSK2857916...............................................................................35
1.2.3.1.
Single dose pharmacokinetics ....................................35
1.2.3.2.
Repeat dose pharmacokinetics...................................35
1.2.3.3.
Distribution, Metabolism, and Excretion......................37
1.2.3.4.
Pharmacokinetic drug interactions..............................37
1.2.3.4.1.
Victim interaction potential......................37
1.2.3.4.2.
Perpetrator interaction potential..............38
1.2.4.
Toxicology of GSK2857916 (anti-BCMA MMAF)..........................38
1.2.5.
Repeat dose toxicity ....................................................................38
1.2.5.1.
Rat .............................................................................38
1.2.5.2.
Cynomolgus monkey..................................................40
1.2.6.
Genotoxicity.................................................................................43
1.2.6.1.
Route assessment for genotoxic impurities ................43
1.2.7.
Local tolerance ............................................................................43
1.3.
Benefit:Risk Assessment ............................................................................44
1.3.1.
Risk Assessment .........................................................................44
1.3.2.
Benefit Assessment.....................................................................46
1.3.3.
Overall Benefit:Risk Conclusion...................................................46
2.
OBJECTIVE(S), ENDPOINT(S) AND HYPOTHESIS .............................................46
3.
INVESTIGATIONAL PLAN.....................................................................................49
3.1.
Discussion of Study Design ........................................................................49
3.2.
Study Schematic.........................................................................................51
3.3.
Part 1: Dose-Escalation Phase ...................................................................51
3.3.1.
Dose Escalation on Schedule 1 (GSK2857916 
administered once every three weeks; 21 days = 1 cycle) ...........52
3.3.1.1.
Single Subject Cohort Run-in (Schedule 1 only).........52
3.3.1.2.
Description of N-CRM for Schedule 1.........................54
3.3.1.2.1.
Planned Dose Levels..............................54
3.3.1.2.2.
Implementation of N-CRM ......................55
3.3.1.2.3.
Bayesian Prior ........................................56
3.3.2.
Dose Escalation on Schedule 2 (GSK2857916 
administered once weekly x3, 1 week rest; 28 days = 1 
cycle)...........................................................................................57
3.3.3.
Dose-Limiting Toxicity - Part 1 only..............................................58
3.3.4.
Maximum Tolerated Dose............................................................59
3.4.
RP2 Dose and Administration Schedule Selection for Part 2 ......................59


2012N155299_05
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BMA117159
7
3.5.
Intra-Subject Dose Escalation.....................................................................61
3.6.
Rationale ....................................................................................................61
3.6.1.
Rationale for Study ......................................................................61
3.6.2.
Rationale for Population...............................................................61
3.6.3.
Rationale for Starting Dose..........................................................62
3.6.3.1.
Human PK prediction..................................................62
3.6.3.2.
Starting dose determination........................................64
3.6.3.3.
Potential therapeutic dose determination....................67
3.6.4.
Rationale for Endpoints................................................................68
3.7.
Study Treatment .........................................................................................68
3.7.1.
Treatment Assignment.................................................................68
3.8.
Dosage and Administration of Study Treatment(s)......................................69
3.8.1.
Blinding........................................................................................69
3.9.
Safety Management Guidelines..................................................................69
3.9.1.
Liver Chemistry Stopping Criteria ................................................69
3.9.1.1.
Liver Chemistry Follow-up Procedures .......................69
3.9.2.
QTc Stopping Criteria ..................................................................71
3.9.3.
Troponin Evaluation and Stopping Criteria...................................72
3.9.4.
Left Ventricular Ejection Fraction (LVEF) .....................................72
3.9.4.1.
LVEF Stopping Criteria...............................................72
3.9.4.2.
Valvular Toxicity Stopping Criteria..............................73
3.9.5.
Infusion-related Reactions and Cytokine Release 
Syndrome ....................................................................................74
3.9.6.
Allergic and Anaphylactic reaction ...............................................75
3.9.7.
Tumor Lysis Syndrome (TLS) Prevention and Treatment 
Recommendations.......................................................................75
3.9.8.
Ocular Toxicity and Stopping Criteria...........................................76
3.10.
Guidelines for Events of Special Interest and Dose Modifications...............76
3.10.1.
Guidelines for Events of Special Interest .....................................76
3.10.2.
Predicted Toxicities and Proposed Dose 
Adjustments/Stopping Criteria......................................................77
3.10.3.
Dose Modifications ......................................................................82
4.
INVESTIGATIONAL PRODUCT(S) ........................................................................83
4.1.
Description of Investigational Product.........................................................83
4.2.
Preparation/Handling/Storage of GSK2857916 Investigational 
Product.......................................................................................................83
4.3.
Product Accountability ................................................................................84
4.4.
Treatment Compliance................................................................................85
4.5.
Treatment of Investigational Product Overdose ..........................................85
5.
STUDY POPULATION...........................................................................................85
5.1.
Number of Subjects ....................................................................................85
5.2.
Subject Selection Criteria............................................................................86
5.2.1.
Inclusion Criteria..........................................................................86
5.2.2.
Exclusion Criteria.........................................................................89
6.
COMPLETION OR WITHDRAWAL OF SUBJECTS...............................................90
6.1.
Screen and Baseline Failures .....................................................................90
6.2.
Subject Completion Criteria ........................................................................91
6.3.
Permanent Discontinuation from Study Treatment......................................91
6.4.
Subject Withdrawal.....................................................................................92


2012N155299_05
CONFIDENTIAL
BMA117159
8
6.5.
Study Completion .......................................................................................92
6.6.
Treatment after the End of Study................................................................92
7.
STUDY ASSESSMENTS AND PROCEDURES .....................................................92
7.1.
Time and Events Tables .............................................................................93
7.1.1.
Dose Escalation...........................................................................94
7.1.1.1.
Every 3 Weeks Dosing Schedule for Multiple 
Myeloma.....................................................................94
7.1.1.2.
Weekly Dosing Schedule (Dose Escalation) for 
Multiple Myeloma .......................................................97
7.1.2.
Dose Expansion.........................................................................102
7.1.2.1.
Every 3 Weeks Dosing Schedule for Multiple 
Myeloma...................................................................102
7.1.2.2.
Dose Expansion Weekly Dosing Schedule for 
Multiple Myeloma .....................................................107
7.1.2.3.
Dose Expansion Every 3 Weeks Dosing 
Schedule for Lymphomas.........................................111
7.1.2.4.
Dose Expansion Weekly Dosing Schedule for 
Lymphomas..............................................................115
7.2.
Demographic/Medical History and Baseline Assessments........................118
7.2.1.
Critical Baseline Assessments...................................................118
7.3.
Safety Evaluations....................................................................................118
7.3.1.
Physical Examinations...............................................................119
7.3.2.
ECOG Performance Status........................................................119
7.3.3.
Vital Signs..................................................................................119
7.3.4.
Electrocardiogram......................................................................119
7.3.5.
Echocardiogram.........................................................................120
7.3.6.
Ocular Exam..............................................................................120
7.3.7.
Laboratory Assessments ...........................................................120
7.3.8.
Pregnancy Testing and Reporting..............................................122
7.3.9.
Immunogenicity..........................................................................122
7.3.10.
Visual Functioning Questionnaires.............................................122
7.3.10.1.
National Eye Institute Visual Functioning 
Questionnaire-25......................................................123
7.3.10.2.
Ocular Surface Disease Index Questionnaire ...........123
7.4.
Pharmacokinetics .....................................................................................123
7.4.1.
Blood Sample Collection for Pharmacokinetics..........................123
7.4.2.
Urine Sample Collection for Pharmacokinetics ..........................124
7.4.3.
Pharmacokinetic Sample Analysis .............................................124
7.5.
Translational Research.............................................................................124
7.5.1.
Pharmacodynamics ...................................................................124
7.5.1.1.
BCMA Receptor Occupancy in bone marrow 
plasma cells..............................................................125
7.5.1.2.
sBCMA Analysis.......................................................125
7.5.1.3.
Activated TBNK cells................................................125
7.5.1.4.
Cytokine and Chemokine Analysis ...........................125
7.5.2.
Subject stratification/predictive biomarkers ................................125
7.5.3.
Tumor Biomarker Analysis.........................................................126
7.5.3.1.
Circulating cell free DNA (cfDNA) analysis ...............126
7.6.
Genetics ...................................................................................................127
7.7.
Evaluation of Anti-Cancer Activity .............................................................127
7.8.
Health Outcomes: Quality of Life ..............................................................128


2012N155299_05
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BMA117159
9
7.8.1.
Bone Pain/Fatigue Assessment (eDiary) ...................................128
7.8.2.
Exit Interview and Follow-up Interview.......................................129
8.
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS...................................129
8.1.
Definition of an AE....................................................................................129
8.2.
Definition of an SAE..................................................................................130
8.2.1.
Sentinel Events..........................................................................131
8.3.
Laboratory and Other Safety Assessment Abnormalities Reported 
as AEs and SAEs .....................................................................................132
8.3.1.
Cardiovascular Events...............................................................132
8.4.
Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as SAEs...................................................................................133
8.5.
Time Period and Frequency of Detecting AEs and SAEs..........................133
8.5.1.
Method of Detecting AEs and SAEs...........................................133
8.5.2.
Prompt Reporting of SAEs and Other Events to GSK ................134
8.5.3.
Regulatory reporting requirements for SAEs..............................135
9.
LIVER CHEMISTRY FOLLOW-UP PROCEDURES.............................................135
9.1.
Liver Chemistry Testing Procedures .........................................................135
9.2.
Liver Chemistry Monitoring Criteria...........................................................136
9.3.
Drug Restart/Rechallenge Following Liver Events that are Possibly 
Related to Study Drug...............................................................................136
9.4.
Drug Restart Following Transient, Resolving Liver Events Not 
Related to Study Drug...............................................................................137
10. CONCOMITANT MEDICATIONS AND NON-DRUG THERAPIES .......................138
10.1.
Permitted Medication(s)............................................................................138
10.2.
Prohibited Medication(s) ...........................................................................138
10.3.
Permitted Non-Drug Therapies .................................................................138
10.4.
Prohibited Non-Drug Therapies ................................................................138
11. LIFESTYLE AND/OR DIETARY RESTRICTIONS................................................139
11.1.
Contraception ...........................................................................................139
11.1.1.
Female Subjects........................................................................139
11.1.2.
Male Subjects............................................................................140
11.2.
Lactation Restrictions................................................................................140
12. DATA MANAGEMENT .........................................................................................140
12.1.
Data Dissemination and Communication Plan ..........................................141
13. DATA ANALYSIS AND STATISTICAL CONSIDERATIONS.................................142
13.1.
Hypothesis(es)..........................................................................................142
13.1.1.
Part 1: Dose-Escalation Phase ..................................................142
13.1.2.
Part 2: Expansion Cohort...........................................................142
13.2.
Sample Size Determination ......................................................................142
13.2.1.
Part 1: Dose-Escalation Phase ..................................................142
13.2.2.
Part 2: Expansion Cohort...........................................................143
13.3.
Sample Size Sensitivity.............................................................................144
13.3.1.
Sample Size Re-estimation........................................................144
13.4.
Data Analysis Considerations ...................................................................144
13.4.1.
Analysis Populations..................................................................144
13.5.
Treatment Comparisons ...........................................................................145


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13.5.1.
Primary Comparisons of Interest................................................145
13.5.1.1.
Primary Comparison of Interest ................................145
13.5.2.
Other Comparisons of Interest...................................................145
13.6.
Interim Analysis ........................................................................................147
13.6.1.
Part 1.........................................................................................147
13.6.2.
Part 2.........................................................................................147
13.7.
Key Elements of Analysis Plan .................................................................149
13.7.1.
Anti-Cancer Activity Analyses ....................................................149
13.7.2.
Safety Analyses.........................................................................150
13.7.2.1.
Extent of Exposure ...................................................150
13.7.2.2.
Adverse Events ........................................................150
13.7.2.3.
Clinical Laboratory Evaluations ................................150
13.7.2.4.
Immunogenicity Analyses.........................................151
13.7.2.5.
Other Safety Measures.............................................151
13.7.3.
Pharmacokinetic Analyses.........................................................152
13.7.3.1.
Raw Plasma Concentrations ....................................152
13.7.3.2.
Statistical Analysis of Pharmacokinetic Data ............153
13.7.4.
Pharmacokinetic/Pharmacodynamic Analyses...........................154
13.7.4.1.
Translational Research Analyses .............................154
13.7.4.2.
Novel Biomarker(s) Analyses ...................................154
13.7.5.
Genetic Analyses.......................................................................154
13.7.6.
Pharmacodynamic Biomarkers and Exploratory Response 
Prediction Biomarkers................................................................154
13.7.6.1.
Exploratory analyses of DNA, and Protein................155
13.7.7.
Clinical Activity Analyses ...........................................................155
13.7.8.
Health Outcome Analyses .........................................................156
14. STUDY CONDUCT CONSIDERATIONS .............................................................157
14.1.
Posting of Information on Clinicaltrials.gov................................................157
14.2.
Regulatory and Ethical Considerations, Including the Informed 
Consent Process ......................................................................................157
14.3.
Urgent Safety Measures ...........................................................................157
14.4.
Quality Control (Study Monitoring) ............................................................157
14.5.
Quality Assurance.....................................................................................158
14.6.
Study and Site Closure .............................................................................158
14.7.
Records Retention....................................................................................159
14.8.
Provision of Study Results to Investigators, Posting of Information 
on Publicly Available Clinical Trials Registers and Publication..................159
15. REFERENCES.....................................................................................................160
16. APPENDICES......................................................................................................163
16.1.
Appendix 1: International Myeloma Working Group Uniform
Response Criteria for Multiple Myeloma ...................................................163
16.2.
Appendix 2: Revised Response Criteria for Malignant Lymphoma............166
16.3.
Appendix 4: NYHA Functional Classification System ................................168
16.4.
Appendix 5: Modified Diet in Renal Disease Formula................................169
16.5.
Appendix 6: ECOG Performance Status1 .................................................170
16.6.
Appendix 7: Genetics................................................................................171
16.7.
Appendix 8: Liver Safety Drug Restart Guidelines ....................................174
16.8.
Appendix 9: Urine Protein Creatinine (UPC) Ratio Clinical meaning 
of UPC......................................................................................................178


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16.9.
Appendix 10: Blood Requirements............................................................179
16.9.1.
Blood Requirements for All Lab Tests, Except PK .....................179
16.9.1.1.
Dose Escalation: Every 3 Weeks for Multiple 
Myeloma...................................................................179
16.9.1.2.
Dose Escalation:  Weekly for Multiple Myeloma .......179
16.9.1.3.
Dose Expansion:  Every 3 Weeks for Multiple 
Myeloma...................................................................180
16.9.1.4.
Dose Expansion:  Weekly for Multiple Myeloma .......181
16.9.1.5.
Dose Expansion:  Every 3 Weeks for 
Lymphomas..............................................................181
16.9.1.6.
Dose Expansion:  Weekly for Lymphomas ...............182
16.9.2.
Blood Requirements for PK .......................................................182
16.9.3.
Total Blood Requirements .........................................................183
16.10. Appendix 11:  Pgp Inhibitors .....................................................................184
16.11. Appendix 12: Protocol Amendment Changes............................................185
16.11.1. Amendment 1 ............................................................................185
16.11.2. Amendment 2 ............................................................................192
16.11.3. Amendment 3 ............................................................................231
16.11.4. Amendment 4 ............................................................................232
16.11.5. Amendment 5 ............................................................................253


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LIST OF ABBREVIATIONS
ABC
Airway breathing and circulation
ADA
Anti-drug antibody
ADC
Antibody drug conjugate
ADCC
Antibody dependent cellular cytotoxicity
AE
Adverse event
ALP
Alkaline phosphatase
ALT
Alanine aminotransferase
APRIL
A proliferation-inducing ligand
AST
Aspartate aminotransferase
AUC
Area under the concentration-time curve
AUC (0-∞)
Area under the concentration-time curve to infinity
AUC (0-)
Area under the concentration time curve over the dosing 
interval
AV
Atrioventricular
BAFF/BLyS
B-cell activating factor/B-lymphocyte stimulator
BAL
Bronchoaveolar lavage
BCMA
B cell maturation antigen
BCRP
Breast cancer resistant protein
BCVA
Best corrected visual acuity
BED
Biologically Effective Dose
BNP
B-type natriuretic peptide
BSA
Body surface area
BWT
Body weight
CBC
Complete blood count
CBR
Clinical benefit rate
CDISC
Clinical Data Interchange Standards Consortium
cfDNA
Cell-free deoxyribonucleic acid
CI
Confidence interval
CK
Creatine kinase
CK-MB
Creatine kinase MB-isoenzyme
CL
Clearance
CLL
Chronic lymphocytic leukemia
Cmax
Maximum plasma drug concentration
CPMS
Clinical Pharmacology Modeling and Simulation
CPR
Cardio-pulmonary resuscitation
CR
Complete response
CRM
Continual Reassessment Method
CRP
C-reactive protein
CT
Computer tomography
cTn
Cardiac troponin
Ctrough
Trough plasma concentration
CYP
Cytochrome P450
CV%
Coefficient of variation percent 
Cys-mcMMAF
cys Monomethyl auristatin F 


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DIC
Disseminated intravascular coagulation
DOR
Duration of response
DLBCL
Diffuse large B-cell lymphoma
DLT
Dose limiting toxicity
DMPK
Drug metabolism and pharmacokinetics
DNA
Deoxyribonucleic acid
EC50
Concentration associated with 50% maximal effect
ECL
Electrochemiluminescence
ECOG
Eastern Cooperative Oncology Group
eCRF
Electronic case report form
eDiary
Electronic Diary
EM
Extramedullary
EOI
End of infusion
FACTS
Fixed and adapted clinical trials simulator
FLC
Free light chain
FSH
Follicle stimulating hormone
FTIH
First time in human
GLDH
Glutamate dehydrogenase
GLP
Good laboratory practice
GSK
GlaxoSmithKline
GSK2857914
GlaxoSmithKline anti-BCMA antibody (CA8 J6M0 
Potelligent)
GSK2857916
GlaxoSmithKline anti-BCMA antibody drug conjugate (CA8 
J6M0 Potelligent MMAF)
HBs-Ag
Hepatitis B surface antigen
HBc
Hepatitis B core
HBV
Hepatitis B
HCV
Hepatitis C
HNSTD
Highest non-severely toxic dose
HPLC
High performance liquid chromatography
HRT
Hormone replacement therapy
IC50
Concentration associated with 50%  inhibition of maximal 
effect 
IDSL
Integrated Data Standards Library
Ig
Immunoglobulin
IHC
Immunohistochemistry
IMIDs
Immunomodulators
IMWG
International Myeloma Working Group
INR
International normalized ratio
IP
Intraperitoneal
IV
Intravenous
IVRS
Integrated voice response system
KIM-1
Kidney injury molecule-1
LBCL
Large B-cell lymphoma
LDH
Lactate dehydrogenase
MABEL
Minimum anticipated biological effect level


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mc
Maleimidocaproyl
MDRD
Modified diet in renal disease
MI
Myocardial infarction
MM
Multiple Myeloma
MMAF
Monomethyl auristatin F
MR
Minimal response
MRI
Magnetic resonance Imaging
MTD
Maximum Tolerated Dose
NAG
N-Acetyl-β-D-glucosaminase
NCI-CTCAE
National Cancer Institute – Common Terminology Criteria 
for Adverse Events
N-CRM
A modification of the Continual Reassessment Method 
(CRM) proposed by Neuenschwander et al.
NEI-VFQ-25
National Eye Institute Visual Functioning Questionnaire - 25
NF-B
Nuclear factor kappa light-chain enhancer of activated B 
cells
NK
Natural killer
NONMEM
Non linear mixed effects modelling
OAT
Organic anion transporter
OATP
Organic anion transporter polypeptide
ORR
Overall response rate
OSDI
Ocular Surface Disease Index
PBMC
Peripheral blood mononuclear cells
PCR
Polymerase chain reaction
PD
Pharmacodynamic
PET
Probability of early termination
PFS
Progression-free survival
PFT
Pulmonary function test
Pgp
P-glycoprotein
PK
Pharmacokinetic(s)
PR
Partial response
PRO
Patient reported outcome
PT
Prothrombin time
PTS
Platform technologies and sciences
PTT
Partial thromboplastin time
QID
4 times a day
QoL
Quality of life
RAP
Reporting and analysis plan
RAMOS
Registration and medication ordering system
REML
Restricted maximum likelihood
RIBA
Recombinant immunoblot assay
RNA
Ribonucleic acid
Ro
Observed accumulation ratio
RO
Receptor occupancy
RPA-1
Renal papillary antigen-1
RP2
Recommended Phase 2 


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SAE
Serious adverse event
sBCMA
Soluble B-cell maturation antigen
sCR
Stringent complete response
SD
Stable disease
SOI
Start of infusion
SPEP
Serum protein electrophoresis
SPM
Study procedure manual
SPR
Surface plasmon resonance
t½ 
Half-life
TBNK
T-cell, B-cell and Natural Killer cells
Tlast
Time of last quantifiable concentration
TLS
Tumor lysis syndrome
Tmax
Time to maximum drug concentration
TTP
Time to progression
ULN
Upper limit of normal
UPEP
Urine protein electrophoresis
VGPR
Very good partial response
Vd
Volume of distribution
Vss
Volume of distribution at steady state
WM
Waldenstrom’s macroglobulinemia
Trademark Information
Trademarks of the GlaxoSmithKline 
group of companies
Trademarks not owned by the 
GlaxoSmithKline group of companies
NONE
FACTS
SAS
WinNonlin


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PROTOCOL SYNOPSIS
TITLE
A Phase I Open-label, Dose Escalation Study to Investigate the 
Safety, Pharmacokinetics, Pharmacodynamics, 
Immunogenicity and Clinical Activity of the Antibody Drug 
Conjugate GSK2857916 in Subjects with Relapsed/Refractory 
Multiple Myeloma and  Other Advanced  Hematologic 
Malignancies Expressing BCMA
PROTOCOL NUMBER
BMA117159
CLINICAL PHASE
I
COMPOUND(S)
GSK2857916
STUDY RATIONALE
This is a FTIH study that will assess the safety, 
pharmacokinetics (PK), pharmacodynamics (PD) and 
therapeutic potential of GSK2857916 in multiple myeloma 
(MM) and lymphomas that express BCMA. GSK2857916 is a 
humanized immunoglobulin (IgG1) antibody drug conjugate 
(ADC) which binds specifically to B cell maturation antigen 
(BCMA). The parent anti-BCMA antibody (J6M0) is 
conjugated to the microtubule inhibitor monomethyl auristatin-
F (MMAF) via a protease resistant maleimidocaproyl (mc) 
linker to produce the GSK2857916 ADC molecule.  Upon 
binding to the cell surface, GSK2857916 is rapidly internalized 
and active drug (cys-mcMMAF) is released inside the cell.
GSK2857916 has been produced in an afucosylated form to 
generate an enhanced antibody dependent cellular cytotoxicity
(ADCC) response upon binding to FcRIIIa receptors on the 
surface of human effector cells. This dual mechanism of action 
may improve efficacy by targeting dividing through ADC and 
non-dividing tumor cells through ADCC. Importantly, BCMA 
expression is maintained at the cell surface over time following 
GSK2857916 binding and internalization due to rapid BCMA 
receptor recycling and/or new protein synthesis.  GSK2857916 
has demonstrated dose-dependent cytotoxic activity in 
myeloma cell lines, ex vivo primary myeloma tumor samples, 
as well as preclinical myeloma mouse tumor models.  
GSK2857916 has also shown activity in B cell lymphoma cell 
lines that express BCMA.
The hypothesis is that GSK2857916 can be safely administered 
to subjects with BCMA positive malignancies at doses where 
target engagement can be demonstrated.  This study will 
determine if adequate target engagement of BCMA receptors 
translates into clinical benefit for subjects with MM and 


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BCMA positive lymphomas. 
STUDY OBJECTIVES, 
ENDPOINTS AND 
HYPOTHESES
Hypothesis:  GSK2857916 can be safely administered to 
subjects with MM and with BCMA positive lymphomas at 
doses where target engagement can be demonstrated.
Objective
Endpoint
Primary

To determine safety, 
tolerability, maximum 
tolerated dose (MTD), 
and recommended phase 
(RP2) dose and schedule 
of GSK2857916 
administered

Adverse events (AE) and 
changes in clinical signs 
and laboratory 
parameters 
Secondary 

To evaluate the 
pharmacokinetic (PK) 
profile of GSK2857916 
and the breakdown 
product cys-mcMMAF) 
after intravenous (IV) 
single and repeat dose 
administration in subjects 
with relapsed/refractory 
MM and BCMA 
expressing lymphomas

GSK2857916 and cys-
mcMMAF PK 
parameters following IV 
single and repeat dose 
administration during 
dose escalation as data 
permit (e.g., AUCs 
Cmax, tmax, CL, VSS, t½ 
[single dose], Cmax and 
Ctrough [repeat dose]).
GSK2857916 population 
PK parameters in 
expansion cohorts at the 
RP2 dose (e.g. clearance 
(CL), volume of 
distribution (Vd), and 
relevant covariates 
which may influence 
exposure (e.g. age, 
weight, or disease-
related covariates e.g. 
BCMA expression) 

To assess anti-drug 
antibody (ADA)
formation after IV single 
and repeat dose 
administration of 
GSK2857916

ADA incidence and 
titers after single and 
repeat IV dosing of 
GSK2857916


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
To explore the initial 
anti-tumor activity of 
GSK2857916 in subjects 
with relapsed/refractory 
MM and BCMA 
expressing lymphomas

Clinical activity 
measured as Overall 
Response Rate (ORR) 
which is defined as 
follows:
o
For MM: the 
percentage of 
subjects 
achieving 
confirmed partial 
response or better 
(PR) 
o
In addition, the 
percentage of 
subjects with 
minimal response 
(MR) will be 
assessed for 
clinical benefit 
rate (CBR) 
(Appendix 1)
o
For Lymphomas: 
the percentage of 
subjects 
achieving PR or 
better (PR) 
(Appendix 2)
Exploratory 

To evaluate PD markers 
in MM after treatment 
with GSK2857916

sBCMA levels, BCMA 
receptor occupancy and 
cell death markers in 
subjects with MM. 

To explore relationships 
of GSK2857916 plasma 
concentrations/exposure 
with pharmacodynamics 
(PD), safety and clinical 
activity 

Relationship between 
receptor occupancy, 
tumor cell death 
markers, sBCMA and 
GSK2857916 plasma 
PK parameters;

Relationship between 
safety/clinical activity 
(e.g. ORR) and 
GSK2857916  PK 
parameters 


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
To characterize the 
relationship between 
clinical response and 
other biologic tumor 
characteristics (DNA, 
protein analysis)

BCMA expression levels 
on malignant cells as 
measured by IHC and/or 
flow cytometry in tumor 
tissue, serum sBCMA 
levels and their 
relationship to clinical 
response

To investigate the 
relationship between 
genetic variants in the 
host and response to 
study medicine, or 
susceptibility, severity 
and progression of
disease

Relationship between 
host genetic variation 
and response to study 
medicine or 
susceptibility, severity 
and progression of 
disease

To explore the effect of 
GSK2857916 on 
symptoms (including 
bone pain, fatigue and 
visual symptoms) and 
impacts on HRQoL in 
subjects with 
relapsed/refractory MM
(Part 2)

Changes from baseline 
in bone pain/fatigue and 
analgesic use as 
measured by the eDiary

Interviews with subjects 
to further characterize 
changes in symptoms
(including bone pain, 
fatigue and visual 
symptoms) and impacts 
on HRQoL

To explore changes in 
visual symptoms and 
function following 
discontinuation of 
treatment with 
GSK2857916

Changes in visual 
symptoms and impacts 
as measured by the 
OSDI and NEI-VFQ-25 
following treatment 
discontinuation

Follow-up telephone 
interviews conducted to 
further understand 
subjects experience with 
visual symptoms and 
changes in symptoms 
and related impacts 
following treatment 
discontinuation 


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
To explore the initial 
anti-tumor activity of 
GSK2857916 in subjects 
with relapsed/refractory 
MM in terms of time-to-
event (TTE) endpoints 
(Part 2 MM)

Time to progression 
(TTP), defined as: the 
time from first dose until 
the earliest date of PD 
per International 
Multiple Myeloma 
Working Group
(IMWG), or death due to 
PD.

Duration of response 
(DOR), defined as: the 
time from first 
documented evidence of 
PR or better; until the 
time when disease 
progression (PD) is 
documented per IMWG; 
or death due to PD 
occurs in participants 
who achieve a response, 
i.e. confirmed PR or 
better.

Time to response (TTR), 
defined as: the time 
between the date of first 
dose and the first 
documented evidence of 
response (PR or better).

Progression-free 
survival (PFS), defined 
as: the time from first 
dose until the earliest 
date of disease 
progression (PD) per
IMWG, or death due to 
any cause.

Number of deaths
STUDY DESIGN
This study is an open-label, dose escalation Phase I FTIH study 
to determine the RP2 dosing regimen of GSK2857916.  The 
recommended dose and schedule will be selected based on the 
safety, pharmacokinetic (PK), and pharmacodynamic (PD) 
profiles observed after administering the study drug to subjects 
with multiple myeloma (MM).  The study will consist of two 
parts and will enroll approximately 80-95 subjects.  The Part 1 
dose escalation phase will characterize the safety and 


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tolerability of respective dosing regimen for GSK2857916 
utilizing the model based on the Neuenschwander continual 
reassessment method (N-CRM).  Initially, GSK2857916 will 
be administered via 60 min intravenous (IV) infusion once 
every three weeks (21 days = 1 cycle). After a MTD or 
recommended phase 2 dose (RP2D) has been established on 
the once every three weeks schedule, the safety, tolerability, 
and PK of once-weekly dosing of GSK2857916 for three 
consecutive weeks with 1 week rest (28 days = 1 cycle) may be 
explored in an additional cohort(s). Part 2 will explore the 
safety, tolerability, PK, PD, and clinical activity of the RP2
dose of GSK2857916 identified in Part 1.  Subjects with MM 
(n=40), and lymphomas expressing BCMA (n=10) will be 
enrolled in expansion cohort in Part 2. Futility analyses will be 
performed on the MM cohort after approximately 15, 22, 30 
subjects have been enrolled. Sparse PK sampling will be 
collected to further characterize GSK2857916 exposures for 
the selected dose schedule.  Although not required for MM, 
subjects with lymphomas will be enrolled in Part 2 based upon 
the detection of positive BCMA staining of tumor cells in a 
prospective immunohistochemistry screening assay performed 
at a central laboratory.
NUMBER OF SUBJECTS
Approximately 80-95 subjects will be enrolled.
Up to 30 subjects with relapsed/refractory MM will be enrolled 
in Part 1, Schedule 1; Schedule 2, if explored, will enroll up to 
15 additional subjects in Part 1.
Up to 40 subjects with relapsed/refractory MM and up to 10 
subjects with lymphomas expressing BCMA will be enrolled in 
Part 2.
INCLUSION/EXCLUSION 
CRITERIA
Inclusion Criteria:
1.
Provide signed written informed consent, which includes 
compliance with the requirements and restrictions listed 
in the consent form.
2.
Male or female, 18 years or older (at the time consent is 
obtained)
3.
Eastern Cooperative Oncology Group (ECOG) 
performance status of 0 or 1 (Appendix 6)
4.
Part 1/dose escalation:

Histologically or cytologically confirmed diagnosis 
of: Multiple Myeloma in a subject who fulfills all 
of the following: 


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
has undergone stem cell transplant, or is considered 
transplant ineligible, 

has been pretreated with at least the 3 following 
classes of anti-myeloma drugs: alkylators, 
proteasome inhibitors and immunomodulators, 

has demonstrated progression on, or within 60 days 
of completion of the last therapy. 
Part 2 /MM cohort:

Histologically or cytologically confirmed diagnosis 
of: Multiple Myeloma in a subject who fulfills all 
of the following: 

has undergone stem cell transplant, or is considered 
transplant ineligible, 

has been pretreated with at least the 3 following 
classes of anti-myeloma drugs: alkylators, 
proteasome inhibitors and immunomodulators, 

and has demonstrated progression on, or within 60 
days of completion of the last therapy. 
AND has measurable disease with at least one of the 
following:
a. Serum M-protein 0.5 g/dL (5 g/L)
b. Urine M-protein  ≥200 mg/24h
c. Serum FLC assay: Involved FLC level ≥5 
mg/dL (≥50 mg/L) and an abnormal serum free 
light chain ratio (<0.26 or >1.65)
d. Biopsy proven plasmacytoma (should be 
measured within 28 days of Screening Visit)
or
Part 2/BCMA positive Lymphoma cohort: 
a.
Subject with one of the following 
lymphomas: Diffuse Large B-cell 
Lymphoma (DLBCL) or follicular 
lymphoma (FL) that exhibits positive 
BCMA expression on tumor cells as 
determined by a central laboratory using a 
validated IHC assay. Eligible subjects with 
BCMA positive lymphomas must also 
fulfill the prior treatment requirements as 
follows:
b. DLBCL: at least 2 prior lines of systemic 


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therapy containing at least one line of 
chemo-immunotherapy with anti-CD20 
antibody, and either has undergone stem 
cell transplant or is considered transplant 
ineligible
c.
FL: at least 2 prior lines of systemic therapy 
5.
Subjects 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
c.
subject meets the remainder of the eligibility 
criteria outlined in this protocol
6.
Adequate organ system functions as defined in 
Table below:
System
Laboratory Values
Hematologic
Absolute neutrophil count (ANC)1
1.0 X 109/L
Hemoglobin
8.0 g/dL
Platelets
50 X 109/L
Coagulation
INR 
1.5 
PTT
1.5 x ULN
Hepatic
Total bilirubin
≤1.5 X ULN (isolated 
bilirubin >1.5xULN is 
acceptable if bilirubin 
is fractionated and 
direct bilirubin <35%)
AST and ALT
1.5 X ULN
Renal
Serum creatinine or
Calculated creatinine clearance2
Albuminuria 
<1.2XULN
≥ 60 mL/min for Part 
1;
50 mL/min for Part 
2 if data supports 
loosening criteria
500mg/24hr
Cardiac
LVEF (Echo)
Troponin 
50%
1xULN


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1.
Without Growth factor support for the past 14 days, excluding erythropoietin
2.
As calculated by Modified Diet in Renal Disease (MDRD) formula  
(Appendix 5)
NOTE:  Laboratory results obtained during Screening should 
be used to determine eligibility criteria.  In situations where 
laboratory results are outside the permitted range, the 
investigator may opt to retest the subject and the subsequent 
within range screening result may be used to confirm 
eligibility.
7.
A female subject is eligible to participate if she is of:

Non-childbearing potential (i.e. physiologically 
incapable of becoming pregnant) defined as pre-
menopausal females with a documented tubal ligation 
or hysterectomy; or postmenopausal defined as 12 
months of spontaneous amenorrhea [in questionable 
cases a blood sample with simultaneous follicle 
stimulating hormone (FSH) > 40 MIU/mL and estradiol 
< 40 pg/mL (<147 pmol/L) is confirmatory].  Females 
on hormone replacement therapy (HRT) and whose 
menopausal status is in doubt will be required to use 
one of the contraception methods specified if they wish 
to continue their HRT during the study.  Otherwise, 
they must discontinue HRT to allow confirmation of 
post-menopausal status prior to study enrollment.  For 
most forms of HRT, at least 2-4 weeks will elapse 
between the cessation of therapy and the blood draw; 
this interval depends on the type and dosage of HRT.  
Following confirmation of their post-menopausal 
status, they can resume use of HRT during the study 
without use of a contraceptive method.

Women of childbearing potential must have a negative 
serum pregnancy test within 72 hours of first dose of 
study treatment and agree to use effective 
contraception, as defined in Section 11.1.1, during the 
study and for 60 days following the last dose of study 
treatment.
8.
Men with a female partner of childbearing potential must 
have either had a prior vasectomy or agree to use 
effective contraception as described in Section 11.1.2
from the time of first dose of study until 60 days after 
the last dose of study treatment to allow for clearance of 
any altered sperm.
9.
All prior treatment-related toxicities (defined by 
National Cancer Institute- Common Toxicity Criteria for 
Adverse Events (NCI-CTCAE), version 4) must be 


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≤Grade 1 at the time of enrollment except for alopecia, 
and grade 2 neuropathy.
Exclusion Criteria:
1.
Systemic anti-tumor therapy within 14 days, or 
plasmapheresis within 7 days prior to the first dose of 
study drug.
2.
Use of an investigational drug within 14 days or five 
half-lives, whichever is shorter, preceding the first dose 
of study drug.  Prior treatment with a monoclonal 
antibody within 30 days of receiving the first dose of 
study drug. 
3.
History of an allogeneic stem cell transplant.  Subjects 
with a history of an autologous stem cell transplant are 
NOT excluded if they meet Inclusion Criterion #5. 
4.
Presence of active renal condition (infection, 
requirement for dialysis or any other condition that 
could affect subject’s safety). Subjects with isolated 
proteinuria resulting from MM are eligible, provided 
they fulfil criteria given in Table 14.
5.
Evidence of active mucosal or internal bleeding.
6.
Any major surgery within the last four weeks.
7.
Any serious and/or unstable pre-existing medical, 
psychiatric disorder or other conditions (including lab 
abnormalities) that could interfere with subject’s safety, 
obtaining informed consent or compliance to the study 
procedures. 
8.
Known active infection requiring antibiotic treatment.
9.
Evidence of severe or uncontrolled systemic diseases 
(e.g., unstable or uncompensated respiratory, hepatic, 
renal or cardiac disease)
10. Subjects with previous or concurrent malignancies are 
allowed only if the second tumor is not contributing to 
the subject’s illness.  The subject must not be receiving 
active therapy, other than hormonal therapy for this 
disease and the disease must be considered medically 
stable for at least 2 years.
11. Evidence of cardiovascular risk including any of the 
following:
a.QTc interval ≥ 470 msecs.
b. Evidence of current clinically significant 


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uncontrolled arrhythmias;
i. including clinically significant ECG 
abnormalities including 2nd degree 
(Type II) or 3rd degree atrioventricular 
(AV) block.
c.History of myocardial infarction, acute coronary 
syndromes (including unstable angina), 
coronary angioplasty, or stenting or bypass 
grafting within six months of Screening.
d. Class III or IV heart failure as defined by the 
New York Heart Association functional 
classification system (Appendix 4)
e.Uncontrolled hypertension
f.Subjects with intra-cardiac defibrillators or 
permanent pacemakers;
g. Abnormal cardiac valve morphology 
(≥Grade 2) documented by echocardiogram 
(subjects with grade 1 abnormalities [i.e., mild 
regurgitation/stenosis] can be entered on 
study).  Subjects with moderate valvular 
thickening should not be entered on study.
12. Known immediate or delayed hypersensitivity reaction or 
idiosyncrasy to drugs chemically related to GSK2857916 
or any of the components of the study treatment.
13. Pregnant or lactating female.
14. Known HIV infection.
15. Subjects with positive test for Hepatitis B surface (HBS-
Ag) or Hepatitis B core (HBc)antigen  
16. Subjects with positive test for hepatitis C (HCV) infection 
are excluded regardless of viral load.  If hepatitis C 
antibody test is positive, a confirmatory polymerase chain 
reaction (PCR) or recombinant immunoblot assay (RIBA)
test should be performed.  If the PCR or RIBA test is
negative, subject is eligible for this trial.
17. Current active liver or biliary disease (with the exception of 
Gilbert's syndrome or asymptomatic gallstones, liver 
metastases or otherwise stable chronic liver disease per 
investigator’s assessment).
18. Current corneal disease or a history of corneal disease. 


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STUDY TREATMENT 
DOSE/ROUTE/REGIMEN
Product name :
GSK2857916 Solution, 20 
mg/mL, 1.5mL anti-BCMA-ADC 
Formulation 
description:
Solution containing 20mg/mL 
GSK2857916
Dosage form :
Supplied as frozen liquid.  
Recommended storage condition 
is -50C to -15C. 
Unit dose 
strength(s)/Dose 
Level(s):
20mg/mL, 1.5mL (Refer to Section 
3.3.1.2.1 for dose levels)
Physical Description:
GSK2857916 Solution for Infusion 
is clear or opalescent; colorless, 
yellow to brown liquid 
Route/
Administration/ 
Duration:
Delivered as IV solution (see 
Section 3.8)
Dosing instructions:
Dilute GSK2857916 solution in 
normal 0.9% saline to the 
appropriate concentration for the 
dose.  See Section 4.2 for 
compatible administration 
materials.  Doses of GSK2857916 
are to be administered as an IV 
infusion via an infusion pump that 
can ensure precision to the 
decimal point of a mL for the 
infusion rate at lower doses. It is 
recommended to prime the tubing 
with at least 15 mL prior to dosing.
Manufacturer/ Source 
of Procurement:
GSK
Manufacturer Lot 
number
132373860
SAFETY 
ASSESSMENTS
Measurements to evaluate safety will include height, weight, heart 
rate (HR), blood pressure (BP), temperature, echocardiogram, 
troponin I, 12-lead ECG, clinical chemistry, hematology, and other 
laboratory tests listed in Table 15 standard disease assessments 
for MM including bone marrow aspirate (cytology and flow 


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cytometry) and M protein analysis, ECOG performance status, 
and complete physical examination. AEs and laboratory results will 
be graded according to the NCI-CTCAE v4.0 [NCI, 2009]. Planned 
time points for all safety assessments are listed in the Time and 
Events Tables (Section 7.1).
PHARMACOKINETIC/ 
PHARMACODYNAMIC 
ASSESSMENT(S)
In Part 1 on Schedule 1 (i.e., GSK2857916 administered once 
every 21 days) PK samples will be taken in all subjects for 
both GSK2587916 and cys-mcMMAF measurement according 
to the Time and Events Tables in Section 7.1
In Part 1 on Schedule 2 (i.e., GSK2857916 administered once 
weekly for 3 consecutive weeks, 1 week rest) PK samples will 
be taken in all subjects for both GSK2857916 and cys-
mcMMAF measurement according to the Time and Events 
Tables in Section 7.1. 
In the Part 2 dose expansion phase in subjects with MM PK 
samples will be taken for both GSK2587916 and cys-
mcMMAF measurement according to the Time and Events 
Tables in Section 7.1. 
In the Part 2 dose expansion phase in subjects with BCMA 
positive lymphomas PK samples will be taken for both 
GSK2587916 and cys-mcMMAF measurement according to 
the Time and Events Tables in Section 7.1. 
Pharmacodynamic markers will be collected according to the 
schedule outlined in the Time and Events Tables in Section 
7.1.
Samples for immunogenicity assessment will be collected as 
outlined in the Time and Events Tables in Section 7.1.
CLINICAL ACTIVITY 
ASSESSMENT
Clinical activity will be measured as Overall Response Rate 
(ORR) which is defined as follows:
For MM: the percentage of subjects with confirmed stringent 
complete response (sCR), complete response (CR), very good 
partial response (VGPR), and partial response (PR) as assessed 
by 2011 recommendation of the International Myeloma 
Working Group (IMWG) Panel I.   Clinical benefit rate (CBR), 
including minimal response (MR), may be considered in 
addition to ORR (Appendix 1).  
For Lymphomas: the percentage of subjects with confirmed 
CR, PR, as described in the Revised Response Criteria for 
Malignant Lymphoma (Appendix 2)


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TRANSLATIONAL 
RESEARCH
Pharmacodynamic assessments will include evaluation of 
tumor tissue by flow cytometry and immunohistochemistry 
(IHC) for plasma cell expression of free BCMA receptors and 
GSK2857916 bound receptors, cell cycle markers, as well as 
apoptosis markers on tumor cells, to understand anti-tumor 
responses. IHC markers may include but will not be limited to 
BCMA, Blimp1, CD38, CD45, cys-mcMMAF, CC3, PH3, and 
MPM-2.  Additionally, tumor tissue may be evaluated for any 
DNA /RNA changes correlating with response.  Serum levels 
of free and GSK2857916 bound sBCMA will be assessed by 
Meso-Scale Discovery immunoassay and correlated with 
clinical outcome to treatment with GSK2857916.  Cytokines
and chemokines will be measured; cell-free deoxyribonucleic 
acid (cfDNA) may be measured.  
Leukocyte population will be characterized and may be 
correlated with clinical outcome.
A genetics samples will be collected in Part 2 and may be used 
to investigate variability in response that may be attributable to 
host genetic variation, if it emerges during this clinical study or 
a series of clinical studies of GSK2857916 (Appendix 7).
Further, the genetic sample may be used to investigate the 
relationship between genetic variation and disease 
(susceptibility, severity or progression).
PATIENT REPORTED 
OUTCOMES
Part 2/MM cohort: changes in symptoms and health-related 
quality of life (HRQoL) will be assessed with the use of the 
Bone Pain/Fatigue diary.
Changes in visual symptoms and impacts with the use of the 
OSDI and NEI-VFQ-25


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STATISTICAL 
METHODS
Part1: After each dosing cohort, the N-CRM will be used to 
recommend the next dose level based on observed dose-
limiting toxicities (DLTs).  The dose escalation decisions will 
be based on this recommendation as well as the totality of the 
safety, pharmacokinetic, and pharmacodynamic data.
Part 2: Futility analyses will be performed on the MM cohort 
after approximately 15, 22, and 30 evaluable subjects have 
been enrolled. The methodology utilized is based on the 
predictive probability of success if enrollment continues to 40 
subjects [Lee, 2008].
Clinical Activity
The exact 95% confidence interval (CI) for overall response 
rate (ORR) and clinical benefit rate (CBR) will be provided. 
Subjects with unknown or missing response will be treated as 
non-responders, i.e., these subjects will be included in the 
denominator when calculating percentages of response.
For the Part 2 MM population, additional exploratory time-to-
event (TTE) endpoint will include TTP, DOR, TTR, and PFS, 
as data permits. For all the TTE endpoints listed above, median 
TTE with 95% CI will be estimated employing the Kaplan-
Meier method as data permits. A Kaplan-Meier survival curve 
will be generated. The number and percentage of subjects who 
had the event or were censored will also be reported.
Adverse Events: Adverse events will be summarized by 
frequency and proportion of total participants, by system organ 
class and preferred term. Separate summaries will be given for 
all AEs, treatment-related AEs, SAEs, and AEs leading to 
discontinuation of study treatment.
The incidence of deaths and the primary cause of death will be 
summarized.
Clinical Laboratory Evaluation: The evaluation of clinical 
laboratory tests will focus on selected laboratory analytes from 
the hematology and blood chemistry panel.
Descriptive statistics (mean, standard deviation, median, range) 
will be used to summarize observed laboratory values and 
change from baseline in observed value at each scheduled visit 
or worst-case post baseline, as appropriate.
The worst-case- toxicity grade in hematology and chemistry 
result during the treatment will be summarized. Shift tables 
from baseline to the worst toxicity grade during treatment will 


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be provided for each laboratory analyte.
Other Safety Measures: Data for vital signs, 
electrocardiograms (ECGs), and echocardiograms (ECHOs) 
will be summarized. For continuous variables, these summaries 
will include sample size, mean, median, standard deviation, 
minimum, and maximum.  For categorical variables, the 
summaries will include frequencies and corresponding 
percentages.  


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1.
INTRODUCTION
1.1.
Background
Multiple myeloma (MM) accounts for 1% of all cancers and for 10% of all hematologic 
malignancies.  Approximately 20,000 people will be diagnosed with MM each year in the 
United States [Rajkumar, 2011a]. The median age at diagnosis is approximately 70 years.  
Newly diagnosed patients less than 60 years of age have a 30% probability for 10-year 
survival [Palumbo, 2011].  Recent progress in understanding the biology of the disease 
has resulted in significant improvements in treatment strategies for MM.  Drugs that are 
currently approved for MM fall into three separate classes of agents:  alkylating agents 
(melphalan, cyclophosphamide), proteasome inhibitors (bortezomib, carfilzomib), and 
immunomodulators (IMIDs: thalidomide, lenalidomide, pomalidomide).  These highly 
active agents used in combination are providing tangible benefits for patients with MM 
[Rajkumar, 2011b].  Importantly, improvements in survival outcomes have been noted in 
patients with MM and current treatment strategies provide a very good chance for 
response in the first line. Unfortunately, duration of response and response rates decline 
dramatically in each subsequent line of treatment for this malignancy. MM remains 
incurable and the need for new treatment modalities is well recognized. 
The normal function of B cell maturation antigen (BCMA) is to promote cell survival by 
transduction of signals from two known ligands (BAFF/BLyS and 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].  
BCMA is expressed in various B-cell malignancies, including MM.  The expression 
levels in MM vary from patient to patient, but our studies demonstrate that all patients 
tested express detectable levels of BCMA protein on their tumor cells. BCMA expression 
varies between MM patients and GlaxoSmithKline (GSK) studies have shown that in 
samples taken from MM patients (N=45), 31% have low expression, 38% moderate 
expression and 31% high expression of BCMA as detected by immunohistochemistry 
(IHC).  BCMA was also analyzed by flow cytometry in tumor cells from 48 MM patients 
which aligned well with IHC results. In addition, other B-cell malignancies including 
Follicular Lymphoma (FL) [Basso, 2005; GSKin-house data], Diffuse Large B-Cell 
Lymphoma (DLBCL), Large B-Cell Lymphoma (LBCL), Chronic Lymphocytic 
Leukemia (CLL) and Waldenstrom’s Macroglobulinemia (WM) [Montes-Moreno, 2012] 
[Elsawa, 2006] [Endo, 2007] were reported to express BCMA at varying frequencies; 
DLBCL and FL were among the B-cell hematologic malignancies exhibiting the highest 
frequency of BCMA expression.
A soluble form of BCMA has also been reported [Sanchez, 2012].  Higher amounts of 
this soluble form were found in supernatants isolated from cultures of MM-containing 
peripheral blood and bone marrow mononuclear cells compared to normal cells.  
Moreover, soluble BCMA (sBCMA) was higher in the sera of MM patients (n=209) 
compared to sera from age-matched, healthy controls (n=40; P < 0.0001).  Measurement 
of serum levels of BCMA was conducted by immunoassay to confirm the prevalence and 
level of sBCMA expression in MM.  Soluble BCMA is present in serum at a median 


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concentration of 9.28 ng/mL (range 6.10-14.09 ng/mL) in healthy volunteers (N=38) and 
is elevated in the serum of MM patients (N = 44) to median of 148.64 ng/mL (range 2.40-
1062.48 ng/mL). 
The restricted normal tissue expression profile of BCMA, along with its upregulation and 
survival function in MM and other BCMA-positive cancers makes it an attractive target 
for a therapeutic antibody with direct cell killing activity. 
1.2.
GSK2857916
1.2.1.
Background
GSK2857916 is a humanized IgG1 antibody drug conjugate (ADC) which binds 
specifically to BCMA. The parent anti-BCMA antibody (J6M0) is conjugated to the 
microtubule inhibitor monomethyl auristatin-F (MMAF) via a protease resistant 
maleimidocaproyl (mc) linker to produce the GSK2857916 ADC molecule.  Upon 
binding to the cell surface, GSK2857916 is rapidly internalized and active drug (cys-
mcMMAF) is released inside the cell. 
GSK2857916 has been produced in an afucosylated form to generate an enhanced 
antibody dependent cellular cytotoxicity (ADCC) response upon binding to FcRIIIa 
receptors on the surface of human effector cells. The rationale for this dual mechanism of 
action is to improve efficacy by targeting dividing and non-dividing tumor cells. 
Importantly, BCMA expression is maintained at the cell surface over time following 
GSK2857916 binding and internalization due to rapid BCMA receptor recycling and/or 
new protein synthesis.  GSK2857916 has demonstrated dose-dependent cytotoxic activity 
in myeloma cell lines, ex vivo primary myeloma tumor samples, as well as preclinical 
myeloma mouse tumor models.
1.2.2.
Preclinical Pharmacology
J6M0, the parent antibody for GSK2857916 binds specifically to human BCMA with an 
affinity of 1.61 nM as defined by surface plasmon resonance (SPR), and the binding 
properties were maintained following drug conjugation. J6M0 competes for binding to 
BCMA with both known ligands BAFF/BlyS and APRIL, and inhibits ligand-induced 
NF-ĸB signalling with an IC50 of 0.91 g/mL and 2.43 µg/mL, respectively. However, in 
cell proliferation assays, GSK2857916 failed to inhibit cell growth directly.
A total of 16 cell lines were used to demonstrate the antitumor activity of GSK2857916 
via the ADC mechanism in BCMA expressing cells and to investigate the relationship 
between BCMA expression and potency. The IC50 of GSK2857916 was determined for 
each cell line tested (Table 1). In general, the highest BCMA expressing cell lines (NCI-
H929, MM.1R and JJN3) were most sensitive to GSK2857916 and the lowest expressing 
cell lines (ARH-77, MC/CAR and HuNS1) were least sensitive. In the 4 negative control 
cell lines (KU812, Raji, HUT78 and MOLT-4) where no expression or only trace 
expression of BCMA was observed by flow cytometry, there was no detectable growth-
inhibitory activity at any of the concentrations tested. This demonstrates the specificity of 
GSK2857916 for BCMA expressing cells.


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Table 1
Mean IC50 Values for GSK2857916
Cell Line
IC50 (ng/mL)
95% CI
U266
3.0
1.4 to 6.5
ARH77.10B5
3.4
2.5 to 4.8
MM.1R
11.5
10.9 to 12.1
NCI-H929
13.8
13.2 to 14.3
JJN3
26.0
24.1 to 28.1
MM.1S
53.2
49.5 to 57.0
LP1
55.7
44.3 to 70.1
ARH77
72.7
58.8 to 89.7
RPMI8226
79.1
60.1 to 104.1
L363
93.7
74.3 to 118.2
OPM2
114.3
97.0 to 134.9
KMS128M
148.4
124.1 to 177.5
HUNS1
244.2
198.4 to 300.5
MC/CAR
>1000
Negative Control Cell Lines
KU812
>1000
Raji
>1000
HUT78
>1000
MOLT4
>1000
GSK2857916 also had ADCC activity when tested against a panel of MM target cell lines 
using a fresh human PBM effector cells from healthy donors. The ADCC EC50 values 
were NCI-H929 [0.57 ng/mL], RPMI-8226 [4.09 ng/mL], JJN-3 [14.42 ng/mL], OPM-2 
[4.15 ng/mL] and U266 [9.04 ng/mL], respectively.
GSK2857916 demonstrated dose dependent ADCC and ADC activity against primary 
CD138+ myeloma tumor cells from nine myeloma patients. These results demonstrate 
that GSK2857916 is capable of killing primary myeloma cells with potency similar to 
that observed in cell lines.


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Myeloma tumor models in mice were also tested to ensure that GSK2857916 has activity 
in vivo. The cell lines selected for subcutaneous xenograft studies were NCI-H929 and 
OPM2. GSK2857916 administration resulted in complete tumor regression in both 
models at 4 mg/kg dosed by intraperitoneal (IP) route twice weekly for 4 weeks. In an 
orthotopic, bone marrow dissemination mouse model using MM.1S cells, treatment with 
GSK2857916 dosed at 0.4mg/kg or 4.0 mg/kg IP 9 times over the course of 1 month 
resulted in complete reduction of tumor burden and significantly increased survival of 
mice. These results demonstrate the anti-tumor activity of GSK2857916 at achievable in 
vivo dose levels.
1.2.3.
Preclinical Pharmacokinetics and Metabolism of GSK2857916
1.2.3.1.
Single dose pharmacokinetics
The pharmacokinetics of GSK2857916 (ADC) and cys-mcMMAF has been investigated 
following IV (bolus) administration to the rat and cynomolgus monkey.  Plasma 
concentrations were quantifiable over the entire sampling period (144 hours in rat and 
504 hours in cynomolgus monkey) at doses of 10, 30 and 100 mg/kg for the rat and 3, 10, 
and 30 mg/kg for the cynomolgus monkey.  The maximum concentrations were observed 
at 0.25 hours (first sampling occasion) in the rat and between 0.25 and 6 hours in the 
cynomolgus monkey.  Systemic exposure (Cmax and AUC0-t) for ADC and total increased 
approximately proportionally with increasing dose and there was no notable sex 
difference.  Similar concentrations between ADC and total antibody suggest that 
GSK2857916 remains largely intact in circulation.  This is further confirmed with the 
relatively low levels of cys-mcMMAF observed in both plasma and urine.  GSK2857916 
was cleared slowly (total plasma clearance; rat 0.333ml/hr/kg and cynomolgus monkey 
1.07 ml/hr/kg).  The mean steady state volume of distribution (Vss) was low in both the 
rat and monkey being 97.6 mL/kg and 105 mL/kg, respectively; suggesting GSK2857916 
is mainly confined to the systemic circulation.
1.2.3.2.
Repeat dose pharmacokinetics
Rat
The pharmacokinetics of GSK2857916 and cys-mcMMAF has been investigated 
following IV infusion administration to male and female rats over 3-weeks (once weekly 
at 3, 10 or 30 mg/kg on Days 1, 8 and 15), followed by a 12-week off-dose period.
Systemic exposure (AUC0-168 and Cmax) increased proportionally with increasing dose and 
there were no notable differences in the systemic exposure between sexes.  The systemic 
exposure on Day 15 was slightly higher (up to 2.4-fold) than that on Day 1.  Tmax was 
observed at 0.25 hours, the first sampling point.
The AUC for ADC and total antibody were similar to one another at each dose level on 
Day 1 and was generally higher for total antibody on Day 15.  The Cmax was generally 
lower for total antibody than ADC on Day 1, but similar on Day 15. The average half-life 
was 11 days.


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For cys-mcMMAF, there was insufficient data available to determine AUC on Day 1 in 
the low dose group (3 mg/kg). The systemic exposure increased proportionally with 
increasing dose and there were no notable differences in systemic exposure between 
sexes.  The systemic exposure on Day 15 was higher (up to 6.4-fold) than that on Day 1.  
Tmax ranged from 0.25 to 48 hours.
There were quantifiable concentrations of cys-mcMMAF in the urine samples collected 
on Day 7, 14, 22, 43R, 64R, 85R and 106R from toxicology animals.  The mean total 
amount of cys-mcMMAF recovered in urine generally increased proportionally with 
increasing dose of GSK2857916.  Cys-mcMMAF was not quantifiable in the urine 
samples collected on Days -6, -5 and -1 (pre-treatment) at any dose or in control group 
samples.
Cynomolgus Monkey
The pharmacokinetics of GSK2857916 and cys-mcMMAF has been investigated 
following IV bolus administration to male and female cynomolgus monkeys over 3-
weeks (once weekly at 1, 3 or 10 mg/kg on Days 1, 8 and 15), followed by a 12-week off-
dose period.
Gender-averaged systemic exposure increased proportionally with increasing dose and 
there were no notable differences in the systemic exposure between sexes.  The gender-
averaged systemic exposure increased 1.2- to 2.1-fold, respectively, from Week 1 to 
Week 3.  Following IV bolus administration of GSK2857916, Tmax was observed at 0.25 
hour (the first sampling time point) in the majority of animals. 
The systemic exposures for ADC and total antibody were similar, with total antibody 
consistently being slightly higher than ADC.  The average half-life was 4 days.
For cys-mcMMAF, the gender averaged systemic exposure (AUC0-48hr) increased 
proportionally with increasing dose and there were no notable differences in systemic 
exposure between sexes. The changes in gender-averaged systemic exposure from 
Week 1 to Week 3 were less than 2-fold. Tmax was variable, although in most animals 
Tmax was achieved within 6 hours after dosing during Weeks 1 and 3.


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Table 2
Gender Averaged Pharmacokinetic Values for GSK2857916 (ADC) 
Following IV Administration to Cynomolgus Monkeys
PK Parameters
AUC0-167 
(g.h/mL)
Cmax (g/mL)
Tmax (h)
t½ (h)
Week
Dose 
(mg/Kg/week)
1
3
1
3
1
3
3
1
865
1240
22.3
27.5
0.25
0.25
N/A
3
2330
3760
58.8
63.3
0.25
0.25
96.4
10
11200
21500
249
292
0.25
0.25
N/A
1.2.3.3.
Distribution, Metabolism, and Excretion
No studies have been performed at GSK specifically to evaluate the distribution, 
metabolism and excretion of GSK2857916.
A study performed on a similar antibody linked to MMAF has been performed [Alley, 
2009] [Alley, 2010].  Distribution has shown using radio-labeled ADC that accumulation 
is rapid in the tumor with the proportion of released drug relative to conjugated drug 
increased over time in the tumor.  In most normal tissues, both the mAb and drug 
decreased over time in conjunction with the serum concentrations, except in organs 
involved in hepatobiliary clearance where there was a 4 hour peak post dose followed by 
a rapid decrease.  The difference between tumor versus normal biodistribution and 
release kinetics yielded a tumor exposure to released drug tens to hundreds of times 
higher than that of normal tissue.
Metabolism studies have shown the directly conjugated drug linker releases cys-
mcMMAF after ADC catabolism, consistent with proteolytic degradation of the mAb to 
release the drug.
Cys-mcMMAF was detected in rat urine between 7 and 106 days following IV 
administration.  However, it was not possible to make a quantitative assessment of renal 
excretion.
1.2.3.4.
Pharmacokinetic drug interactions
1.2.3.4.1.
Victim interaction potential
Victim PK interactions occur when a co-administered drug changes the PK of the
investigational agent. 


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Elimination pathways (metabolism/catabolism and/or drug transporter) for GSK2587916 
or cys-mcMMAF in humans have not been characterised. As a consequence, care should 
be exercised when GSK2857916 is co-administered with potent cytochrome P450 (CYP) 
inhibitors, CYP inducers, and transporter modulators. In vitro cys-mcMMAF was shown 
to be a substrate of P-glycoprotein (P-gp) with an efflux ratio of 31-fold in the presence 
of verapamil. As cys-mcMMAF has low permeability (<10 nm/s) changes in P-gp 
activity could potentially affect the pharmacokinetics of cys-mcMMAF in vivo. 
Concomitant dosing of GSK2857916 with strong Pgp inhibitors should be avoided unless 
considered medically necessary (See Appendix 11:  Pgp Inhibitors for list of relevant Pgp 
inhibitors).
1.2.3.4.2.
Perpetrator interaction potential
Perpetrator interactions are changes in the PK of a co-administered drug caused by the 
investigational agent. 
No clinical studies have been performed by GSK to evaluate the potential for cys-
mcMMAF or GSK2587916 to interact with substrates of cytochrome P450 or drug 
transporters P-gp, OATP, BCRP or OAT.  In vitro, Cys-mcMMAF did not appear to be a 
direct, time- or metabolism-dependent inhibitor of CYP1A2, CYP2B6, CYP2C8, 
CYP2C9, CYP2C19, CYP2D6 or CYP3A4/5 and no induction of CYP 1A2, 2B6 or 
3A4/5 enzyme activity or gene expression was observed.  Therapeutic proteins have been 
shown to cause suppression of cytochrome P450 and drug transporter activities and 
expression however GSK2587916 is unlikely to modulate the cytokines which are known 
to elucidate this mechanism. Together these data suggest cys-mcMMAF and 
GSK2587916 have a low risk of being perpetrators of drug interactions. 
1.2.4.
Toxicology of GSK2857916 (anti-BCMA MMAF)
The potential toxicity of GSK2857916 [aBCMA antibody drug conjugate (CA8 J6M0 
Potelligent MMAF)] has been evaluated in rat and cynomolgus monkeys in single dose 
range toxicity studies and in repeat dose studies of 3-weeks duration by the intravenous 
route of administration. An in vitro cross-reactivity study was conducted to evaluate the 
binding of GSK2857916 to human tissues. 
1.2.5.
Repeat dose toxicity
In the definitive 3 week rat and monkey toxicity studies, GSK2857916 was administered 
by the intravenous route formulated as a solution in 25mM aqueous Citrate buffer 
containing 0.05mM EDTA, 200mM Trehalose and 0.02% Polysorbate 80 (pH 6), and 
administered to rats at a dose volume of 10 mL/kg (10 minute infusion) and to monkeys 
at a dose volume of 4 mL/kg/dose (bolus, slow push).
1.2.5.1.
Rat
GSK2857916 [0 (vehicle), 3, 10 or 30 mg/kg] was given once weekly for 3 weeks by IV 
infusion to male and female rats followed by a 12 week off dose period (0, 3 and 
30 mg/kg/week). All changes presented are times control values.


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One female given 30 mg/kg died in the restraint tube prior to dosing on Day 8; however, 
as 1 control animal died immediately after removal from the restraint tube on completion 
of dosing on Day 1, this death was considered not to be test article-related.
Adverse microscopic changes in the testes were noted at 10 mg/kg/week (degeneration 
and atrophy of seminiferous tubules which correlated with macroscopic findings of 
reduced size/flaccid testes and lower testes weights (down to 0.50X control). At 
30 mg/kg/week, adverse microscopic changes were also noted in the kidney (tubular 
degeneration, characterised by basophilia, single cell necrosis and often, with hyaline cast 
formation) with associated increases in urine albumin (up to 549X), total protein (up to 
14X), NAG (up to 1.3X), GST (up to 5.4X), lipocalin-2 (up to 58X), KIM-1 (up to 
3.4X) and RPA-1 (up to 2.4X); and plasma urea (up to 1.22X) and calcium 
concentrations (up to 1.13X) and sternum/bone marrow, decreased cellularity (minimal to 
moderate) accompanied by single cell necrosis with associated changes in red cell 
parameters [decreased red blood cells (down to 0.81X)], hemoglobin and hematocrit 
(down to 0.75X), mean cell volume and mean cell hemoglobin (down to 0.92X) and 
increased high absorption reticulocytes (1.97X) and decreased medium and low 
absorption reticulocyte counts (down to 0.45X)] at the end of the treatment period. In 
addition, in the lung, eosinophilic material (tubular-myelin) accompanied by multifocal 
macrophage aggregates, frequently subpleural, with alveolar wall thickening and in some 
foci, perivascular mononuclear inflammatory cell infiltration, was noted at the end of the 
off-dose period. Macroscopically many pale areas were noted in the lungs of these 
animals. 
Non adverse microscopic and clinical pathology changes were noted at 30 mg/kg in the 
mandibular and mesenteric lymph nodes (multinucleate giant cells), femur/femorotibial 
joint (bone remodelling, characterised by osteoblast hypertrophy/hyperplasia, 
scalloped/uneven bone surfaces, fibrosis or early hyperostosis), and male mammary gland 
(epithelial single cell necrosis) as well as lower body weight gain (0.53X) and food 
consumption (0.91X) and increased total protein (1.29X), immunoglobulin A (1.78X) and 
higher alpha 1 and beta electrophoresis (up to 2.1X), cholesterol and potassium (1.47X) 
concentrations, changes in triglyceride concentrations, decreased bilirubin (0.59X) and 
lower WBCs (down to 0.47X), reflecting lower neutrophil, lymphocyte, monocyte, 
eosinophil and basophil counts. 
At 10 mg/kg non-adverse findings were noted in the epididymides 
(aspermia/hypospermia, reduced size, mixed interstitial inflammatory cell infiltration), 
ovaries (luteinized nonovulatory follicles), spleen (lymphocytolysis, increased pigmented 
macrophages, congestion, higher weights), sternum/bone marrow (decreased cellularity/ 
single cell necrosis/ bone remodelling, characterised by osteoblast 
hypertrophy/hyperplasia, scalloped/uneven bone surfaces, fibrosis or early hyperostosis), 
liver (extramedullary haematopoeisis, increased weights), injection site (local epidermal 
hyperplasia/perivascular inflammation/skeletal muscle degeneration/necrosis), and 
thymus (lymphocytolysis accompanied by decreased cellularity and mixed inflammatory 
cell infiltration the interstitial and surrounding connective tissue and lower weights) as 
well as higher platelet counts (2.1X) and red cell distribution width (1.37X) higher 
neutrophil and basophil counts (2.5X) and increases in AST (6.8X), aldolase (3.4X), 


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creatinine kinase (2.8X), ALP (up to 3.0X), ALT(3.5X), glutamate dehydrogenase 
(GLDH) (8.6X), alpha 1 acid glycoprotein and IgM. 
At all doses findings non-adverse findings were noted in the lung (eosinophilic material 
(tubular-myelin) accompanied with prominent alveolar macrophages) and eye (minimal 
bilateral corneal single cell necrosis, without ophthalmology findings) as well as higher
albumin (1.13X), lipcalin-2 (7.5X) and alpha 2 macroglobulin (1.76X) concentrations.
In addition, increases in cytokine levels from 24 hours after the start of dosing on Day 1 
was observed with higher monocyte chemoattractant protein-1 (up to 3.1X), IL-1(up to 
1.93X), IL-6 (up to 3.9X) and TNF-concentrations (up to 3.1X) noted at 30 mg/kg, and 
IL-6 (up to 1.74X) and TNF-(up to 2.3X) concentration in females only noted at 
10 mg/kg. No associated treatment-related changes in body temperature or associated 
clinical signs were noted. 
Following the 12 week off dose period, in animals previously given 30 mg/kg/week, 
there was recovery of the changes in all tissues except the lungs and testes/epididymides 
(seminiferous tubular atrophy and aspermia) together with additional clinical 
(discoloration, unevenly/abnormally worn, appearing longer, thicker or shorter) and 
microscopic changes (degeneration of ameloblast layer) in continuously growing incisor 
teeth. Body weight gain increased between Days 22R and 39R (1.21X) and lower from 
Day 39R (0.82X) onwards, food intake (0.94X) continued to be lower in males. Liver 
(1.14X) and spleen weights (1.23X) were still increased in males, thymus weights 
(0.78X) were reduced and some clinical pathology parameters were still altered in some 
animals after the off-dose period including increased urine albumin excretion levels (up 
to 40X), cholesterol (up to 1.27X), higher reticulocyte counts (up to 1.98X), red cell 
distribution width (up to 1.14X), WBC (up to 1.39X) and lymphocyte (up to 1.56X) 
counts.
Findings of uncertain relationship to treatment comprised a diffuse decrease in 
vacuolation in the brown adipose tissue of 1 female given 30 mg/kg at the end of the 
treatment period, and an increase in the incidence of hyaline casts in the kidneys of off-
dose animals previously given 30 mg/kg. 
There were no changes considered related to GSK2857916 administration in the stage 
dependent evaluation of spermatogenesis following treatment at 3 mg/kg/week. Changes 
in the testes at higher doses precluded sperm staging evaluation in these animals.
Due to the adverse microscopic changes in the testes at 10 mg/kg, the no observed 
adverse effect level (NOAEL) was 3 mg/kg [mean AUC0-168h: 6100 g.h/mL, range: 5960 
to 6240 g.h/mL, and mean Cmax: 103 g/mL, range: 101 to 105 g/mL (based on gender 
averaged Day 15 values for GSK2857916 ADC)].
1.2.5.2.
Cynomolgus monkey
In the 3-week definitive study in cynomolgus monkey, GSK2857916 was given to 
monkeys (3/sex/group) at 0 (vehicle), 1, 3 and 10 mg/kg/week once weekly for 
approximately 3 weeks by intravenous injection (bolus, slow push).  An additional 2 


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monkeys/sex/group were added at doses of 0 and 3 mg/kg/week to evaluate the 
reversibility of potential test article related effects following a 12-week off-dose period. 
Test article-related microscopic inflammatory changes were noted in the spleen and bone 
marrow.  In the spleen and bone marrow, an increase in macrophages, characterized by 
increased numbers of vacuolated macrophages containing variable amounts of brown 
pigment, engulfed cellular and/or nuclear debris, was present in the red pulp of monkeys 
given ≥3 mg/kg/week (minimal to mild) or in the bone marrow of monkeys given 
10 mg/kg/week (mild to moderate).  These microscopic effects in spleen and bone 
marrow at 3 mg/kg/week were reflective of a systemic inflammatory response at 
increasing doses and were not noted following the off-dose period.  
The inflammatory microscopic changes in spleen and bone marrow noted at terminal 
necropsy correlated with clinical pathology findings at Day 22 consistent with an 
inflammatory response including dose responsive increases in mean serum C-reactive 
protein concentrations (up to 36X baseline) at 3 mg/kg/week, decreased serum albumin 
concentrations for individual monkeys given 3 mg/kg/week, and increases in mean total 
white blood cells, principally neutrophils, monocytes and large unstained cell counts, at 
10 mg/kg/week.  The systemic inflammatory response was also associated with a mild 
decrease in red cell mass parameters (to 0.82X baseline) and platelet counts (to 0.70X 
baseline), with evidence of regenerative responses in individual monkeys including 
reticulocytosis and release of nucleated red blood cells at 10 mg/kg/week.  These changes 
were noted with histologic splenic and marrow macrophage changes which, upon 
cytologic evaluation of bone marrow smears, were suggestive of hemophagocytosis.  
These clinical pathology changes noted in monkeys given 3 mg/kg/week were not noted 
at the end of the off-dose period.
In the liver, Kupffer cell effects characterized by an overall increase in visible Kupffer 
cells and with occasional presence of mitotic figures were noted in monkeys given 
3 mg/kg/week.  In the kidney, minimal increases in mitotic figures of mesangial cells 
were present in renal glomeruli of monkeys given 10 mg/kg/week.  Also associated in 
some of the affected kidneys, was an increase in mitotic figures within interstitial 
histiocytic cells of the renal cortex.  
In the kidney of a single male given 10 mg/kg/week, a mild glomerulopathy was noted 
microscopically, characterized by expansion of the mesangium by a homogenous 
eosinophilic matrix.  Also present in the same monkey, there was mild 
degeneration/regeneration of the distal nephron, characterized by clustered distal tubules 
that were dilated and with basophilic cytoplasm and euchromatic nuclei.  Single cell 
necrosis was present in the collecting duct epithelium.  Rare tubules contained 
proteinaceous fluid or blood.  These findings correlated with significantly elevated urine 
albumin and total protein excretion values in this animal on Day 22 and were considered 
an effect of the test article.   The constellation of clinical pathology and microscopic 
findings are consistent with a primary, test article-related injury to glomeruli, with 
subsequent tubule/duct injury.
Increased tingible body macrophages were microscopically present in the thymic cortex 
of monkeys given ≥3 mg/kg/week and were often associated with intracytoplasmic 


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phagocytized cellular and nuclear debris (lymphocytolysis) or decreased cortical 
thickness.  Several monkeys given 10 mg/kg/week additionally had decreased cellularity 
of the cortex associated with the tingible body macrophage finding and variable thymic 
weights at 10 mg/kg/week. These findings were not considered to be adverse. 
Decreases in absolute number and percentage of natural killer (NK cells) were observed 
on Day 22 in monkeys given 10 mg/kg/week, as well as in individual monkeys given 
3 mg/kg/week.  There was evidence of reversibility at the end of the 12-week off-dose 
period in monkeys given 3 mg/kg/week.  Additionally, minimal increases in absolute 
number and percentage of activated (CD69+) B cells were observed on Day 22 in 
monkeys given 10 mg/kg/week; however, activated B cells represent a small proportion 
of total B cells (0.6 and 1.1% CD69+ mean for males and females, respectively, at 
baseline) and changes were not detected in the absolute number or percentage of total 
B cells.  There were no test article-related changes in absolute number or percentage of 
T cells, CD4 and CD8 T cell subsets, or NK T cells following administration of 
GSK2857916.
Mean serum immunoglobulin M (IgM) concentrations were decreased (0.77X to 0.48X 
baseline) for males given 3 mg/kg/week and females given 1 mg/kg/week on Day 22 
and were also decreased (0.54 to 0.66X baseline) following the off-dose period.  Mean 
serum immunoglobulin G (IgG) concentrations for individual females given 
10 mg/kg/week were decreased (0.78X baseline) on Day 22.  These decreases in IgM and 
IgG were expected changes consistent with the pharmacologic activity of the test article 
on plasma cells.
Mean serum aspartate aminotransferase (AST) (to 13X baseline), glutamate 
dehydrogenase (GLDH) (up to 3.3X baseline), gamma glutamyltransferase (GGT) (to 
2.0X baseline), total bilirubin (to 1.7X baseline) and/or alanine aminotransferase values 
(ALT) (to 2.2X baseline) for male and female monkeys given 10 mg/kg/week were 
increased on Day 22, but were not associated with correlative hepatocyte or biliary 
microscopic findings.  
The mean serum cholesterol concentration for males given 10 mg/kg/week was increased 
(1.52X baseline) and mean serum triglyceride concentration for females given 
10 mg/kg/week was increased (2.2X baseline) on Day 22.  
Increased mean activated partial thromboplastin times for males and females given 
10 mg/kg/week were noted on Day 22 and were considered test article-related but 
non-adverse based on low magnitude and lack of correlate clinical findings.  
Reduced eating (greater than half the daily allotment of food remaining) was noted 
sporadically throughout the dosing phase in monkeys given 10 mg/kg/week with a 
decrease in the consumption of citrus fruit in females given 3 mg/kg/week.   Body 
weight loss was noted by 4 days following the last dose in 1 female at each dose level 
(non-fasted).  A fasted terminal body weight prior to necropsy (8 days following the last 
dose) showed a slight increase from the previous weight for the female given 
1 mg/kg/week, while that for the female given 10 mg/kg/week remained unchanged.  The 
affected female given 3 mg/kg/week was maintained throughout the off-dose period and, 


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in the beginning of this phase, body weight continued to decrease.  The body weight for 
this female generally increased throughout the remainder of the off-dose period and was 
comparable to Day 1 values by the end of the off-dose period.
Stage dependent qualitative evaluation of spermatogenesis in the testes was not 
performed on male monkeys due to immaturity of testes.  
Based on glomerulopathy and degeneration/regeneration noted in the distal nephron in 
the kidney of the male given 10 mg/kg/week, the highest non-severely toxic dose was 
3 mg/kg/week.
Based on adverse findings noted at 3 mg/kg/week and the transient nature of the body 
weight change noted in the monkey given 1 mg/kg/week, the no-observed-adverse effect 
level was 1 mg/kg/week [GSK2857916 (ADC): AUC0-167  1240 g.h/mL, range 893 to 
1470 g.h/mL; Cmax 27.5 g\mL, range 22.7 to 32.9 g/mL; GSK2857916 (Total) AUC0-
167 1520 g.h/mL, range 1210 to 1700 g.h/mL; Cmax 27.3 g\mL, range 22.4 to 31.7 
g/mL; cys-mcMMAF: AUC0-167  12.1 ng.h/mL, range 6.01 to 23.1 ng.h/mL; Cmax 0.499 
ng\mL, range 0.341 to 1.03 ng/mL (gender-averaged based on Week 3 values)].
1.2.6.
Genotoxicity
Intact biopharmaceutical therapeutics, such as monoclonal antibodies and antibody drug 
conjugates, do not directly interact with DNA or other chromosomal material.  Therefore, 
genetic toxicology studies with GSK2857916 were not performed. The active moiety of 
GSK2857916 is MMAF cytotoxin which is expected to be genotoxic in mammalian 
systems given it is a microtubule disrupting agent.
1.2.6.1.
Route assessment for genotoxic impurities
An assessment of the route of synthesis for GSK2857916 has been carried out to 
determine the likelihood of mutagenic impurities being present in the drug substance. 
This indicated that there are no impurities of known or potential mutagenic concern that 
are considered likely to be present in final drug substance at a level that would exceed the 
threshold of toxicological concern at the planned clinical dose range. 
1.2.7.
Local tolerance
Clinical and histopathological analysis of injection sites was incorporated into the dose 
range toxicity and 3-week definitive repeat dose toxicity studies in rats and cynomolgus 
monkeys.
In the rat dose range toxicity study mild epidermal hyperplasia with single cell necrosis 
and mild degeneration/necrosis of skeletal muscle with inflammatory cell infiltrate was 
noted at the injection site in animals intravenously administered a bolus injection of 
GSK2857916 at  ≥ 30 mg/kg (dose concentrations 6 and 16.1 mg/mL). In the rat 3-week 
study intravenous infusion of GSK2857916 at doses ≥ 10 mg/kg (dose concentrations 1 
and 3 mg/mL) caused localised epidermal hyperplasia at the injection site. Focal skeletal 
muscle degeneration/necrosis was also observed in 1 male given 30 mg/kg. In addition, 


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the incidence of perivascular inflammation at the injection site was increased in 
GSK2857916 treated animals at doses of ≥3 mg/kg (dose concentration 0.3 mg/mL). 
In the monkey dose range toxicity study mild to minimal hemorrhage with minimal to 
moderate subcutaneous inflammation characterised by necrosis, mixed inflammatory cell 
infiltrate including lymphocytes and large histiocytes/fibroblastic cells occasionally with 
multinucleation and mitotic figures and/or fibrosis was observed at ≥3 mg/kg (dose 
concentration 16.1 mg/mL) following bolus intravenous injection. In the female given 30 
mg/kg epidermal squamous cell hyperplasia was also seen. No treatment related changes 
at the injection site were observed in the 3-week monkey study following repeated bolus 
intravenous administration of GSK2857916  at doses of 1, 3 and 10 mg/kg (dose 
concentrations 0.25, 0.75 and 2.5 mg/mL).
1.3.
Benefit:Risk Assessment
Summaries of findings from non clinical studies conducted with GSK2857916 can be 
found in the Investigator’s Brochure [GlaxoSmithKline Document Number 
2013N175128_02].  The following section outlines the risk assessment and mitigation 
strategy for this protocol:  
1.3.1.
Risk Assessment
Nephrotoxicity
Non clinical safety experiments have demonstrated primary glomerular injury and tubular 
degeneration (in rat at doses 30mg/kg, and in monkey at doses 10mg/kg). The 
morphologic changes were accompanied by large molecular proteinuria (albuminuria). 
The renal changes were dose dependent and reversible. 
To minimize the risk of nephrotoxicity, only subjects with well-preserved kidney 
function will be allowed on study. During the study subjects will be monitored for 
kidney function by assessing creatinine value and clearance, electrolytes (Potassium, 
Calcium, Phosphorus, and Magnesium), protein and albumin excretion in 24 hr urine 
collection at every cycle, or more frequently if clinically indicated. Subjects will be 
educated about the need of maintaining adequate urinary output. Treatment will be 
implemented according to clinical practice. Dose reductions and treatment stopping 
criteria will be applied according to Section 3.10.
Hepatotoxicity
Non clinical safety experiments demonstrated increased liver weight and elevated liver 
enzymes at doses of 30 mg/kg in rats. Elevations in liver enzymes were also observed in 
monkeys at doses of 10 mg/kg, in addition at 3 mg/kg increased mitotic figures in 
Kupffer cells were also observed in monkeys. All of these changes were dose dependent 
and reversible. 
Only subjects with well preserved liver function will be allowed on study. Subjects with 
Hepatitis B (HBV) and C will be excluded from the trial.  Liver function tests will be 
frequently monitored in all subjects on study and in case of liver abnormalities 


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management will be implemented according to clinical practice. Subjects that meet liver 
stopping criteria (Section 3.9.1) will be withdrawn from the study.
Hematologic toxicity
Slight hemoglobin and platelet decrease together with an increase in numbers of 
neutrophils and monocytes have been noted in monkeys at doses of 10mg/kg. In rats, 
decrease in hemoglobin, white cells, lymphocytes and neutrophils were noted at doses of 
30mg/kg.  However, rats given 10mg/kg showed higher neutrophil counts, and 
increased platelets at doses of 10mg/kg. 
The complete blood count (CBC) will be assessed frequently to monitor for hematologic 
toxicity. Supportive therapy (growth factors, transfusions, antibiotics, monitoring and 
active treatment of infections) will be provided according to standard medical practice 
and dose reductions or treatment discontinuations will follow recommendations in 
Section 3.10.1.
Immunosuppression
In non clinical studies GSK2857916 has been associated with decrease in 
immunoglobulins in monkeys (IgM at doses 1mg/kg, and IgG at >10 mg/kg).  An 
increase in immunoglobulins was seen in rats (IgM 10mg/kg and IgA at 30 mg/kg).  
Note that rats are not an antigen specific species for GSK2857916. 
Lymphocyte counts will be followed throughout the study by CBC and lymphocyte sub-
population analysis. Subjects will be actively monitored for immunoglobulin levels and 
treated for infections according to standard practice.
Pulmonary toxicity
Preliminary non clinical safety experiments have demonstrated the presence of 
microscopic changes in the lungs (prominent alveolar macrophages associated with 
flocculent eosinophilic material; mixed perivascular inflammation) in rats at all doses 
tested. 
Subjects will be monitored for clinical signs and symptoms potentially related to 
pulmonary toxicity.  Further diagnostic tests and management will be implemented 
immediately according to recommendations provided in Section 3.10.1.
Ocular toxicity
There were no eye related findings in monkeys.  Minimal corneal single cell necrosis was 
noted in rats treated at 3mg/kg.  
Subjects will be actively monitored for ocular toxicity and will be instructed to use 
preventive steroid eye drops as outlined in Section 3.9.8.  In case of developing eye-
related symptoms, subjects will be evaluated by an ophthalmologist and appropriate 
management will be initiated immediately.  Dose reduction and treatment stopping 


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recommendations will be followed according to recommendations provided in Section 
3.10.
1.3.2.
Benefit Assessment
Currently there is no clinical evidence that treatment with GSK2857916 will result in any 
benefit to subjects.  However, based on data from non clinical studies there is a 
possibility that GSK2857916 might reduce tumor burden in subjects with MM and 
BCMA positive lymphomas.
1.3.3.
Overall Benefit:Risk Conclusion
Overall, due to limited clinical experience with GSK2857916 benefit/risk cannot be 
asseesesed at this time.  The safety of subject is the primary objective of this study and 
adequate monitoring and guidance for dose reductions/stopping criteria are provided in 
the protocol to minimize risks associated with exposure to GSK2857916. 
2.
OBJECTIVE(S), ENDPOINT(S) AND HYPOTHESIS
Hypothesis
GSK2857916 can be safely administered to subjects with MM and with other BCMA 
positive malignancies at doses where target engagement can be demonstrated.
Objective
Endpoint
Primary

To determine safety, 
tolerability, maximum 
tolerated dose (MTD), and 
recommended phase (RP2) 
dose and schedule of 
GSK2857916 administered

Adverse events (AE) and changes in clinical signs 
and laboratory parameters 
Secondary 

To evaluate the 
pharmacokinetic (PK) 
profile of GSK2857916 and 
the breakdown product cys-
mcMMAF) after 
intravenous (IV) single and 
repeat dose administration 
in subjects with 
relapsed/refractory MM and 
BCMA expressing 
lymphomas

GSK2857916 and cys-mcMMAF PK parameters 
following IV single and repeat dose administration 
during dose escalation as data permit (e.g., AUCs 
Cmax, tmax, CL, VSS, t½ [single dose], Cmax and 
Ctrough [repeat dose]). GSK2857916 population 
PK parameters in expansion cohorts at the RP2 
dose (e.g. clearance (CL), volume of distribution 
(Vd)), and relevant covariates which may 
influence exposure (e.g. age, weight, or disease-
related covariates e.g. BCMA expression) 


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Objective
Endpoint

To assess anti-drug 
antibody (ADA) formation 
after IV single and repeat 
dose administration of 
GSK2857916

ADA incidence and titers after single and repeat 
IV dosing of GSK2857916

To explore the initial anti-
tumor activity of 
GSK2857916 in subjects 
with relapsed/refractory 
MM and BCMA expressing 
lymphomas

Clinical activity measured as Overall Response 
Rate (ORR) which is defined as follows:
o
For MM: the percentage of subjects 
achieving confirmed partial response or 
better (PR) 
o
In addition, the percentage of subjects with 
minimal response (MR) will be assessed 
for clinical benefit rate (CBR) (Appendix 
1)
o
For Lymphomas: the percentage of subjects 
achieving PR or better (PR) (Appendix 2) 
Exploratory 

To evaluate PD markers in 
MM after treatment with 
GSK2857916

sBCMA levels, BCMA receptor occupancy and 
cell death markers in subjects with MM. 

To explore relationships of 
GSK2857916 plasma 
concentrations/exposure 
with pharmacodynamics 
(PD), safety and clinical 
activity 

Relationship between receptor occupancy, tumor 
cell death markers, sBCMA and GSK2857916 
plasma PK parameters;

Relationship between safety/clinical activity (e.g. 
ORR) and GSK2857916  PK parameters 

To characterize the 
relationship between 
clinical response and other 
biologic tumor 
characteristics (DNA, 
protein analysis)

BCMA expression levels on malignant cells as 
measured by IHC and/or flow cytometry in tumor 
tissue, serum sBCMA levels and their relationship 
to clinical response

To investigate the 
relationship between genetic 
variants in the host and 
response to study medicine 
or susceptibility, severity 
and progression of disease

Relationship between host genetic variation and 
response to study medicine or susceptibility, 
severity and progression of disease


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Objective
Endpoint

To explore the effect of 
GSK2857916 on symptoms
(including bone pain, 
fatigue and visual 
symptoms) and impacts on 
HRQoL in subjects with 
relapsed/refractory MM
(Part 2)

Changes from baseline in bone pain/fatigue and 
analgesic use as measured by the eDiary

Interviews with subjects to further characterize 
changes in symptoms (including bone pain, 
fatigue and visual symptoms) and impacts on 
HRQoL

To explore changes in visual 
symptoms and function 
following discontinuation of 
treatment with 
GSK2857916

Changes in visual symptoms and impacts as 
measured by the OSDI and NEI-VFQ-25 
following treatment discontinuation

Follow-up telephone interviews conducted to 
further understand subjects experience with visual 
symptoms and changes in symptoms and related 
impacts following treatment discontinuation

To explore the initial anti-
tumor activity of 
GSK2857916 in subjects 
with relapsed/refractory 
MM in terms of time-to-
event (TTE) endpoints (Part 
2 MM)

Time to progression (TTP), defined as: the time 
from first dose until the earliest date of PD per 
International Multiple Myeloma Working Group 
(IMWG), or death due to PD.

Duration of response (DOR), defined as: the time 
from first documented evidence of PR or better; 
until the time when disease progression (PD) is 
documented per IMWG; or death due to PD occurs 
in subjects who achieve a response, i.e. confirmed 
PR or better.

Time to response (TTR), defined as: the time 
between the date of first dose and the first 
documented evidence of response (PR or better).

Progression-free survival (PFS), defined as: the 
time from first dose until the earliest date of 
disease progression (PD) per IMWG, or death due 
to any cause.

Number of deaths


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3.
INVESTIGATIONAL PLAN
3.1.
Discussion of Study Design
Table 3
Study Design
Part 1 Dose Escalation (n=up to 30 subjects)
Population:  relapsed/refractory MM
Characterize safety, PK, PD, immunogenicity and establish RP2 dose of GSK2857916
Schedule 1: GSK2587916 once every 3 weeks (21-day cycle) (n=~20)
Schedule 2: GSK2587916 once weekly for 3 consecutive weeks, 1-week rest (28-day cycle) 
(n=~9)
Serial PK samples will be collected from all subjects in Part 1
Part 2 Expansion Cohort(s)  (n=~50 subjects)
Population:
1)
Subjects with relapsed/refractory MM (up to 40 subjects)
2) Subjects with  lymphomas expressing BCMA (up to 10 subjects)
Cohort Expansion groups: Further evaluate the safety, PK, immunogenicity, and activity of 
GSK2857916 at the RP2 dose identified in Part 1
A futility analysis based on ORR data will be performed after approximately 15, 22 and 30  
subjects have been evaluated for response in MM cohort
Both Expansion groups will be analyzed separately
Sparse PK samples will be collected from all subjects
Genetics research samples will be collected predose from all subjects
This is a First Time in Human (FTIH), open-label, dose escalation trial consisting of two 
parts: a Part 1 dose escalation phase and a Part 2 expansion phase for safety, and clinical 
activity testing (Table 3 and Section 3.2). The study will enroll a total of approximately 
80-95 subjects with relapsed/refractory MM or other BCMA-expressing lymphomas.  
The maximum dose to be administered in this trial will not exceed 5 mg/kg.
Part 1: Dose-escalation cohorts will characterize the safety, tolerability, PK, and PD of 
GSK2857916 given on a once every 21 days or a once weekly schedule. Only subjects 
with MM will be enrolled in Part 1 based on an N-CRM dose escalation model until 
MTD(s) or RP2D is/are established on an appropriate schedule(s). GSK2857916 and cys-
mcMMAF PK parameters derived from extensive PK sampling and PD biomarkers (e.g. 


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target engagement/tumor cell killing) will be estimated/measured during dose escalation 
to inform the next cohort dose and the selection of a RP2 dose [Biologically effective 
dose (BED) or maximum tolerated dose (MTD)].  In case of insufficient sample quality 
or due to high variability in the measurement of PD biomarkers, up to 6 additional 
samples from subjects in expansion cohort might be collected for PD analysis.  Initially, 
GSK2857916 will be administered (IV) via 60 min infusion once every three weeks (21 
days = 1 cycle) on Schedule 1. Once an MTD1 or RP2D has been established on the once 
every 21-day (Schedule 1), the safety, tolerability, PK, and PD of once-weekly dosing 
(Schedule 2) of GSK2857916 may be explored as an additional cohort(s). Dose 
escalation decisions on each of these two dosing schedules will utilize a separate N-CRM 
model.  The information gained from evaluation of Schedule 1 (once every three weeks; 
21-day cycle) will be utilized to inform the model for Schedule 2 (once weekly for three 
consecutive weeks, 1 week rest; 28-day cycle).
Part 2: Expansion cohorts will assess the safety, tolerability, PK (sparse sampling), and 
clinical activity of the GSK2857916 dose regimen identified in Part 1.  A total of 
approximately 50 subjects will be enrolled in Part 2. A MM cohort (up to 40 subjects) 
will be enrolled with no prospective BCMA screening required (BCMA expression data 
collection and retrospective analysis will be performed).  In addition, futility analyses 
will be performed on the MM cohort after approximately 15, 22 and 30 evaluable patients 
have been assessed for response.  For more detailed information on the futility analysis, 
see Section 13.6.2. Sparse PK sampling will be collected to further characterize 
GSK2857916 exposure for the selected dose schedule.  
A smaller cohort of subjects with BCMA positive lymphomas (up to 10 subjects) will be 
enrolled based upon prospective detection of positive BCMA tumor cell expression as 
determined by a central laboratory using a validated IHC assay.  
Protocol waivers or exemptions are not allowed.  Therefore, adherence to the study 
design requirements, including those specified in the Time and Events Tables 
(Section 7.1) are essential.
Supplementary study conduct information not mandated to be present in this protocol is 
provided in the accompanying Study Procedures Manual (SPM).  The SPM will provide 
the site personnel with administrative and detailed technical information that does not 
impact subject safety.


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3.2.
Study Schematic
MTD1
4
3
1
2
25% of MTD1/RP2D1
MTD2/RP2D2
BCMA-positive Lymphomas (n =≈10)
Multiple myeloma  (n ≈ 40)
PART 1: Dose Escalation
(n≈30)
PART 2: Expansion Cohorts 
(n≈50)
2
3
1
*Cohort size to increase, n≈3 if ≥Grade 2 
drug related toxicity reported
5-9
4
RP2D1
Abbreviations: MTD=maximum tolerated dose; N-CRM= Neuenschwander Continual Reassessment 
Method; RP2D=recommended phase 2 dose
1.
Part 2 to initiate after  once every 3 week recommended dose is determined
2.
Dose escalation with once weekly schedule may commence in parallel to Part 2 expansion
3.3.
Part 1: Dose-Escalation Phase
Only subjects with MM will be enrolled in Part 1, and no prospective selection by BCMA 
expression level will be required.  The MTD of GSK2857916 will be established first on 
Schedule 1; the once every three weeks (21 days) schedule as described in Section 3.3.1. 
Subjects on Schedule 1 will be enrolled into dose escalation cohorts based on an N-CRM 
dose escalation model generated for each schedule.  
After the MTD1 or RP2D is established for the once every three weeks Schedule 1, once 
weekly dosing of GSK2857916 (Schedule 2) may be evaluated prior to, or in parallel 
with the expansion phase as described in Section 3.3.2.  A weekly dosing regimen may be 
chosen for further evaluation if toxicity is felt to be related to Cmax and that equivalent 
or greater exposures in terms of AUC can be safely achieved with weekly dosing 
compared with the once every 3 weeks dosing regimen.  


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Note:  For details on data dissemination and communication with sites (dose escalation 
meetings and safety update meetings), refer to Section 12.1.
3.3.1.
Dose Escalation on Schedule 1 (GSK2857916 administered once 
every three weeks; 21 days = 1 cycle)
(Note: For details on scheduled procedures in subjects given GSK2857916 on 
Schedule 1 in Part 1 refer to Time and Events Section 7.1.1.1)
3.3.1.1.
Single Subject Cohort Run-in (Schedule 1 only)

A single subject will be enrolled at each dose level as outlined in Table 4 until 
occurrence of a ≥ Grade 2 toxicity for which relationship to the investigational 
agent cannot be ruled out.

Initially, GSK2857916 will be administered (IV) via 60 min infusion once every 
three weeks (21 days = 1 cycle) on Schedule 1. One subject or the sentinel 
subject i.e., the very first subject on the study; will initially be enrolled at the 
starting dose of 0.03 mg/kg in Cohort 1 (Refer to Section 3.6.4 for starting dose 
rationale).  The initial dose will be given to the sentinel subject.  Serial blood 
samples will be collected for PK.  The sentinel subject must remain under 
observation for at least 24 hours after dosing before discharge.  GSK2857916 
(intact and total [intact + unconjugated antibody]) and cys-mcMMAF plasma 
concentrations will be analyzed and reviewed together with the safety data (DLT 
period). If the first dose is considered tolerated, the sentinel subject will be 
allowed to stay on the study and receive subsequent doses at the same dose level 
(i.e., 0.03 mg/kg) as scheduled, every three weeks (21 days interval) for up to 16 
doses (or until disease progression, toxicity or withdrawal of consent). 

If the sentinel subject does not experience a ≥ Grade 2 toxicity for which 
relationship to the investigational agent cannot be ruled out during the first cycle 
(within 21 days), the next subject will be allowed to enroll in the next cohort at a 
dose increased by ≤100% of the starting dose. Dose escalation with increments 
up to 100% of the previous dose will continue with enrolment of 1 subject per 
cohort until the occurrence of the first ≥ Grade 2 toxicity for which relationship 
to the investigational agent cannot be ruled out. (run in procedure outlined in 
Table 4)

The single subject (small cohort) run-in will be halted when the first ≥ Grade 2 
toxicity for which relationship to the investigational agent cannot be ruled out
occurs in one subject in Cycle 1 (21 days).  At this point, the cohort will be 
expanded to 3 or more subjects at the same dose level and the escalation will 
continue to follow the N-CRM procedure as outlined in Table 4


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Table 4
Single Subject (Small Cohort) Run-In Procedure for GSK2857916 
given on Schedule 1 (once every 21 days)
Dose Level 
Number of subjects 
with ≥G2 toxicity
Dose Escalation/Action
Dose Level 1/Cohort 1
0 out of 1 subject
(Sentinel subject)
Predicted starting dose 0.03 mg/kg every 21 
days
Dose Level 2/Cohort 2
0 out of 1 subject
Escalate to the next dose level with increase   
≤100%  of the starting dose
Dose Level 3 and 
beyond/Cohort 3 and 
beyond
0 out of 1 subject
Escalate to the next dose level with increase of 
≤100% of the dose tested in the previous cohort 
1 out of 1 subject*
Switch to Cohort size of 3 or more subjects 
*Increase of doses up to 100% of the previous dose may continue until the first ≥Grade 2 
toxicity for which relationship to the investigational agent cannot be ruled out occurs in 
one subject in Cycle 1 (21 days).  At this point the single subject (small cohort) run-in is halted.  
Continue with N-CRM, with cohort sizes of 3 or more subjects.  Increase of doses 100% will be 
considered for subsequent cohorts of 3 or more subjects. 

Dose escalation/de-escalations decisions will take into account all available data, 
including but not limited to the safety parameters, PD and PK data of all cohorts 
assessed.  Dose escalation/de-escalation decisions will be informed by the N-
CRM [Neuenschwander, 2008].  The N-CRM model used for Schedule 1 is 
described in detail in Section 3.3.1.2.  The method is fully adaptive and makes use 
of all DLT information available at the time of each dose assignment.  The Fixed 
and Adaptive Clinical Trial Simulator (FACTS) will be used to conduct the N-
CRM.  Dose-related decisions will occur following review of these data by the 
investigator(s), GSK medical monitor, clinical pharmacology modelling and 
simulation (CPMS) representative, and statistician. The decision and rationale 
will be documented in written format and distributed to the investigator(s), GSK 
medical monitor, CPMS representative, and statistician.

The MTD will be defined as that dose which has the highest probability of having 
a DLT rate within the target toxicity interval, and for which the probability that 
the DLT rate lies within the excessive toxicity or the unacceptable toxicity 
window is less than 25% (see Section 3.3.3 for DLT definitions).  The DLT
assessment period on Schedule 1 will be 21 days.

Dose adjustments/stopping criteria will adhere to guidelines provided in Section 
3.10.1.

Selected dose escalation cohorts may enroll additional subjects in order to further 
assess safety, PK and/or PD.  The frequency and schedule of dosing may be 
adjusted based on emerging safety, PK and PD data e.g., a recovery period may 
be incorporated into the dosing. Additional, intermediate dose levels may also be 
explored. 


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
Subjects will receive GSK2857916 treatment until disease progression, 
unacceptable toxicity, withdrawal of consent, or until they have reached the end 
of the treatment period, which has been pre-specified as 16 cycles (48 weeks) for 
Schedule 1 (GSK2857916 given once every three weeks; 1 cycle = 21 days).
3.3.1.2.
Description of N-CRM for Schedule 1
3.3.1.2.1.
Planned Dose Levels
Prior to the start of the study, projected dose levels on Schedule 1 (in mg/kg) are 0.03, 
0.06, 0.12, 0.24, 0.48, 0.96, 1.92, 2.8, 3.6, and 4.5 mg/kg; actual dose levels will be 
determined by N-CRM (Neuenschwander-Continuous Reassessment Method).  
Additional doses and schedules may be explored based on emerging safety, PK, and PD 
data. The maximum dose to be administered in this trial will not exceed 5 mg/kg.
Description of the New Continuous l Reassessment Method: After each cohort, a 
dosing recommendation for the next cohort will be made using the N-CRM 
[Neuenschwander, 2008].  All available data, including safety, PK and PD data from 
current and prior cohorts will be reviewed at the dose escalation meeting (see Section 
12.1). Although the N-CRM will be used to recommend the next dosing level, clinical 
judgment by the Medical Monitor and internal dose-escalation committee in consultation 
with the investigators can halt enrolment into lower dose cohorts as deemed appropriate 
at any time during the trial. 
The N-CRM design is a type of Bayesian adaptive dose escalation scheme that assumes a 
two-parameter logistic model for the toxicity rate based on dose.  It is a modified version 
of the original Continuous Reassessment Method [O’Quigley, 1990]. A CRM-based 
design uses a statistical model for dose and toxicity, and is expected to locate the MTD 
efficiently while minimizing the number of subjects exposed to pharmacologically 
inactive dose levels. 
The method is fully adaptive and makes use of all the DLT information available at the 
time of each dose assignment.  In contrast, the 3+3 method only uses information from 
one dosing cohort at a time.  
At the time of each dose escalation decision, the Fixed and Adaptive Clinical Trial 
Simulator (FACTS) will be used to obtain, for each potential dose, the posterior 
probabilities that the DLT rate for that dose lies in each of four toxicity intervals (under 
dosing, target dose range, excessive toxicity, and unacceptable toxicity).  The four DLT 
toxicity intervals are defined as follows:

[0%, 16%) Underdosing 

[16%, 33%) Target toxicity 

[33%, 60%) Excessive toxicity 


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
[60%, 100%) Unacceptable toxicity
The recommended dose will be the dose with the highest posterior probability of lying in 
the target toxicity interval with the additional requirement that the sum of the posterior 
probabilities of the DLT rate lying in the excessive toxicity or unacceptable toxicity 
range is less than 25%.  Selection of the next dose cohort to be enrolled is also subject to 
the constraint that the next dose level can be no more than two times that of the current 
dose level. An updated estimate of the toxicity curve will be provided at the time of each 
dose escalation meeting (see Section 12.1).
Note that de-escalation as well as escalation is possible using this method.
Dose escalation will continue until:
i)
Six subjects have been treated at the current target dose 
AND
For the current dose level, the posterior probabilities of the DLT rate lying 
within the excessive toxicity interval or within the unacceptable toxicity 
interval sum to less than 25%.
AND
For the next higher dose, the posterior probabilities of the DLT rate lying 
within the excessive toxicity interval or within the unacceptable toxicity 
interval sum to less than 25%.
OR
ii)
No doses are usable (i.e.  For ALL doses, the posterior probabilities of the 
DLT rate lying within the excessive toxicity interval or within the 
unacceptable toxicity interval sum to more than 25%
AND
At least two DLTs have been observed.
The N-CRM model used to determine the MTD for Schedule 1 will utilize a single 
subject/cohort run-in phase.
3.3.1.2.2.
Implementation of N-CRM
The N-CRM model implementation will be performed using Fixed and Adaptive Clinical 
Trial Simulator (FACTS) (Version 2.3 or higher) from Tessella.


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3.3.1.2.3.
Bayesian Prior
The N-CRM methodology requires that a Bayesian prior for the toxicity curve be pre-
specified.    
The proposed prior probabilities of DLT are an approximation on the potential toxicity 
profile based on the available non clinical toxicology package, dosing range being 
considered, and literature data available from clinical trials with other ADCs. 
Additionally, the prior is considered a ‘weakly informative prior’ and is defined with a 
fairly wide credible interval. This allows the model the freedom to estimate the observed 
probabilities of toxicity with minimal restriction.
The initial Bayesian prior used for this design is determined by using the quantile 
method.  For each dose, an estimate of the median probability of DLT was specified, 
along with a 95% credible interval.  The 95% credible intervals are intentionally wide 
due to limited information about the toxicity profile of GSK2857916 in humans.  Table 5
shows the median prior probability of experiencing a DLT at the given dose along with a 
95% credible interval around the median:
Table 5
Table of Specified Prior Probability of DLT (with 95% Credible 
Interval)
Anticipated Dose
(mg/kg)
2.5% Quantile for 
Probability of 
Toxicity
Median 
Probability of 
Toxicity
97.5% Quantile for 
Probability of Toxicity
0.03
0
0.001
0.80
0.06
0.01
0.02
0.82
0.12
0.02
0.05
0.84
0.24
0.03
0.1
0.86
0.48
0.05
0.15
0.88
0.96
0.07
0.2
0.90
1.92
0.1
0.225
0.92
2.8
0.11
0.275
0.94
3.6
0.12
0.35
0.96
4.5
0.13
0.425
0.98
A graphical presentation of the initial prior is displayed in Figure 1.  Doses are the 
projected doses.  Actual doses used during the conduct of the trial may vary. An 
intermediate prior will be derived based on the initial prior by FACTS (Version 2.3 or 
higher) from Tessella. The final prior is determined based on the intermediate prior and 
all available data.


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Figure 1
Graphical display of the prior distribution for the probability of DLT 
given dose
3.3.2.
Dose Escalation on Schedule 2 (GSK2857916 administered once 
weekly x3, 1 week rest; 28 days = 1 cycle)
(Note: For details on scheduled procedures in subjects given GSK2857916 on Schedule 2 
in Part 1, refer to Time and Events Table in Section 7.1.1.2)
The MTD (MTD1) or RP2D (RP2D1) established for GSK2857916 on Schedule 1 i.e., 
once every three weeks schedule, will inform selection of the starting dose for Schedule 2 
i.e., the once weekly schedule.  Additional cohort(s) may be enrolled to evaluate the 
safety, PK, and PD of GSK2857916 for the once weekly dosing schedule to establish an 
MTD2.  GSK2857916 will be dosed once weekly for 3 consecutive weeks, followed by 1 
week off (Schedule 2 = 28-day cycle). 

The once weekly dosing cohorts may be explored prior to, or in parallel with, 
enrollment to the expansion cohorts (Part 2).

The dose escalation of the once weekly schedule will utilize a separate N-CRM 
model from the model used for the once every three week schedule. The 
information gained from the evaluation of the once every three week schedule 
(Schedule 1) will be utilized to more accurately define the N-CRM model used 
for dose escalation on the once weekly schedule (Schedule 2).

Depending on emerging safety signals, the proposed weekly starting dose will be 
25% of MTD1 or RP2D1.  If the initial dose of 25% of MTD1 or RP2D1 is not 
tolerated, dose escalation on the weekly schedule will be terminated and 
enrollment into Schedule 2 will be closed.  If the starting dose is tolerated, 
escalation on the weekly schedule will continue at increments of 30% and will 
follow the N-CRM procedure until MTD2 or RP2D2 is reached. 

The MTD will be defined as that dose which has the highest probability of having 
a DLT rate within the target toxicity interval and for which the probability that the 


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DLT rate lies within the excessive toxicity or the unacceptable toxicity window is 
less than 25% (see Section 3.3.3 for DLT definitions).  The DLT assessment 
period on Schedule 2 will be 28 days.

The N-CRM procedure for the weekly schedule will not utilize a single 
subject/cohort run-in phase. Schedule 2 dose escalation cohorts will consist of 3 
or more subjects due to higher starting dose and greater probability of toxicity.

Dose escalation decisions will also take into account all available data. This 
includes, but is not limited to the safety and PK characteristics of all cohorts 
assessed.  In addition, dose escalation decisions will be determined by the N-
CRM [Neuenschwander, 2008].  The FACTS will be used to conduct the N-CRM.  
These decisions will occur following review of these data by the investigator(s), 
GSK medical monitor, CPMS representative, and statistician.  The decision and 
rationale will be documented in written format and distributed to the 
investigator(s), GSK medical monitor, CPMS representative, and statistician.  

Dose adjustments/stopping criteria will adhere to guidelines provided in Section 
3.10. 

Subjects will receive GSK2857916 in this weekly dosing cohort until disease 
progression, unacceptable toxicity, withdrawal of consent, or completion of the 
pre-specified treatment period of 48 doses (16 cycles on Schedule 2).

If a subject misses a dose on the weekly schedule, the dose will be recorded as 
missing and the next dose will be administered according to the current cycle.  
The counting of days and cycles will continue regardless of whether or not the 
subject received the dose.  Dose delays of + 3 days are allowed in order to 
accommodate scheduling conflicts/holidays, etc.
Additional alternative schedules may be evaluated based on emerging data. If an 
alternative schedule other than the weekly dosing schedule is evaluated, details on 
dosing and Time and Events will be updated in the Study Procedures Manual (SPM).
3.3.3.
Dose-Limiting Toxicity - Part 1 only
Any subject in Part 1 (Dose Escalation) who received at least one dose of the drug 
(regardless of schedule) will be evaluated for DLTs.  Safety data together with DLTs will 
be reviewed during the dose escalation meetings prior to opening enrollment into 
subsequent cohorts (see Section 12.1). 
Subjects who have been withdrawn from the study for reasons other than toxicity but 
prior to completion of DLT observation period will be replaced.An event will be 
considered a DLT if its relationship to the investigational agent cannot be ruled out 
occurs within the DLT reporting period (first 21 days of treatment for schedule 1, and 
first 28 days for schedule 2) and meets one of the following criteria:


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
Albuminuria ≥2000 mg/24 hr which has been confirmed by repeat test at least 7 
days apart and is not considered to be related to disease progression based on 
consultation of investigator with GSK medical monitor

Grade 4 neutropenia (without fever) lasting 7 days 

Febrile neutropenia lasting 72 hours 

Grade 3 thrombocytopenia associated  with bleeding where estimated blood loss 
is > 10mL or Grade 4 thrombocytopenia lasting >7 days and not responding to 
platelet transfusions 

Any Grade 3 or greater non-hematologic toxicity as described in Common 
National Cancer Institute-Terminology Criteria for Adverse Events (NCI-
CTCAE) version 4.0 [NCI, 2009]  with the exception of the following Grade 3 
events that can be controlled within 48 hours with routine supportive measures
o
Nausea and vomiting that can be controlled with anti-emetics
o
Diarrhea that can be controlled with anti-diarrheals
o
Rash or other skin reactions that can be controlled with antihistamines and 
steroids
o
Clinically asymptomatic electrolyte abnormalities which can be corrected 
within 48 hours)

Liver toxicity meeting pre-specified GSK liver stopping criteria (see Liver in 
Section 3.9.1)
Tumor lysis syndrome does NOT constitute a DLT (Section 3.9.7).
A subject who develops a DLT will be allowed to stay on study only if the toxicity did 
not meet stopping criteria and recovered to Grade 1 within 14 days, or after a longer 
recovery time if benefit to subject can be demonstrated and if the investigator and 
medical monitor agree that for a given subject the benefits may outweigh the risks.
3.3.4.
Maximum Tolerated Dose
The MTD will be defined as that dose which has the highest probability of having a DLT 
rate within the target toxicity interval and for which the probability that the DLT rate lies 
within the excessive toxicity or the unacceptable toxicity window is less than 25%.
3.4.
RP2 Dose and Administration Schedule Selection for Part 2
All available safety, PK, and PD data from the once every 3 weeks schedule, and if 
available, the once weekly dosing schedule, will be analyzed. If a consistent level of 95-
100% receptor occupancy is observed in evaluable subjects at a dose lower than the 
determined MTD with no evidence of target mediated disposition in the PK profile and 
where emerging signs of clinical activity can be demonstrated, a dose level below MTD 
may be defined as the biologically effective dose (BED).
This lower dose level, or an intermediate dose considered the BED, may be tested as the 
RP2 dose for further evaluation in Part 2.  Part 2 may start enrolling once Part 1 has 


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completed enrollment of Schedule 1 (once every three weeks) and after the preliminary 
PK and relevant PD data have been analyzed. The once weekly schedule may be explored 
prior to or in parallel with the expansion cohorts. Data considered will include, but not be 
limited to,  relationships between safety and exposure, the PK profiles, as well as any 
emerging PD information, and early signs of clinical activity observed for each schedule 
evaluated in Part 1. If the once weekly schedule is explored prior to initiating Part 2, the 
chosen dosing regimen would need to provide evidence of the following in order to be 
the preferred schedule in Part 2:  a better safety and tolerability profile at an equivalent or 
higher dose, or greater clinical activity, or a more desirable PK profile (i.e. no evidence 
of target-mediated disposition observed over the dosing interval).  A preference might be 
given to the weekly schedule if at MTD1, the receptor occupancy levels are considered 
sub-optimal and/or saturation of soluble sBCMA is not maintained long enough on the 
every 3 weeks dosing schedule.
Part 2: Expansion Cohort:
(Note: For details on scheduled procedures in subjects given GSK2857916 in Part 2, refer 
to Time and Events Tables Section 7.1.2. The Time and Events Table for GSK2857916 
administered to MM subjects on Schedule 1 is represented in Section 7.1.2.1, and the 
Time and Events Table for GSK2857916 administered to MM subjects on Schedule 2 is 
represented in Section 7.1.2.2. Refer to Time and Events Tables Section 7.1.2.3 and 
Section 7.1.2.4 for GSK2857916 administered to subjects with lymphomas on Schedule 1 
or Schedule 2, respectively).
Once the RP2 dose and schedule have been selected, expansion cohorts will be enrolled 
in order to better characterize the safety profile of the selected dose and schedule.  

The Part 2 expansion will enroll up to 50 subjects as summarized below:
o
Multiple Myeloma cohort (up to 40 subjects)- no prospective screening of 
BCMA is required for enrollment

Futility analyses based on ORR will take place after approximately 
15, 22 and 30 subjects have been evaluated for response. Full 
details can be found in Section 13.6.2  

BCMA expression data and retrospective analysis will be 
performed on samples collected in the MM population

PRO will be collected via eDiary in the MM population in Part 2 
only

BCMA positive lymphomas (defined as BCMA positive staining 
by IHC)  (up to 10 subjects) – prospective screening of  BCMA 
expression is required for enrollment

Sparse PK sampling will be collected from all subjects in Part 2 to explore exposures 
of GSK2857916 at the RP2 dose (BED or MTD) and schedule.  Genetics research


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samples will also be collected as outlined in Section 7.6 and in the Time and Events 
Table in Section 7.1.2.
Note:  For details on data dissemination and communication with sites (safety update 
meetings), refer to Section 12.1.
3.5.
Intra-Subject Dose Escalation
For the subjects enrolled in Part 1, intra-subject dose escalations may be considered on a 
case-by-case basis, provided that the subject completed at least 2 cycles at originally 
assigned dose, still fulfils eligibility criteria, has tolerated treatment well, and did not 
experience Grade 3 or higher toxicity. A subject’s dose may be increased to that of a 
completed cohort that has not exceeded the MTD. Approval must be obtained from a 
GSK Medical Monitor. Dose-escalation decisions will be documented on a Dose 
Escalation/De-escalation Decision Form (see SPM).
3.6.
Rationale
3.6.1.
Rationale for Study
This study will assess the safety, PK, PD and the therapeutic potential of GSK2857916 in 
subjects with MM and lymphomas that express BCMA. GSK2857916 is a humanized 
IgG1 antibody drug conjugate (ADC) which binds specifically to BCMA. The parent 
anti-BCMA antibody (J6M0) is conjugated to the microtubule inhibitor monomethyl 
auristatin-F (MMAF) via a protease resistant maleimidocaproyl (mc) linker to produce 
the GSK2857916 ADC molecule.  Upon binding to the cell surface, GSK2857916 is 
rapidly internalized and active drug (cys-mcMMAF) is released inside the cell.
GSK2857916 has been produced in an afucosylated form to generate an enhanced 
antibody dependent cellular cytotoxicity (ADCC) response upon binding to FcRIIIa 
receptors on the surface of human effector cells. This dual mechanism of action may 
improve efficacy by targeting dividing and non-dividing tumor cells. Importantly, BCMA 
expression is maintained at the cell surface over time following GSK2857916 binding 
and internalization due to rapid BCMA receptor recycling and/or new protein synthesis.  
GSK2857916 has demonstrated dose-dependent cytotoxic activity in myeloma cell lines, 
ex vivo primary myeloma tumor samples, as well as preclinical myeloma mouse tumor 
models.  GSK2857916 has also shown activity in B cell lymphoma cell lines that express 
BCMA.
The hypothesis is that GSK2857916 can be safely administered to subjects with BCMA 
positive malignancies at doses where target engagement can be demonstrated.  This study 
will determine if adequate target engagement of BCMA receptors translates into clinical 
benefit for subjects with MM and BCMA positive lymphomas. 
3.6.2.
Rationale for Population
The anti-tumor activity of GSK2857916 relies strictly on its binding to the BCMA cell 
surface receptor. Following binding to receptor the drug will be internalized and the toxin 
(MMAF) will be released inside the cell to cause cell cycle arrest and subsequent death.  


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In addition, the antibody on the cell surface will recruit effector cells via the ADCC 
mechanism to kill the tumor cells.  It is prudent that the target population for this study is 
required to express BCMA.  The MM population has been selected for this FTIH trial 
because this population has the highest likelihood of expressing BCMA.  BCMA 
expression levels in MM vary from patient to patient, but our studies demonstrate that all 
MM patients tested express detectable levels of BCMA protein on their tumor cells.  
Specifically, GlaxoSmithKline (GSK) studies have shown that in samples taken from 
MM patients (N=45), 31% have low expression, 38% moderate expression and 31% high 
expression of BCMA as detected by immunohistochemistry (IHC).  Subjects with 
lymphomas that exhibit BCMA expression have been selected as an exploratory cohort in 
this FTIH study; the frequency of BCMA expression in lymphomas is lower than that 
observed in MM, therefore prospective selection is required.  
The target population for this study includes subjects with relapsed/refractory MM to 
establish the dose and characterize safety, PK and PD of GSK2857916.  Subjects with 
BCMA expressing lymphomas will also be allowed on study after prospective screening 
by IHC demonstrates that BCMA is expressed on tumor cells. Potential subjects with B-
cell lymphomas that will be tested for BCMA expression prior to study entry include
subjects with the following diseases:  Diffuse Large B-Cell Lymphoma (DLBCL), or
Follicular Lymphoma (FL), that have progressed after 2 prior lines of systemic therapy 
for a given disease.  
3.6.3.
Rationale for Starting Dose
The dose selection of GSK2857916 in this proposed first time in human study (FTIH) 
took into consideration both the ADC and enhanced ADCC mechanisms that are 
combined in this molecule and was based on estimations derived from different 
approaches that included non clinical biology, toxicology as well as pharmacokinetic data 
collected in two species in particular mouse and monkey.
The following methods were used to support the determination of the starting dose:

methods specific for oncology compounds based on results of toxicology studies 
(for ADC mechanism)

Minimum Anticipated Biological Effect Level (MABEL) (for ADCC mechanism)
3.6.3.1.
Human PK prediction
The human PK profile of GSK2857916 was predicted using the monkey pharmacokinetic 
data collected during the pre-clinical development of GSK2857916. Analysis of the 
monkey pharmacokinetic data using a 2-compartment PK model provided estimates of 
PK parameters in this species. In these conditions, the clearance of GSK2857916 in the 
monkey was 0.00242 L/h or 19.6 mL/day/kg, the volume of distribution was 0.310 L or 
105 mL/kg and the half-life was approximately 5 days. An allometric scaling approach 
was used to predict the PK parameters in humans, with powers of unity for volume and 
0.75 for clearance. Assuming a bodyweight of 70 kg for humans, the predicted human 
clearance (CL) is 0.0259 L/h or 8.89 mL/day/kg, the volume of distribution (Vss) is 7.33 
L or 105 mL/kg and the plasma elimination half-life is approximately 12 days in the 


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absence of target.  Predicted human exposure at different doses with the predicted safety 
cover in relation to the monkey (cross-reactive species) and rat (non-target specific) 
exposure was determined assuming no target mediated disposition and in the absence of 
soluble BCMA (most conservative case), therefore human predicted exposure (i.e. AUC 
and Cmax) as well as the ratio predicted Cmax/IC50 will be likely over-estimated in 
particular at the lower doses (i.e. <1 mg/kg) (Table 6 and Table 7).
Table 6
Safety margins when comparing monkey NOAEL data (cross-
reactive species) with predicted human data for various doses of 
GSK2857916 administered IV (‘safety cover’)
Predicted Human Cmax and AUC
Safety cover (vs. Monkey NOAEL)
Ratio of predicted 
humanCmax/IC501
Dose 
(mg/kg)
Cmax (µg/mL)
AUC (µg*h/mL)
Dose cover
Cmax cover
AUC 
cover
0.03
0.593
81.0
33x
46.4x
15.3x
6.03x
0.05
0.988
135
20x
27.8x
9.2x
10.1x
0.1
1.98
270
10x
13.9x
4.6x
20.1x
0.2
3.95
540
5.0x
7.0x
2.3x
40.2x
1
19.8
2700
1.0x
1.4x
0.5x
201x
2
39.5
5400
0.5x
0.7x
0.2x
402x
5
98.8
13500
0.2x
0.3x
0.1x
1006x
1. IC50 = 0.1 μg/mL for depletion of CD19+/CD27hi/CD38hi plasmablasts in whole blood 
(ADCC mechanism)
Table 7
Safety margins when comparing rat NOAEL data (non-target 
specific) with predicted human data for various doses of 
GSK2857916 administered IV (‘safety cover’)
Predicted Human Cmax and AUC
Safety cover (vs.rat NOAEL)
Dose (mg/kg)
Cmax (µg/mL)
AUC (µg*h/mL)
Dose Cover
Cmax Cover
AUC Cover 
0.03
0.593
81.0
100x
174x
75x
0.05
0.988
135
60x
104x
45.2x
0.1
1.98
270
30x
52.1x
22.6x
0.2
3.95
540
15x
26.1x
11.3x
1
19.8
2700
3x
5.2x
2.3x
2
39.5
5400
2x
2.6x
1.1x
5
98.8
13500
1x
1.0x
0.5x


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3.6.3.2.
Starting dose determination
A summary of the in-vitro and in-vivo IC50s for both the ADC and ADCC mechanisms 
are summarized below (Table 8).
Table 8
GSK2857916 in-vitro – in-vivo IC50 Values
Mechanism
System
IC50 (ng/mL)
(range)
ADCC
(In vitro)
H929 target cells (n=8 PBMC donors) GSK
1.631 (0.57-4.79)
JJN3 target cells (n=8 PBMC donors) GSK
9.421(1.01-111.3)
primary human MM CD138+ tumor cells (n=10 
donors) Farber
~100
depletion of CD19+/CD27hi/CD38hi plasmablasts in 
whole blood (n=4 donors) GSK
981 (34-221)
H929 in presence of sBCMA
116
Cytokine induction 
from effector cells 
in vitro
Cytokines induction from PMBC in presence of H929 
target cells and GSK2857914 (ADCC enhanced only)
< 1002
ADC
(In vitro)
Across various expressing cells lines (n=12)
45.61 (3-244)
H929 target cells GSK
8.9 (8.0 – 9.8)3
JJN3 target cells GSK
25.1 (18.2 – 34.8)3
ADC
(in vivo)
Mouse xenograft
2540
1.
Geometric mean
2.
value reported is not an IC50, please refer to Section 5.6.3 of the IB for full description
3.
(95% CI) The values reported are for GSK2857916
Based on in-vitro H929 cell lines experiments, the ADCC mechanism appears to be 
approximately 5.5-fold more potent than the ADC mechanism (1.63 ng/mL versus 8.9 
ng/mL).  The same pattern is observed with the JJN3 cell lines where the ADCC 
mechanism appears to be approximately 2.7-fold more potent than the ADC mechanism 
(9.42 ng/mL versus 25.1 ng/mL).  Additionally, from the receptor occupancy curve and 
the killing activity curves for the ADCC and ADC mechanisms, it can be noted that 
maximum killing activity can be achieved at low binding.

Based on results of toxicology studies (ADC mechanism)


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Several methods were applied to look at the toxicologic aspect of GSK2857916 for the 
estimation of the starting dose based on the toxicology findings from the GLP toxicology 
studies conducted in both the rat and monkey species (refer to Section 1.2.4 for more 
details). A summary of the calculated starting dose from the different methods is 
provided in Table 9 below.
Table 9
Calculated starting dose from different approaches based on 
findings of toxicology studies
Methods
Starting dose
1/10th STD10 rat (BWT based)
1 mg/kg
1/6th HNSTD in monkey (BWT 
based)
0.5 mg/kg
1/6th HNSTD in monkey (BSA
based)
0.15 mg/kg
1/10th NOAEL in monkey 
(BWT based)
0.1 mg/kg
1/10th NOAEL in monkey (BSA
based)
0.03 mg/kg

Based on MABEL determination (ADCC mechanism)
In order to investigate the pharmacology aspect of GSK2857916, predicted receptor 
occupancy (RO), based on the binding affinity of the drug for its target and BCMA 
receptor concentration, at the predicted Cmax (assuming no target mediated disposition 
and in the absence of soluble BCMA) of various doses were estimated and summarised in 
Table 10 below.
Table 10
Predicted receptor occupancy at Cmax for various doses
Dose (mg/kg)
Cmax (µg/mL)
RO
0.03
0.593
36%
0.05
0.988
55%
0.1
1.98
81%
0.2
3.95
93%
1
19.8
99%
2
39.5
99%
5
98.8
100%
To assess the excess of drug over target, the ratio of predicted Cmax at different doses to 
the BCMA receptor concentration in the bone marrow (Table 11) was also estimated 


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based on a published estimate of the number of multiple myeloma cells [Sullivan, 1972] 
an in-house determination of the number of BCMA receptor per cell.
Table 11
Ratio of predicted Cmax to the BCMA receptor concentration in the 
bone marrow at various doses of GSK2857916
Dose (mg/kg)
Cmax (nM)
Ratio of predicted human 
Cmax/BCMA Receptor 
concentration
0.03
3.95
0.45
0.05
6.58
0.74
0.1
13.2
1.49
0.2
26.3
2.97
1
132
15
2
263
30
5
658
74
Additionally, to incorporate the dynamic aspect, a drug-receptor binding PKPD model  
was developed that incorporates the major elements believed to be involved in the drug 
disposition process (e.g. tumor load, number of BCMA receptors on multiple myeloma 
cells, internalisation rate of the complex of drug-BCMA receptor formed, shedding rate 
of the BMA receptors (soluble BCMA) based on pre-clinical data (in-vitro as well as in-
vivo) generated in house, and assumptions supported by published data in the literature. 
The model simulates the predicted level of receptor occupancy achieved over time, the 
accumulation of the molecule intracellularly via internalization of the ADC-receptor 
complex formed and consequently cys-mcMMAF, as well as the tumor regression. 
Mouse xenograft data generated during the pre-clinical development of GSK2857916 for 
which PK samples were also collected were modeled in order to derive an IC50 for tumor 
regression in relation to the cytotoxic agent (MMAF) of the molecule (ADC mechanism). 
This information was used in the drug-receptor binding PKPD model.  Predicted Cmax 
and receptor occupancy assuming a high and low tumor burden at various doses are 
presented below. Prediction incorporates target-mediated disposition and presence of 
soluble BCMA.
Table 12
Predicted Cmax and receptor occupancy assuming a high and low 
tumor burden at various doses
High tumor load
Low tumor load 
(10-fold lower)
Dose (mg/kg)
Cmax 
(µg/mL)
RO
Cmax 
(µg/mL)
RO
0.03
0.037
2%
0.30
22%
0.1
0.21
8%
1.7
52%
1
15.7
91%
21
96%
5
104
99%
108
99%


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Selection of starting dose:
In light of the potent ADCC mechanism in this unprecedented combination of enhanced 
ADCC and ADC mechanism in GSK2857916 and the novelty of the target (BCMA 
receptor), the MABEL approach to determine the starting dose was felt more appropriate. 
This is further supported by the fact that the monkey GLP toxicology study was 
conducted in healthy monkey (i.e. with no tumor) and that the mouse xenograft 
experiments did not fully explore the enhanced ADCC mechanism (human tumor but 
mouse effector cells). Furthermore, with both GSK2857916 (ADC molecule) and 
GSK2857914 (ADCC enhanced only) a general systemic inflammatory response was 
observed which could be attributable to the ADCC mechanism or related to the target 
binding.  An increase in cytokine levels was observed with GSK2857914 which again 
could be attributed to the ADCC mechanism or to target binding. Finally, in the agonism 
assay, cross-linking with GSK2857914 induced NFκB signaling in H929 cells (with an 
EC50 in the range of 0.65-1.67 g/mL). Taking into consideration all this information 
and the information derived from different methods looking at both the toxicology and 
pharmacology aspects of GSK2857916, a starting dose of 0.03 mg/kg is proposed to 
account for the ADCC mechanism of the molecule that is anticipated to occur first and is 
believed to be the most important mechanism to consider in the determination of the 
starting dose. This dose is lower than the 1/6th HNSTD in the monkey, the most relevant 
species for this molecule as it cross-reacts with monkey BCMA, based on body surface 
area. Assuming no target mediated disposition and absence of soluble BCMA, this dose 
is predicted to provide 36% receptor occupancy.  From a drug-receptor binding PKPD 
model that incorporates target mediated disposition and the presence of sBCMA, this 
dose is anticipated to confer between 2-22% receptor occupancy, depending on the tumor 
load.
3.6.3.3.
Potential therapeutic dose determination
From the drug-receptor binding PKPD model (considering target mediated disposition 
and soluble BCMA), doses in the range 1-5 mg/kg (depending on tumor load) are 
anticipated to confer maximal therapeutic activity with an average predicted receptor 
occupancy of approximately 90% over the interval between two doses (i.e. 21 days) 
following the first dose and maximal anti-tumor effect afforded by the drug. This is also 
aligned with the in-vivo IC90 (approximately 20 g/mL) for tumor regression in relation 
to the cytotoxic agent of the molecule (ADC mechanism) derived from the mouse 
xenograft data in the presence of soluble BCMA and the in-vitro IC90 for the ADCC 
mechanism of 0.5 g/mL (depletion of CD19+/CD27hi/CD38hi plasmablasts in whole 
blood) or approximately 10 g/mL (primary human MM CD138+ tumor cells).
Of note, competitor ADC molecules using MMAF as the cytotoxic agent have identified 
3 mg/kg every 3 weeks as the MTD SGN-75 [Thompson, 2013] and AGS-16M8F doses 
up to  4.8 mg/kg every 3 weeks have been reported with no MTD identified yet [Beck, 
2012].


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3.6.4.
Rationale for Endpoints
The endpoints of this study are designed to evaluate the safety, PK and PD of 
GSK2857916 in subjects with MM. Safety assessments will detect emerging safety 
signals and identify DLTs for determination of MTDs and a recommended dose and 
schedule of GSK2857916 for further exploration in expansion cohorts.
The collection of PK samples for determination of GSK2857916 plasma (intact, total 
antibody and cys-mcMMAF) concentrations will allow characterization of the PK profile 
and support investigation of its pharmacology.
Tumor biomarker selection was based on the dual mechanism of action of GSK2857916 
(ADCC and ADC activity), the need for BCMA receptor expression for GSK2857916 to 
execute its action, and preclinical evidence that BCMA is a relevant therapeutic target.  
The study will seek to characterize the PD effects of GSK2857916 and to obtain 
preliminary data on the relationship between BCMA expression and other potential 
biomarkers (e.g., sBCMA, immune associated markers, etc) that may influence clinical 
response.
Markers showing significant correlation between baseline levels and clinical outcome 
may have predictive value and maybe further explored for utility in patient selection in 
future trials.
Anti-tumor activity will be explored to evaluate the potential for clinical benefit from 
GSK2857916 treatment. In addition, patient report outcomes will also be studied in Part 2 
(MM subjects only)
3.7.
Study Treatment
3.7.1.
Treatment Assignment
Dose level allocation will be performed by GSK after subjects have given their written 
informed consent and have completed the necessary screening assessments.  

The site staff will fax and/or email a complete Registration Form to the 
designated GSK study team member.  

Subjects will be identified by a unique subject number that will remain consistent 
for the duration of the study.  The subject number will be used on all Case Report 
Form (CRF) pages and other trial-related documentation or correspondence 
referencing that subject.

Upon completion of all the required screening assessments, eligible subjects will 
be registered into RAMOS (Registration and Medication Ordering System), the 
GSK interactive voice response system (IVRS), by the investigator or authorized 
site staff.  All enrolled subjects will receive GSK2857916.
Additional details are outlined in the SPM.


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3.8.
Dosage and Administration of Study Treatment(s)
GSK2857916 will be administered intravenously over 60 minutes.  Subjects enrolled in 
Schedule 1 will receive one dose every 3 weeks (21 days) for a maximum of 16 cycles 
(16 doses).  Subjects enrolled in Schedule 2 will receive one dose per week for 3 
consecutive weeks followed by 1 week rest (28 day cycle) for a maximum of 16 cycles 
(48 doses). 
The maximum dose to be administered to subjects in this trial is 5 mg/kg.
Refer to Section 4 for details on preparation and handling, and administration instructions 
of GSK2857916.
3.8.1.
Blinding
This is an open-label study.
3.9.
Safety Management Guidelines
3.9.1.
Liver Chemistry Stopping Criteria
Liver chemistry threshold stopping criteria have been designed to assure subject safety 
and to evaluate liver event etiology during administration of study treatment(s) and the 
follow-up period.  Study treatment(s) will be stopped if any of the following liver 
chemistry stopping criteria is/are met:
1.
Alanine aminotransferase (ALT) 3 X (times) upper limit of normal (ULN) and 
bilirubin 2 Xs ULN (or ALT 3 X ULN and international normalization ratio 
[INR] >1.5)
NOTE: Serum bilirubin fractionation should be performed. 
2.
ALT 5 X ULN.
3.
ALT 3 X ULN if associated with the appearance or worsening of rash or hepatitis 
symptoms (fatigue, nausea, vomiting, right upper quadrant pain or tenderness, or 
jaundice) or hypersensitivity ( such as fever, rash or eosinophilia).
4.
ALT 3 X ULN persists for 4 weeks.
5.
ALT 3 X ULN and cannot be monitored weekly for 4 weeks.
Subjects with ALT 3 X ULN and <5 Xs ULN and bilirubin <2 X ULN, who do not 
exhibit hepatitis symptoms or rash, can continue study treatment(s) as long as they can be 
monitored weekly for 4 weeks.  See following section for details on weekly follow-up 
procedures for these subjects.
3.9.1.1.
Liver Chemistry Follow-up Procedures
Refer to the diagram in Appendix 8 for a visual presentation of the procedures listed 
below.


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The procedures listed below are to be followed if a subject meets the liver chemistry 
stopping criteria defined in Section 3.9.1:

Immediately and permanently withdraw the subject from study treatment 

Notify the GSK Medical Monitor within 24 hours of learning of the abnormality to 
confirm the subject’s study treatment(s) cessation and follow-up

Complete the “Safety Follow-Up Procedures” listed below

Complete the liver event electronic case report forms (eCRFs).  If the event also 
meets the criteria of a serious adverse event (SAE) (see Section 8.2), the SAE data 
collection tool will be completed separately with the relevant details

Upon completion of the safety follow-up permanently withdraw the subject from the 
study and do not rechallenge with study treatment(s)
Safety Follow-Up Procedures for subjects with ALT 3 times ULN:

Monitor subjects weekly until liver chemistries (ALT, aspartate aminotransferase 
[AST], alkaline phosphatase [ALP], and bilirubin) resolve, stabilize or return to 
within baseline values
Safety Follow-Up Procedures for subjects with ALT 3 times ULN and bilirubin 2 
times ULN (or ALT 3 times ULN and INR >1.5):

This event is considered an SAE (see Section 8.2).  Serum bilirubin fractionation 
should be performed. 

Make every reasonable attempt to have subjects return to the clinic within 24 hours 
for repeat liver chemistries, additional testing, and close monitoring (with specialist 
or hepatology consultation recommended)

Monitor subjects twice weekly until liver chemistries (ALT, AST, alkaline 
phosphatase, bilirubin) resolve, stabilize or return to within baseline values
In addition, for all subjects with ALT 3 times ULN, every attempt must be made to 
also obtain the following:

Viral hepatitis serology including:

Hepatitis A Immunoglobulin M (IgM) antibody

Hepatitis B surface antigen and Hepatitis B Core Antibody (IgM)

Hepatitis C ribonucleic acid (RNA)

Cytomegalovirus IgM antibody

Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, obtain 
heterophile antibody or monospot testing)

Hepatitis E IgM antibody (if subject resides outside the United States (US) or 
Canada, or has traveled outside US or Canada in past 3 months)


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
Blood sample for PK analysis.  Record the date/time of the PK blood sample draw 
and the date/time of the last dose of study treatment(s) prior to blood sample draw on 
the eCRF.  If the date or time of the last dose is unclear, provide the subject’s best 
approximation.  If the date/time of the last dose cannot be approximated OR a PK 
sample cannot be collected within 48 hours of learning of the abnormality, do not 
obtain a PK sample.  Instructions for sample handling and shipping are included in 
the SPM.

Serum creatine phosphokinase and lactate dehydrogenase

Fractionate bilirubin, if total bilirubin 2 times ULN

Obtain complete blood count with differential to assess eosinophilia

Record the appearance or worsening of clinical symptoms of hepatitis or 
hypersensitivity, such as fatigue, nausea, vomiting, right upper quadrant pain or 
tenderness, fever, rash or eosinophilia, on the AE eCRF

Record use of concomitant medication(s), acetaminophen, herbal remedies, other 
over-the-counter medication(s), or putative hepatotoxins on the Concomitant 
Medications eCRF

Record alcohol use on the Liver Events eCRF
The following are required for subjects with ALT 3 times ULN and bilirubin 2 times 
ULN but are optional for other abnormal liver chemistries:

Anti-nuclear antibody, anti-smooth muscle antibody, and Type 1 anti-liver kidney 
microsomal antibodies

Liver imaging (ultrasound, magnetic resonance imaging [MRI] or computed 
tomography [CT] scan) to evaluate liver disease

Liver Imaging and/or Liver Biopsy eCRFs are also to be completed if these tests are 
performed

Serum acetaminophen adduct HPLC assay (quantifies potential acetaminophen 
contribution to liver injury in subjects with definite or likely acetaminophen use in the 
preceding week [James, 2009]). 

Only in those with underlying chronic hepatitis B at study entry (identified by 
positive hepatitis B surface antigen):  quantitative hepatitis B DNA and hepatitis delta 
antibody.  NOTE:  if hepatitis delta antibody assay cannot be performed, it can be 
replaced with a PCR of hepatitis D RNA virus (where needed) – as outlined in: 
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1153793.
3.9.2.
QTc Stopping Criteria
Study treatment will be withheld in a subject who meets the corrected QT (QTc)1 interval 
duration criteria below.  

QT interval corrected for heart rate by Fridericia’s formula (QTcF) >500 msec
or


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
Increase in QTc of > 60 msec from baseline
1Based on average QTc value of triplicate electrocardiograms (ECGs) to include manual 
over-read.  For example, if an ECG demonstrates a prolonged QT interval, obtain 2 
additional ECGs over a brief period (e.g., within approximately 10 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 subjects 
should have study treatment withheld.
3.9.3.
Troponin Evaluation and Stopping Criteria
If post-screening, the local cTn is >Institutional ULN it is recommended that subjects 
undergo urgent evaluation of cardiac ischemia symptoms and ECG should be performed 
to rule out cardiac ischemia.  An urgent repeat of cTn value and collection of sample for 
central lab evaluation should be obtained within 24 hours.
Asymptomatic subject:
If the second value of cTn is ≤ULN the subject can continue on study with close follow 
up of symptoms, ECG, and further cTn measurements as clinically indicated
If the second value of cTn remains >ULN treatment with GSK2857916 should be 
interrupted.  The subject should undergo cardiac evaluation including ECHO testing for 
cardiac function. Any re-start of study treatment must be discussed with the GSK medical 
monitor who will consult with a member of the internal cardiotoxicity panel prior to re-
start.
If the second value of cTn exceeds the threshold for MI according to local lab parameters, 
obtain cardiology consultation immediately.  Permanently discontinue GSK2857916 and 
withdraw the subject from the study.  
Symptomatic subject: 
Obtain cardiology consultation immediately. Permanently discontinue GSK2857916 and 
withdraw the subject from the study.
3.9.4.
Left Ventricular Ejection Fraction (LVEF)
3.9.4.1.
LVEF Stopping Criteria
Echocardiography (ECHO) must be performed at Screening and as outlined in the Time 
and Events Tables (Section 7.1). Subjects who have an asymptomatic, absolute decrease 
of >15% in LVEF compared with baseline or an absolute decrease of >10% in LVEF 
compared with baseline and the ejection fraction is below 50% should temporarily 
interrupt GSK2857916 and have a repeat evaluation of LVEF within 1 week. ECHO 
should be repeated every 1 to 2 weeks for 4 weeks or until LVEF recovery to within 15% 
of baseline or to above 50% and within 10% of baseline depending on which stopping 
criteria above were met.


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
If the LVEF recovers (defined as absolute decrease 15% compared to baseline 
or 50% and absolute decrease 10% compared with baseline) at any time 
during the next 4 weeks, after consultation and approval of the GSK Medical 
Monitor, the subject may be restarted on GSK2857916 at a reduced dose. For 
such subjects, monitoring of LVEF will be performed 2, 4, and 8 weeks after 
rechallenge, and then per protocol

If LVEF does not recover within 4 weeks, treatment with GSK2857916 should 
be permanently discontinued. Ejection fraction should be monitored every 
4 weeks for a total of 16 weeks or until resolution
Subjects with Grade 3 or 4 symptomatic left ventricular systolic dysfunction must 
discontinue treatment with GSK2857916. Ejection fraction should be monitored every 
4 weeks for a total of 16 weeks or until resolution. 
Copies of all ECHOs and cardiology consultations performed on subjects who experience 
a >15% decrease in LVEF from baseline or >10% decrease in LVEF from baseline and 
whose cardiac ejection fraction is <50% will require review by a GSK medical monitor.
Instructions for submitting qualifying ECHOs/MUGAs are provided in the SPM.
3.9.4.2.
Valvular Toxicity Stopping Criteria
Subjects who develop a new asymptomatic, moderate regurgitation or stenosis by 
echocardiogram (ECHO) (Grade 2 mitral/tricuspid/aortic valvular toxicity per National 
Cancer Institute- Common Toxicity Criteria for Adverse Events [NCI-CTCAE], version 
4.0) should temporarily discontinue GSK2857916 and have a repeat evaluation by ECHO 
within 1 week.  ECHO should be repeated every 1 to 2 weeks for 4 weeks or until valve 
recovery to baseline.

If the valve recovers to baseline any time during the next 4 weeks after 
consultation and approval of the GSK Medical Monitor, the subject may be 
restarted on GSK2857916 at a reduced dose(s).  For such subjects, monitoring of 
the valve via ECHO will then be performed 2 and 4 weeks after rechallenge, and 
every 4 weeks thereafter for 8 weeks and then per protocol.

If repeat ECHO does not reveal valve recovery to baseline within 4 weeks, then 
the subject should permanently discontinue GSK2857916.  The valve should 
continue to be monitored via ECHO every 4 weeks for 8 weeks or until 
resolution.
Subjects with a Grade 3 or 4 (symptomatic, severe regurgitation/stenosis by imaging with 
symptoms controlled by medical intervention) valvular toxicity must discontinue 
GSK2857916.  Valvular toxicity should continue to be monitored every 4 weeks for 
12 weeks or until resolution.  If recovery occurs (return to baseline via imaging AND 
symptom resolution) within 4 weeks, the subject may restart GSK2857916at a reduced 
dose after consultation and approval of the GSK Medical Monitor.
ECHO must be performed at baseline and at the final study visit.  Copies of all ECHO(s) 
and cardiology consultations performed on subjects who experience valvular toxicity will 


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be required by GSK for review.  Instructions for submitting qualifying ECHOs are 
provided in the Study Procedures Manual (SPM).
3.9.5.
Infusion-related Reactions and Cytokine Release Syndrome
Premedication is not allowed prior to first infusion unless deemed medically appropriate 
by the GSK Medical Monitor in consultation with investigators following evaluation of 
infusion related reactions across cohorts. Premedication should be considered in any 
subject who experienced an infusion related reaction at first or any subsequent infusion 
with GSK2857916.
If an infusion-related reaction occurs during administration, the infusion rate may be 
reduced or halted at the discretion of the investigator and/or GSK medical monitor 
depending on the severity of the symptoms.  The subject will receive appropriate medical 
treatment.  When the subject’s condition is stable, the infusion may be restarted 
according to the judgment of the investigator.  Upon restart, the infusion rate should be 
half of the infusion rate at the time the infusion was paused.
Blood for serum cytokines should be collected in each subject who developed infusion 
related reaction regardless whether the infusion has been completed or not. The time of 
serum collection will be documented in eCRF.

Grade 1 allergic reactions or cytokine release syndrome
o
If infusion is ongoing, it may continue but subject should be monitored 
carefully to ensure that ongoing signs and symptoms do not progress and 
worsen warranting intervention as described below

Grade 2 allergic reactions and/or cytokine release syndrome 
o
Stop the infusion, follow subject frequently for clinical symptoms
o
Initiate symptoms treatment as clinically indicated 
o
Once subject has recovered to baseline and if in the opinion of the 
investigator the safety/risk benefit is favorable, consideration can be given 
to restarting the infusion at 50% of the original rate after pre-medication 
with H1 receptor antagonist and acetaminophen
o
If treatment is continued, the subject should be pre-medicated prior to each 
subsequent dose and the infusion will be administered at 50% of the 
original rate

Grade 3 or higher allergic reactions and/or cytokine release syndrome 
o
Stop infusion immediately
o
Initiate symptoms treatment as clinically indicated 
o
Do not resume infusion with GSK2857916


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o
Follow the subjects for safety as clinically indicated until toxicity resolves
o
Complete safety documentation
o
Subjects who experience Grade 3 allergic reaction will be withdrawn 
from study 
o
Further treatment with GSK2857916 in subjects who experience a Grade 
3 infusion related reaction needs to be discussed with MM prior to next 
dose administration. Those subjects will be allowed to continue on study 
after recovery of the reaction to Grade 1 but will have to receive pre-
medication prior to each subsequent dose of GSK2857916, and their 
infusion time will be extended to 2-4 hours (depending on severity of the 
reaction).  
3.9.6.
Allergic and Anaphylactic reaction
As GSK2857916 is a fully humanized ADC, it is considered unlikely for acute allergic 
reactions to occur in response to GSK2857916 exposure; however, all subjects will be 
monitored carefully for evidence of allergic response. A subject that exhibits signs or 
symptoms of severe hypersensitivity or anaphylaxis will receive appropriate medical 
treatment and be 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.
It is important to recognize early signs of an anaphylaxis reaction and appropriate 
treatment must begin immediately to prevent progression to severe anaphylaxis. Subjects 
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. 
3.9.7.
Tumor Lysis Syndrome (TLS) Prevention and Treatment 
Recommendations
Subjects with a high tumor burden with a high proliferative rate might be at risk for TLS 
and should be monitored for clinical and laboratory signs of tumor lysis. Specifically, all 
subjects with elevated uric acid (>8mg/dL, or >476mmol/L) should receive prophylaxis 
with allopurinol, or rasburicase. All subjects should be hydrated to reduce risks for renal 
toxicity and tumor lysis syndrome (TLS) with GSK2857916 treatment. Adequate fluid 
volume status should be maintained throughout treatment and blood chemistries should 


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be monitored as indicated in the Time and Events Tables in Section 7.1 or more 
frequently if clinically indicated.  Prior to the first dose in Cycle 1, all subjects should 
receive at least 250- 500 mL of intravenous normal saline or other appropriate
intravenous fluid. Additionally, 250-500 mL of intravenous fluid should be given as 
needed following GSK2857916 administration. Intravenous hydration should be 
continued, as needed, in subsequent cycles and subjects should be monitored for fluid 
overload during this period.
If the constellation of clinical and/or laboratory signs tested on Cycle 2 Day 1 indicates a 
possibility of developing TLS, subjects should be hospitalized with frequent monitoring 
of clinical signs and clinical chemistries and treated accordingly.
3.9.8.
Ocular Toxicity and Stopping Criteria
All subjects will be advised to use prednisolone phosphate 1% or dexamethasone 0.1% 
eye drop 4 times a day (QID) for 4 days starting 1 day prior to each dose. Additional use 
of lubrication eye drops (artificial tears) QID PRN throughout the trial is recommended, 
especially if subject develops any ocular symptoms. Subjects who develop Grade 3 
ocular or corneal toxicity will be allowed to continue study treatment after resolution to 
Grade 1; each case will be discussed individually between the investigator and the
Medical Monitor. Subjects who develop Grade 4 ocular or corneal toxicity will be 
permanently removed from study. Refer to Section 3.10.2 for further guidance.
3.10.
Guidelines for Events of Special Interest and Dose 
Modifications
3.10.1.
Guidelines for Events of Special Interest
The severity of adverse events (AEs) will be graded utilizing the National Cancer 
Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.  
Guidelines for dose modifications and interruptions for management of common 
toxicities associated with the study treatment are provided in this section.


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3.10.2.
Predicted Toxicities and Proposed Dose Adjustments/Stopping Criteria
Toxicity
Grade/symptoms
Recommendations
Creatinine  elevation which 
cannot be explained by 
concomitant sepsis, other 
severe infection with fever 
or dehydration
If absolute serum creatinine 
increase from baseline of > 0. 3 
mg/dL (26 mol/L) but 0.5 
mg/dL (44 mol/L)
Repeat within 48 hours

If creatinine returns to 0. 3 mg/dL (26 mol/L) above baseline
o
Continue GSK2857916 at current dose 

If creatinine remains elevated:  > 0. 3 mg/dL (26 mol/L) but 0.5 mg/dL 
(44 mol/L) from baseline
o
Continue GSK2857916 
o
Monitor creatinine at least weekly 
o
Consider 25% dose reduction if creatinine remains elevated (after 
discussion with Medical Monitor)
If absolute serum creatinine 
increase from baseline of >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 Monitor*
* Medical Monitor should consult GSK’s nephrotoxicity panel about plans to 
continue therapy
Serum creatinineGrade 3
>3.0mg/dL from baseline
or
3.0-6.0xULN

Provide appropriate medical treatment. 

Permanently discontinue treatment with GSK2857916


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Toxicity
Grade/symptoms
Recommendations
Albuminuria
>2000mg/24 hr

Re-test (at least 7 days apart). 
o
If not confirmed, continue GSK2857916 at 100% dose
o
If confirmed on re-test and no clear evidence of disease progression*

Interrupt treatment with GSK2857916

Repeat testing within 4 weeks

If albuminuria ≤2000mg/24hr may restart 
GSK2857916 with 25% dose reduction

If albuminuria remains >2000mg/24hr  after 4 
weeks; Permanently discontinue GSK2857916  and 
withdraw subject from study; provide treatment as 
clinically indicated and  follow for resolution
* Medical Monitor should consult GSK’s nephrotoxicity panel about plans to 
continue therapy
Thrombocytopenia
Grade 3: >25 and <50x109/L

Where estimated blood loss is 10 mL: withhold the treatment:

No bleeding: continue treatment with  25% dose reduction 
Grade 4: ≤25x109/L 

Withhold the dose. Consider restarting with 25% dose reduction if recovered to 
>25x x109/L  , 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 >30 x109/L within 14 days, restarting 
treatment at 50% dose reduction may be considered after discussion with the 
GSK Medical Monitor 
Febrile neutropenia
>38.3oC for> 1 hr AND ANC < 
1000/mm3

Withhold  GSK2857916, implement treatment with antibiotics, antivirals and 
antifungals, as clinically indicated, 

If resolved 14 days, may restart GSK2857916 treatment at 25% dose 
reduction


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Toxicity
Grade/symptoms
Recommendations
INR prolongation
> 1.5

Evaluate liver function and other possible causes for INR elevation (use of 
anticoagulants, work up for DIC and provide treatment as clinically indicated 
–
If subject meets liver stopping criteria:  Withdraw from study treatment
as per liver stopping criteria 
–
If subject has evidence of DIC: withdraw subject from study treatment
–
If isolated INR elevation and subject does not meet liver stopping 
criteria 
•
Withhold the dose and re-test INR within 48hrs
•
Discuss the case with Medical Monitor and consider 25% dose 
reduction  
> 2.0

Evaluate possible reasons as above, treat adequately if underlying condition has 
been identified

Restart treatment with GSK2857916 at 25-50% dose reduction if toxicity 
resolved to 1.5 baseline and after discussing the case with GSK Medical 
Monitor
>2.5

Evaluate and provide medical treatment if necessary

If INR prolongation is not related to use of anticoagulants withdraw subject 
from study treatment
Ocular/corneal  toxicity 
Grade 1

Continue treatment with current dose of GSK2857916.  

Consult ophthalmologist within 7 days
Grade 2

First occurrence:
o
Interrupt treatment with GSK2857916
o
Consult ophthalmologist immediately
o
When recovered to G1 Restart treatment with GSK2857916 at 
25%  dose reduction upon resolution to G1 

Second occurrence:
o
Interrupt treatment with GSK2857916
o
Consult ophthalmologist immediately
o
Once resolved toG1 or less: Restart treatment with GSK2857916 


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Toxicity
Grade/symptoms
Recommendations
at additional 25% dose reduction

Third occurrence:
o
Further treatment with GSK2857916 only allowed after discussion 
and in agreement with medical monitor
Grade 3

First occurrence
o
Consult ophthalmologist immediately
o
Interrupt treatment with GSK2857916
o
Once resolved to G1: Restart treatment with GSK2857916 at 
25% -50% dose reduction if the investigator and Medical Monitor 
agree that the potential benefits outweigh the risks

Second occurrence
o
Consult ophthalmologist immediately
o
Permanently discontinue treatment with GSK2857916
Grade 4

Consult ophthalmologist immediately

Permanently discontinue treatment with GSK2857916
Pneumonitis
Grade 1
Withhold dose and follow recommendations below:
Obtain high resolution chest CT if possible.

CT scan (high-resolution with lung windows) recommended

Clinical evaluation and laboratory work-up for infection

Monitoring of oxygenation via pulse-oximetry recommended

Consultation with pulmonologist recommended

If resolved: Retreatment at the full dose is possible
Grade 2
Withhold  treatment with GSK2857916
Follow recommendations below:
Obtain high resolution chest CT if possible.

CT scan (high-resolution with lung windows)

Clinical evaluation and laboratory work-up for infection

Consult pulmonologist


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Toxicity
Grade/symptoms
Recommendations

Pulmonary function tests (PFT) – if abnormal, repeat every 8 weeks until back 
to baseline 

Bronchoscopy with biopsy and/or bronchoalveolar lavage (BAL) recommended

Symptomatic therapy including corticosteroids if clinically indicated
If resolved: Restart treatment with 50% dose reduction
Grade 3/Grade 4
Permanently discontinue treatment with GSK2857916, and follow 
recommendations below.

Obtain CT scan (high-resolution with lung windows)

Clinical evaluation and laboratory work-up for infection

Consult pulmonologist

PFT – if abnormal, repeat every 8 weeks until back to baseline Bronchoscopy 
with biopsy and/or BAL if possible

Symptomatic therapy including corticosteroids as clinically indicated


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3.10.3.
Dose Modifications
For GSK2857916 toxicities not specifically addressed in the protocol follow the 
guidelines outlined in Table 13.  
Table 13
Dose Adjustment/Stopping Criteria
Toxicity Gradea
Dose Modification of GSK2857916
Grade 1

Continue at current dose level. Consider supportive care 
recommendations 
Grade 2

If toxicity is considered not clinically relevant, continue with 100% 
scheduled dose

If toxicity is considered clinically relevant withhold the dose until 
toxicity resolves to Grade 1 or baseline. If resolved within 14 days, 
then restart at current dose level. Consider supportive care 
recommendations

If not resolved within 14 days, discuss with GSK Medical Monitor 
Grade 3

Withhold dose until toxicity resolves to Grade 1 or baseline, unless 
condition fits exceptions noted below. If resolved within 14 days, 
resume treatment at dose reduced by 25% (first dose reduction), or 50% 
(second dose reduction). Consider supportive care recommendations.  
If toxicity is resolved within period longer than 14 days, continuation of 
treatment may be considered on an individual basis if benefit to 
subject can be demonstrated and if the investigator and medical 
monitor agree that for a given subject the benefits may outweigh 
the risks  
Exceptions:

Subjects who develop G3 toxicities which respond to standard treatment 
and resolve to G1 within 48 hours may continue treatment at 
scheduled or reduced dose

Permanently discontinue for grade 3 or greater QTc prolongation i.e., 
QTcF >500 msec or QTcF increase by > 60 msec from baseline

Troponin elevations: See Section 3.9.3 for troponin stopping criteria
Grade 4

Permanently discontinue study medication
Exceptions:

G4 thrombocytopenia with no sign of bleeding, if recovered within 
14 days.  For dose reductions see Section 3.10

G4 lymphopenia (dose reductions by 25-50% may be considered)
a.
Possibly related to investigational drug.


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4.
INVESTIGATIONAL PRODUCT(S)
The term ‘study treatment’ is used throughout the protocol to describe GSK2857916 as 
the investigational product (IP) received by the subject as per the protocol design.  
4.1.
Description of Investigational Product
Product name :
GSK2857916 Solution, 20 mg/mL, 1.5mL anti-BCMA-
ADC 
Formulation description:
Solution containing 20mg/mL GSK2857916
Dosage form :
Supplied as frozen liquid.  Recommended storage 
condition is -50C to -15C. 
Unit dose strength(s)/Dose Level(s):
20mg/mL, 1.5mL (Refer to Section 3.3.1.2.1 for dose 
levels)
Physical Description:
GSK2857916 Solution for Infusion is clear or opalescent; 
colorless, yellow to brown liquid 
Route/
Administration/ Duration:
Delivered as IV solution (see Section 3.8)
Dosing instructions:
Dilute GSK2857916 solution in normal 0.9% saline to the 
appropriate concentration for the dose.  See Section 4.2
for compatible administration materials.  Doses of 
GSK2857916 are to be administered as an IV infusion 
via an infusion pump that can ensure precision to the 
decimal point of a mL for the infusion rate at lower 
doses. It is recommended to prime the tubing with at 
least 15 mL prior to dosing.
Manufacturer/ Source of Procurement:
GSK
Batch Lot number
132373860
GSK2857916 will be provided to sites by GSK.  Only Batch Lot# 132373860 of drug 
product will be used for this trial. The contents of the label will be in accordance with 
all applicable regulatory requirements. The lot number indicated on the label refers to 
labelled lot number; the batch Lot# 132373860 may not be provided on the label.
4.2.
Preparation/Handling/Storage of GSK2857916 
Investigational Product
Preparation
GSK2857916 Solution for Infusion, 20 mg/mL is supplied as a frozen liquid (Lot# 
132373860).  Before use, thaw each vial of GSK2857916 for Infusion, 20mg/mL, 1.5mL 
for up to 4 hours under refrigerated conditions (2-8C), protected from light.  Following 
thawing, gently swirl the vial to ensure uniformity.  GSK2857916 should be diluted in 
normal saline (0.9%) to no more than 2 mg/mL and no less than 0.2 mg/mL. Refer to the 
Study Procedures Manual (SPM) for further details on preparation of GSK2857916.
The dosing solution of GSK2857916 can be held under refrigerated conditions (2-8C), 
for up to 24 hours (NOTE: For centers in Canada up to 8 hours only) or 4 hours at 


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ambient temperature (diluted drug product in bag) from a stability perspective, but should 
be used as soon as possible as the product does not contain an antimicrobial preservative.
Handling
Under normal conditions of handling and administration, investigational product (IP) is 
not expected to pose significant safety risks to site staff.  A Material Safety Data Sheet 
(MSDS) describing the occupational hazards and recommended handling precautions will 
be provided to site staff if required by local laws or will otherwise be available from GSK 
upon request.
In the case of unintentional occupational exposure notify the study monitor, the GSK 
Medical Monitor and/or the study manager.
Refer to the SPM for detailed procedures for the disposal and/or return of unused study 
treatment(s).
Administration
GSK2857916 is compatible with polyvinylchloride-lined or polyolefin-lined intravenous 
infusion administration sets, 0.2 micron polyethersulfone filters, or optionally a 
polyurethane catheter.  Doses of GSK2857916 are to be administered as an IV infusion 
via an infusion pump that can ensure precision to the decimal point of a mL for the 
infusion rate at lower doses. It is recommended to prime the IV tubing with at least 15 
mL prior to dosing.
Administration of drug product in this trial is restricted to Manufacturer Batch
Lot#132373869.
Storage
GSK2857916 must be stored in a secure area under the appropriate physical conditions 
for the product.  Access to and administration of the GSK2857916 will be limited to the 
investigator and authorized site staff.  GSK2857916 must be dispensed or administered 
only to subjects enrolled in the study and in accordance with the protocol.  
GSK2857916 is to be stored at a temperature range of -50C to -15C.  Maintenance of a 
temperature log is required. 
The expiry date, where required, is stated on the product label.
4.3.
Product Accountability
In accordance with local regulatory requirements, the investigator, designated site staff, 
or head of the medical institution (where applicable) must document the amount of 
investigational product (IP) dispensed and/or administered to study subjects, the amount 
returned by study subjects, and the amount received from and returned to GSK, when 


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applicable.  Product accountability records must be maintained throughout the course of 
the study.  Refer to the SPM for further detailed instructions on product accountability.
4.4.
Treatment Compliance
GSK2857916 will be intravenously administered to subjects at the study site.  The dose 
to be administered is based on body weight calculation, and may be reduced for toxicity 
according to protocol guidelines. Only two dose reductions are allowed per subject; the 
first dose reduction by 25%, and the second by an additional 25%.  If subject is not 
tolerating treatment at 50% of scheduled dose the subject will be withdrawn from study.  
Additional dose reductions (beyond 50% of the original scheduled dose) may be possible 
only for subjects who have been enrolled during dose escalation in Part 1 at the highest 
dose, which was subsequently deemed as exceeding the MTD.
The actual body weight in kg will be used for dose calculation in all subjects whose body 
weight is 100kg.  For subjects with body weight >100kg, the dose to be administered 
should be the same as that calculated for a subject weighing 100kg.  Administration will 
be documented in the source documents and reported in the electronic case report form 
(eCRF). The time of start and end of infusion will be documented in eCRF.
4.5.
Treatment of Investigational Product Overdose
In the event of an overdose (defined as administration of more than the protocol-specified 
dose) of GSK2857916, the investigator should:

contact the GSK Medical Monitor immediately

closely monitor the subject for adverse events (AEs)/serious adverse events 
(SAEs) and laboratory abnormalities until GSK2857916 can no longer be 
detected systemically (at least 3 months for GSK2857916)

obtain a plasma sample for pharmacokinetic (PK) analysis within 24 hours of 
the event if requested by the GSK Medical Monitor (determined on a case-by-
case basis)

document the quantity of the excess dose as well as the duration of the 
overdosing in the eCRF
Decisions regarding dose interruptions or modifications will be made by the investigator 
in consultation with the GSK Medical Monitor based on the clinical evaluation of the 
subject
5.
STUDY POPULATION
5.1.
Number of Subjects
The number of dose levels and the level at which the maximum tolerated dose (MTD) is 
reached cannot be determined in advance.  An adequate number of subjects will be 
enrolled into the study to establish the recommended dose(s) for further study.  It is 
estimated that approximately 30 subjects will be enrolled into Part 1, Schedule 1 (dose-


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escalation) of the study.  Up to 40 subjects with MM and up to 10 subjects with BCMA 
positive lymphomas (50 subjects total) will be enrolled in Part 2 (expansion cohort).  
The number of subjects in the expansion cohort has been estimated based on expected 
variable expression of BCMA in those subjects (about 1/3 low, 1/3 medium, 1/3 high 
expression; approximately 13 subjects/group).  The level of BCMA expression in a given 
subject is expected to impact target-mediated clearance, which as a consequence might be 
reflected in the PK/PD variability and safety profile of individual subjects.  In addition, 
the sample size of 40 subjects in the MM cohort will allow for assessment of early signals 
of clinical activity and relationships (if any) to variable target expression levels.  A total 
of approximately 80 subjects will be enrolled in the study. If Part 1, Schedule 2 (once 
weekly schedule) is explored, up to 15 additional subjects will be enrolled; then a total of 
approximately 95 subjects will be enrolled in the study.
In Part 1 (dose-escalation) of the study, if a subject has been withdrawn prior to 
expiration of the DLT observation period OR received less than 2/3 of the scheduled dose 
and is not evaluable for DLT, additional subjects may be enrolled as replacement subjects 
and assigned to the same treatment sequence at the discretion of the Sponsor in 
consultation with the investigator.
5.2.
Subject Selection Criteria
5.2.1.
Inclusion Criteria
Specific information regarding warnings, precautions, contraindications, adverse events 
(AEs), and other pertinent information on the GSK study treatment that may impact 
subject eligibility is provided in the Investigator Brochure (IB)/IB supplement(s).  
Deviations from inclusion criteria are not allowed because they can potentially jeopardize 
the scientific integrity of the study, regulatory acceptability or subject safety.  Therefore, 
adherence to the criteria as specified in the protocol is essential.
Subjects eligible for enrolment in the study must meet all of the following criteria:
1.
Provide signed written informed consent, which includes compliance with the 
requirements and restrictions listed in the consent form
2.
Male or female, 18 years or older (at the time consent is obtained)
3.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 
(Appendix 6)
4.
Part 1/dose escalation:

Histologically or cytologically confirmed diagnosis of: Multiple Myeloma in a 
subject who fulfills all of the following: 

has undergone stem cell transplant, or is considered transplant ineligible, 

has been pretreated with at least the 3 following classes of anti-myeloma 
drugs: alkylators, proteasome inhibitors and immunomodulators, 


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
has demonstrated progression on, or within 60 days of completion of the last 
therapy. 
Part 2 /MM cohort:

Histologically or cytologically confirmed diagnosis of: Multiple Myeloma in a 
subject who fulfills all of the following: 

has undergone stem cell transplant, or is considered transplant ineligible, 

has been pretreated with at least the 3 following classes of anti-myeloma 
drugs: alkylators, proteasome inhibitors and immunomodulators, 

and has demonstrated progression on, or within 60 days of completion of the 
last therapy. 

AND has measurable disease with at least one of the following:
a.
Serum M-protein 0.5 g/dL (5 g/L)
b. Urine M-protein  ≥200 mg/24h
c.
Serum FLC assay: Involved FLC level ≥5 mg/dL (≥50 mg/L) and an 
abnormal serum free light chain ratio (<0.26 or >1.65)
d. Biopsy proven plasmacytoma (should be measured within 28 days of 
Screening Visit)
or
Part 2/ BCMA positive Lymphoma cohort: 
a.
Subject with one of the following hematologic malignancies: Diffuse 
Large B-cell Lymphoma DLBCL or Follicular Lymphoma that 
exhibits positive BCMA expression on tumor cells as determined by a 
central laboratory using a validated IHC assay. Eligible subjects with 
BCMA positive lymphomas must also fulfill the prior treatment 
requirements as follows:
b. DLBCL : at least 2 prior lines of systemic therapy containing at least 
one line of chemo-immunotherapy with anti-CD20 antibody, and 
either has undergone stem cell transplant or is considered transplant 
ineligible 
c.
FL: at least 2 prior lines of systemic therapies. 
5.
Subjects 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
c.
subject meets the remainder of the eligibility criteria outlined in this 
protocol
6.
Adequate organ system functions as defined in Table 14.


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Table 14
Adequate Organ System Function
System
Laboratory Values
Hematologic
Absolute neutrophil count (ANC)1
1.0 X 109/L
Hemoglobin
8.0 g/dL
Platelets
50 X 109/L
Coagulation
INR 
1.5 
PTT
1.5 x ULN
Hepatic
Total bilirubin
≤1.5 X ULN (isolated bilirubin >1.5xULN is 
acceptable if bilirubin is fractionated and direct 
bilirubin <35%)
AST and ALT
1.5 X ULN
Renal
Serum creatinine or
Calculated creatinine clearance2
Albuminuria 
<1.2XULN
≥ 60 mL/min for Part 1;
50 mL/min for Part 2 if data supports loosening 
criteria
500mg/24hr
Cardiac
LVEF (Echo)
Troponin 
50%
1xULN
1.
Without Growth factor support for the past 14 days, excluding erythropoietin
2.
As calculated by Modified Diet in Renal Disease (MDRD) formula (Appendix 5)
NOTE:  Laboratory results obtained during Screening should be used to determine 
eligibility criteria.  In situations where laboratory results are outside the permitted range, 
the investigator may opt to retest the subject and the subsequent within range screening 
result may be used to confirm eligibility.
7.
A female subject is eligible to participate if she is of:

Non-childbearing potential (i.e. physiologically incapable of becoming pregnant) 
defined as pre-menopausal females with a documented tubal ligation or 
hysterectomy; or postmenopausal defined as 12 months of spontaneous 
amenorrhea [in questionable cases a blood sample with simultaneous follicle 
stimulating hormone (FSH) > 40 MIU/mL and estradiol < 40 pg/mL (<147 
pmol/L) is confirmatory].  Females on hormone replacement therapy (HRT) and 
whose menopausal status is in doubt will be required to use one of the 
contraception methods specified if they wish to continue their HRT during the 
study.  Otherwise, they must discontinue HRT to allow confirmation of post-
menopausal status prior to study enrollment.  For most forms of HRT, at least 2-4 
weeks will elapse between the cessation of therapy and the blood draw; this 
interval depends on the type and dosage of HRT.  Following confirmation of their 


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post-menopausal status, they can resume use of HRT during the study without use 
of a contraceptive method.

Women of childbearing potential must have a negative serum pregnancy test 
within 72 hours of first dose of study treatment and agree to use effective 
contraception, as defined in Section 11.1.1, during the study and for 60 days 
following the last dose of study treatment.
8.
Men with a female partner of childbearing potential must have either had a prior 
vasectomy or agree to use effective contraception as described in Section 11.1.2
from the time of first dose of study until 60 days after the last dose of study 
treatment to allow for clearance of any altered sperm.
9.
All prior treatment-related toxicities (defined by National Cancer Institute-
Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4) must be 
≤Grade 1 at the time of enrollment except for alopecia, and grade 2 neuropathy
5.2.2.
Exclusion Criteria
Deviations from exclusion criteria are not allowed because they can potentially 
jeopardize the scientific integrity of the study, regulatory acceptability or subject safety.  
Therefore, adherence to the criteria as specified in the protocol is essential.
Subjects meeting any of the following criteria must not be enrolled in the study:
1.
Systemic anti-tumor-therapy within 14 days, or plasmapheresis within 7 days prior 
to the first dose of study drug.
2.
Use of an investigational drug within 14 days or five half-lives, whichever is 
shorter, preceding the first dose of study drug.  Prior treatment with a monoclonal 
antibody within 30 days of receiving the first dose of study drug.  
3. History of an allogeneic stem cell transplant.  Subjects with a history of an 
autologous stem cell transplant are NOT excluded if they meet Inclusion Criterion 
#5. 
4. Presence of active renal condition (infection, requirement for dialysis or any other 
condition that could affect subject’s safety). Subjects with isolated proteinuria 
resulting from MM are eligible, provided they fulfil criteria given in Table 14.
5. Evidence of active mucosal or internal bleeding.
6. Any major surgery within the last four weeks.
7. Any serious and/or unstable pre-existing medical, psychiatric disorder, or other 
conditions (including lab abnormalities) that could interfere with subject’s safety, 
obtaining informed consent or compliance to the study procedures. 
8. Known active infection requiring antibiotic treatment.
9. Evidence of severe or uncontrolled systemic diseases (e.g., unstable or 
uncompensated respiratory, hepatic, renal or cardiac disease).
10. Subjects with previous or concurrent malignancies are allowed only if the second 
tumor is not contributing to the subject’s illness.  The subject must not be receiving 


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active therapy, other than hormonal therapy for this disease and the disease must be 
considered medically stable for at least 2 years.
11. Evidence of cardiovascular risk including any of the following:
a. QTc interval ≥ 470 msecs.
b. Evidence of current clinically significant uncontrolled arrhythmias;
a. including clinically significant ECG abnormalities including 2nd 
degree (Type II) or 3rd degree atrioventricular (AV) block.
c. History of myocardial infarction, acute coronary syndromes (including 
unstable angina), coronary angioplasty, or stenting or bypass grafting 
within six months of Screening.
d. Class III or IV heart failure as defined by the New York Heart Association 
functional classification system (Appendix 4)
e. Uncontrolled hypertension
f. Subjects with intra-cardiac defibrillators or permanent pacemakers;
g. Abnormal cardiac valve morphology (≥Grade 2) documented by 
echocardiogram (subjects with grade 1 abnormalities [i.e., mild 
regurgitation/stenosis] can be entered on study).  Subjects with moderate 
valvular thickening should not be entered on study.
12. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs 
chemically related to GSK2857916 or any of the components of the study 
treatment.
13. Pregnant or lactating female.
14. Known HIV infection.
15. Subjects with positive test for Hepatitis B surface (HBS-Ag) or Hepatitis B core 
(HBc)antigen  
16. Subjects with positive test for hepatitis C (HCV) infection are excluded regardless 
of viral load.  If hepatitis C antibody test is positive, a confirmatory polymerase 
chain reaction (PCR) or recombinant immunoblot assay (RIBA) test should be 
performed.  If the RIBA test is negative, subject is eligible for this trial.
17. Current active liver or biliary disease (with the exception of Gilbert's syndrome or 
asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease 
per investigator’s assessment).
18. Current corneal disease or a history of corneal disease. 
6.
COMPLETION OR WITHDRAWAL OF SUBJECTS
6.1.
Screen and Baseline Failures
Data for screen and baseline failures will be collected in source documentation at the site 
but will not be transmitted to GSK.


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6.2.
Subject Completion Criteria
For Part 1 (dose-escalation phase), a completed subject is one who has completed at least 
1 cycle of study treatment and an End of Study Visit without events causing them to 
withdraw or discontinue from the study for reasons listed  in Section 6.3  For Part 2 
(expansion cohort), a completed subject is one who has received at least one dose of 
study treatment without events causing them to withdraw or discontinue study treatment 
for reasons listed in Section 6.3 and completed an End of Study Visit.
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 before the end of the study, has not 
been lost to follow-up, or has not withdrawn consent from study participation.
6.3.
Permanent Discontinuation from Study Treatment
Subjects will receive study treatment until disease progression, death or unacceptable 
toxicity, including meeting stopping criteria for significant toxicity as outlined in Section 
3.10  and other relevant safety management guidelines outlined in the protocol, or until a 
maximum of 16 treatment cycles.  In addition, study treatment may be permanently 
discontinued for any of the following reasons:

deviation(s) from the protocol

request of the subject or proxy (withdrawal of consent by subject or proxy)

investigator’s discretion

a dose delay of >14 days unless the investigator or GSK Medical Monitor agree 
that subject derives benefit and that further treatment benefits will outweigh the 
risks.   Exceptions apply to nephrotoxicity as outlined in Section 3.10.2

intercurrent illness that prevents further administration of study treatment(s)

subject is lost to follow-up 

study is closed or terminated

subject completes maximum number of treatment cycles per protocol 

The primary reason study treatment was permanently discontinued must be 
documented in the subject’s medical records and electronic case report form 
(eCRF) 
If the subject voluntarily discontinues from treatment due to toxicity, ‘adverse event 
(AE)’ will be recorded as the primary reason for permanently discontinuation on the 
eCRF.
Once a subject has permanently discontinued from study treatment, the subject will not 
be allowed to be retreated. 
All subjects who discontinue from study treatment will have safety assessments at the 
time of discontinuation and during post-study treatment follow-up as specified in Time 
and Events Tables (see Section 7.1).  


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6.4.
Subject Withdrawal
Should a subject fail to attend the clinic for a required study visit, the site should attempt 
to contact the subject and re-schedule the missed visit as soon as possible. The site should 
also counsel the subject on the importance of maintaining the assigned visit schedule and 
ascertain whether or not the subject wishes to and/or should continue in the study based 
on previous non-compliance. In cases where the subject does not return for the 
rescheduled visit or cannot be reached to reschedule the missed visit, the site should 
make every effort to regain contact with the subject (3 telephone calls and if necessary a 
certified letter to the subject’s last known mailing address) so that they can appropriately 
be withdrawn from the study. These contact attempts should be documented in the 
subject’s medical record. Should the subject continue to be unreachable, then and only 
then will he/she be considered to have withdrawn from the study with a primary reason of 
“Lost to Follow-up”. For all other subjects withdrawing from the study, an alternative 
reason for discontinuation should be recorded in the eCRF.
6.5.
Study Completion
A study will be considered completed, having met the study objectives, when the last 
subject has received their last dose of study medication and completed the End of Study 
visit. 
Per the EU Clinical Trial Directive, the end of the study is defined as the last subject’s 
last visit.
6.6.
Treatment after the End of Study
The investigator is responsible for ensuring that consideration has been given for the 
post-study care of the subject’s medical condition whether or not GSK is providing 
specific post-study treatment.
Subjects’ survival and status of post-study treatment will be documented via medical 
charts analysis at 3 months following the last dose of study drug.
7.
STUDY ASSESSMENTS AND PROCEDURES
A signed, written informed consent form must be obtained from the subject prior to any 
study-specific procedures or assessments being performed.
The timing of each assessment is listed in the Time and Events Tables (Section 7.1).  The 
timing and number of the planned study assessments may be altered during the course of 
the study based on newly available data (e.g. to obtain data closer to the time of peak 
plasma concentrations) to ensure appropriate monitoring for the following assessments: 
safety, pharmacokinetic (PK), pharmacodynamic (PD)/biomarker or other assessments.  
The change in timing or addition of time points for any of the planned study assessments 
listed above must be approved and documented by GSK, but this will not constitute a 
protocol amendment.  The institutional review board (IRB) or ethics committee (EC) will 
be informed of any safety issues that require alteration of the safety monitoring scheme.  
The maximum amount of blood collected in Screening and during the first Cycle 1 from 


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each subject for the Dose Escalation and for the Dose Expansion is no more than 162 ml
of blood (See Appendix 10).
Whenever vital signs, 12-lead electrocardiograms (ECGs) and blood draws are scheduled 
for the same nominal time, the assessments should occur in the following order: 12-lead 
ECG, vital signs, blood draws.  The timing of the assessments should allow the blood 
draw to occur at the exact nominal time.  Detailed procedures for obtaining each 
assessment are provided in the SPM.
7.1.
Time and Events Tables
This section consists of the Time and Events Tables and supplemental footnotes to 
describe assessment windows and sequencing of study-specific assessments and 
procedures. 


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7.1.1.
Dose Escalation
7.1.1.1.
Every 3 Weeks Dosing Schedule for Multiple Myeloma
Time and Events Table for Full Study (Cycle = 21 days)
Study Assessments1
Screen2
Day 1 
C1
Day 2 
C1
Day 8 
C1
Day 15 
C1
Day 1 
C2
D1 of C3-C16
End of Study 
Treatment 
3-Month 
Off-study 
Follow-up
Informed Consent
X
Baseline Demographics
X
Medical History
X
Physical Exam
X
X
X
At the start of each cycle
X
Ocular Exam
X3
X4
At the start of each cycle4
X4
ECOG Performance Status
X
X
At the start of each cycle
X
Vital Signs (BP, HR, Body 
Temperature)
X
X5
X
X
X5
At the start of each cycle5
X
Weight and Height
X
Weight 
only
Weight 
only
Weight only - At the start of each cycle
Weight only
Hematology
X
X6
X
X
X
At the start of each cycle
X
Clinical chemistry
X
X6
X
X
X
X
At the start of each cycle
X
Urine Dipstick
X
X6
X
At the start of each cycle
X
INR, PTT 
X
X6
X
X
X
At the start of each cycle
HBV/HCV tests
X
CK-MB, Troponin 
X7
X7
X7
At the start of each cycle7
X7
BNP
X8
UPEP and urine 
Immunofixation
X
X
At the start of each cycle
SPEP and serum 
Immunofixation, Serum M-
protein Calculation
X
X
At the start of each cycle
Kappa, lambda free LC, FLC 
ratio
X
X
At the start of each cycle
24 hr urine protein and 
albumin
X
X
At the start of each cycle


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Time and Events Table for Full Study (Cycle = 21 days)
Study Assessments1
Screen2
Day 1 
C1
Day 2 
C1
Day 8 
C1
Day 15 
C1
Day 1 
C2
D1 of C3-C16
End of Study 
Treatment 
3-Month 
Off-study 
Follow-up
IgG, IgM, IgA
X
X
At the start of each cycle
CRP, beta2 microglobulin
X
X
At the start of each cycle
Pregnancy Test 
X9
At the start of cycles 59, 99, 139
X9
X10
Chest X-ray
X
12-lead ECG
X11
X11
X11
X11
X11
At the start of each cycle11
X11
LVEF and valves assessment 
(ECHO)
X12
At the start of cycles 412, 912
X12
Extramedullary plasmacytoma 
imaging 
X13
At the start of cycles 513, 913, 1313
X13
BM Aspirate (see below for each test required within procedure):
Disease assessment 
X14
At the time of Complete Response
BCMA assessment and 
PD (flow) 
X15
X15
FISH testing 
X16
BM biopsy for disease 
assessment and BCMA 
expression (IHC) 
X17
At the time of CR
(disease assessment only)
Serum (soluble BCMA)
X18
X18
X18
X18
X18
Predose at the start of each cycle
X18
Serum (cytokines/chemokines)
X19
X
X19
At predose and EOI on D1 of each cycle
X
Serum (anti-drug-antibodies)
X
X20
At the start of cycles 320, 620, 920, 1220 and 
1620
X
Plasma-cfDNA 
X
X 
Peripheral blood (flow for 
TBNK)
X15
X15
At the start of each cycle15
X15
Serial Pharmacokinetics 
(blood)
X21
X21
X21
X21
X21
C3D1 only21
X22
Urine PK
X23
X23
Day 1 of cycles 423, 723, 1023, 1323, 1623
Premedication if needed
X
X
At the start of each cycle
GSK2857916  administration
X24
X24
X24
Steroid eye drops
X25
X25
X25
Adverse Events
Continuous


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Time and Events Table for Full Study (Cycle = 21 days)
Study Assessments1
Screen2
Day 1 
C1
Day 2 
C1
Day 8 
C1
Day 15 
C1
Day 1 
C2
D1 of C3-C16
End of Study 
Treatment 
3-Month 
Off-study 
Follow-up
Concomitant Medications
X
Continuous
Survival Status
X26
Subsequent Treatment
X26
1.
Assessments scheduled on days of dosing should be done prior to drug administration, unless otherwise specified.  All other assessments can be 3 days of scheduled 
occurrence unless otherwise specified.
2.
All Screening assessments must be performed within 14 days prior to first dose unless otherwise specified. Informed Consent must be signed before any study-specific 
assessments are performed.
3.
Screening examination to include BCVA (best-corrected visual acuity), slit lamp examination (with special focus on cornea), intraocular pressure, and dilated fundoscopic 
examination may be performed within 21 days prior to first dose.
4.
On-study exams to include BCVA (best-corrected visual acuity) and slit lamp examination (with special focus on cornea); window for exams is up to 3 days prior to dosing.
5.
On initial (first infusion) dosing day, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +10 minutes and +30 minutes (5 min)  after SOI, EOI, and 1 
hour post EOI.  On subsequent dosing days, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +30 minutes after SOI, and EOI.  The Sentinel Subject 
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.
6.
If completed within 72 hrs prior to the first dose, this assessment need not be repeated on Day 1 of Cycle 1. Refer to Table 15 for comprehensive list of lab tests.  
7.
Troponin will be measured at the local lab (troponin I or T) and a central lab (troponin I).  CK-MB at the local lab or if not possible by a central laboratory.
8.
BNP to be measured locally, or if not available by a central laboratory, at screening; if cardiac workup is required due to safety concerns during the study, BNP should be 
measured.  
9.
Perform only in women of child-bearing potential.  A serum pregnancy test should be performed at screening, and subsequent pregnancy tests may be either serum or urine; 
10. Final pregnancy test (serum or urine) must be performed in women of childbearing potential 60 days after last study treatment.
11. On dosing days, ECG to be performed in triplicate at predose (within 30 minutes prior to SOI) and EOI.  On days where ECG timepoints align with PK sampling 
timepoints, ECGs should be performed prior to PK samples being drawn (PK sample should be taken at the exact nominal time; refer to footnote 21).  At 
screening, on interim visits (C1D8 and C1D15) and End of Study obtain a single ECG measurement.
12. At Screening, LVEF may be performed within 30 days prior to first dose. All ECHOs indicated on dosing days may be performed up to 5 days before dosing. All ECHOs to be 
done locally and sent to GSK for central imaging storage.
13. May be performed up to 21 days prior to C1D1 as screening value.  Needs to be performed by the same method throughout the study as was done at baseline (i.e. if PET 
scan was used as baseline, subject needs to be followed by PET scans).  Selected target lesion needs to be measured and followed over time.
14. Samples from within 14 days prior to first dose are acceptable.
15. Sample(s) collected for analysis by central lab.  The same sample will be used for BCMA (flow) and PD during Screening. On D8 only postdose PD assessment will be 
performed
16. 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.


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17. Archival tissue from up to 60 days prior to study is acceptable 
18. A single sample for sBCMA will be collected at C1D8, C1D15 and at the End of Study visit. sBCMA samples will also be collected on  C1D1 at predose (within 30 minutes 
prior to SOI), at EOI (5 minutes) and on C1D2 24h post SOI.  On C2D1 sBCMA will be collected pre-dose (within 30 minutes prior to SOI) and at the EOI (5 minutes)
19. Collect cytokines at predose (within 30 minutes prior to SOI) and EOI (5 min) (even when infusion is interrupted or halted) to assess allergic reaction)
20. All ADA samples will be collected prior to each infusion
21. PK samples to be taken (in all subjects) for both GSK2857916 and cys-mcMMAF measurement: C1D1 at pre-dose (within 30 minutes prior to SOI), 0.5 h after the start of the 
infusion (SOI) (5 min), at the end of infusion (EOI) just before EOI), 1 h after EOI, 3 h after EOI (5 min), 8 h after EOI (15 min), 24h after EOI (1h) (Day 2); C1D8 1 
sample; C1D15 1 sample; C2D1, at pre-dose (within 30 minutes prior to SOI) and at the EOI (just before EOI); C3D1 at pre-dose (within 30 minutes prior to SOI) and at the 
EOI (just before EOI).
22. Collect 1 PK sample at each subject’s final visit. 
23. Pre-specified amounts of urine will be collected for PK analysis from the 24 hour urine collection at Screening, C2D1, C4D1, C7D1, C10D1, C13D1, and C16D1.  Refer to 
Section 7.4.2 for details.
24. Study drug administration 3 day window only
25. Prophylaxis with prednisolone phosphate 1% or dexamethasone 0.1% 1 drop QID x 4 days starting 1 day prior to treatment
26. Record subject’s survival status and whether subsequent treatment for disease was given.  Subject does not need to come in for visit.
Abbreviations:
ADA = Antibody Drug Antibody; ALP = alkaline phosphatase; BCVA = best corrected visual acuity; BNP = B-type natriuretic peptide; C1D1 = Cycle 1 Day 1, etc.; cfDNA = 
Circulating free DNA; CK = creatinine kinase;  CRP = C-reactive protein; EM = extramedullary;  EOI = End of Infusion; FLC = free light chain; PD = Pharmacodynamics; PK = 
Pharmacokinetics; QID = 4 times a day; SOI = start of infusion; SPEP = serum protein electrophoresis; UPEP = urine protein electrophoresis
7.1.1.2.
Weekly Dosing Schedule (Dose Escalation) for Multiple Myeloma
Time and Events Table for Full Study (Cycle = 28 days)
Study Assessments1
Screen2
Day 1 
C1
Day 2 
C1
Day 8 
C1
Day 15 
C1
Day 1 
C2
D1 of C3-C16
End of Study 
Treatment
3-Month Off-
study 
Follow-up
Informed Consent
X
Baseline Demographics
X
Medical History
X
Physical Exam
X
X
X
At the start of each cycle
X


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Time and Events Table for Full Study (Cycle = 28 days)
Study Assessments1
Screen2
Day 1 
C1
Day 2 
C1
Day 8 
C1
Day 15 
C1
Day 1 
C2
D1 of C3-C16
End of Study 
Treatment
3-Month Off-
study 
Follow-up
Ocular Exam
X3
X4
At the start of each cycle4
X4
ECOG Performance Status
X
X
At the start of each cycle
X
Vital Signs (BP, HR, Body 
Temperature)
X
X5
X
X
X5
At the start of each cycle5
X
Weight and Height
X
Weight 
only
Weight
only
Weight only - At the start of each cycle
Weight only
Hematology
X
X6
X
X
X
At the start of each cycle
X
Clinical Chemistry
X
X6
X
X
X
X
At the start of each cycle
X
Urine Dipstick
X
X6
X
At the start of each cycle
X
INR, PTT
X
X6
X
X
X
At the start of each cycle
HBV/HCV tests
X
CK-MB , Troponin 
X7
X7
X7
At the start of each cycle7
X7
BNP
X8
UPEP and urine 
Immunofixation
X
X
At the start of each cycle
SPEP and serum 
Immunofixation and Serum-
M protein Calculation
X
X
At the start of each cycle
Kappa, lambda free LC, 
FLC ratio
X
X
At the start of each cycle
24 hr urine protein and 
albumin
X
X
At the start of each cycle
IgG, IgM, IgA
X
X
At the start of each cycle
CRP, beta2 microglobulin
X
X
X
At the start of each cycle
Pregnancy Test 
X9
At the start of cycles 59, 99, 139
X9
X10
Chest X-ray
X
12-lead ECG
X11
X11
X11
X11
X11
At the start of each cycle11
X11
LVEF and valves 
assessment (ECHO)
X12
At the start of cycles 412, 912
X12


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Time and Events Table for Full Study (Cycle = 28 days)
Study Assessments1
Screen2
Day 1 
C1
Day 2 
C1
Day 8 
C1
Day 15 
C1
Day 1 
C2
D1 of C3-C16
End of Study 
Treatment
3-Month Off-
study 
Follow-up
Extramedullary 
Plasmacytoma Imaging
X13
At the start of cycles 513, 913, 1313
X13
BM Aspirate (see below for each test required within procedure):
Disease assessment 
X14
At the time of Complete Response
BCMA assessment and 
PD (flow) 
X15
X15, 17
FISH testing 
X16
BM biopsy for disease 
assessment 
X18
At the time of Complete Response 
(disease assessment only)
Serum (soluble BCMA)
X19
X19
X19
X19
X19
Predose at the start of each cycle
X
Serum 
(cytokines/chemokines)
X20
X
X20
X20
X20
At predose and EOI on D1 of each cycle
X
Serum (anti-drug-
antibodies)
X21
X21
X21
At the start of cycles 321, 621, 921, 1221 and 
1621
X
Plasma-cfDNA
X
X
Peripheral blood (flow for 
TBNK and intracellular 
cytokine testing)
X15
X15
X15
At the start of each cycle15
X15
Serial Pharmacokinetics 
(blood)
X22
X22
X22
X22
X22
C3D1 only22
X23
Urine PK
X24
X24
Day 1 of cycles 424, 724, 1024, 1324, 1624
Premedication if needed
X
X
X
X
Each dosing week
GSK2857916 
administration
X25
X25
X25
X25
Each dosing week25
Steroid eye drops
X26
X26
X26
X26
Each dosing week26
Adverse Events
Continuous
Concomitant Medications
X
Continuous
Survival Status
X27
Subsequent Treatment
X27


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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 done 3 days unless otherwise 
specified.
2.
All Screening assessments must be performed within 14 days prior to first dose unless otherwise specified.  Informed Consent must be signed before any study-specific 
assessments are performed.
3.
Screening examination to include BCVA (best-corrected visual acuity), slit lamp examination (with special focus on cornea), intraocular pressure, dilated fundoscopic examination
may be performed within 21 days prior to first dose
4.
On-study exams, to include BCVA (best-corrected visual acuity) and slit lamp examination (with special focus on cornea); window for exams is up to 3 days prior to dosing.
5.
On initial (first infusion) dosing day, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +10 minutes and +30 minutes (5 min) after SOI, EOI, and 1 hour 
post EOI.  On subsequent dosing days, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +30 minutes after SOI, and EOI.  On days where vital sign 
time points align with PK sampling timepoints, vital signs should be assessed prior to PK samples being drawn.  
6.
If completed within 72 hours prior to first dose, this assessment need not be repeated on Day 1 of Cycle 1.  Refer to Table 15 for comprehensive list of lab tests.
7.
Troponin will be measured at the local (troponin I or T) and central (troponin I) lab.  CK-MB at the local lab or if not available by a central laboratory. 
8.
BNP to be measured locally, or if not available by a central laboratory, at screening; if cardiac workup is required due to safety concerns during the study, BNP should be 
measured.
9.
Perform only in women of child-bearing potential.  A serum pregnancy test should be performed at screening, and subsequent pregnancy tests may be either serum or urine.  
10. Final pregnancy test (serum or urine) must be performed in women of childbearing potential 60 days after last study treatment.
11. On dosing days, ECG to be performed in triplicate at predose (within 30 minutes prior to SOI) and EOI.  On days where ECG timepoints align with PK sampling timepoints, 
ECGs should be performed prior to PK samples being drawn (PK sample should be taken at the exact nominal time; refer to footnote 22).  At screening and at End of Study, 
obtain a single ECG measurement.
12. At Screening, LVEF may be performed within 30 days prior to first dose; All ECHOs indicated on dosing days may be performed up to 5 days before dosing.  ECHOs to be done 
locally and sent to GSK for central imaging storage.
13. May be performed up to 21 days prior to C1D1 as screening value.  Needs to be performed by the same method throughout the study as was done at baseline (i.e. if PET scan 
was used as baseline, subject needs to be followed by PET scans).  Selected target lesion needs to be measured and followed over time.
14. Samples from within 14 days prior to first dose are acceptable.
15. Sample(s) collected for analysis by central lab. The same sample collected on Day 1 of cycle 1 prior to dosing will be used for BCMA (flow) and PD u. 
16. 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.
17. Collect sample prior to dosing.
18. Archival tissue from up to 60 days prior to study is acceptable.
19. A single sample for sBCMA will be collected at C1D8 predose, and at the End of Study visit. sBCMA samples will also  be collected on C1D1 at predose (within 30 minutes prior to 
SOI), at EOI (5 minutes) and on C1D2 24h post SOI. On C1D15 and C2D1 collect at predose (within 30 minutes prior to SOI) and EOI (5 minutes)
20. Collect cytokines at predose (within 30 minutes prior to SOI) and EOI (5 min) (even when infusion is interrupted or halted) to assess allergic reaction
21. All ADA samples will be collected prior to each infusion
22. PK samples to be taken (in all subjects) for both GSK2857916 and cys-mcMMAF measurement: C1D1 at predose (within 30 minutes prior to SOI), 0.5 h after the start of the 
infusion, at EOI (just before EOI), 1 h after EOI (5 min), 3 h after EOI (5 min), 8 h after EOI (15 min), and 24h after EOI (1 h) (Day 2); C1D8 at predose (within 30 minutes 
prior to SOI), and at EOI (just before EOI); C1D15 at predose (within 30 minutes prior to SOI) and at EOI (just before EOI); C2D1 at predose (within 30 minutes prior to SOI), at 
EOI (just before EOI); C3D1 at predose (within 30 minutes prior to SOI) and at EOI (just before EOI).
23. Collect 1 PK sample at each subject’s final visit.


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24. Pre-specified amounts of urine will be collected for PK analysis from the 24 hour urine collection at Screening, C2D1, C4D1, C7D1, C10D1, C13D1, and C16D1.  Refer to Section 
7.4.2 for details.
25. Study drug administration 1 day window only.
26. Prophylaxis with prednisolone phosphate 1% or dexamethasone 0.1% 1 drop QID x 4 days starting 1 day prior to treatment
27. Record subject’s survival status and whether subsequent treatment for disease was given.  Subject does not need to come in for visit.
Abbreviations:
ADA = Antibody Drug Antibody; ALP = alkaline phosphatase; BCVA = best corrected visual acuity; BNP = B-type natriuretic peptide; C1D1 = Cycle 1 Day 1, etc.; cfDNA = Circulating 
free DNA; CK = creatinine kinase;  CRP = C-reactive protein; EM = extramedullary;  EOI = End of Infusion; FLC = free light chain; PD = Pharmacodynamics; PK = Pharmacokinetics; 
QID = 4 times a day; SOI = start of infusion; SPEP = serum protein electrophoresis; UPEP = urine protein electrophoresis


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7.1.2.
Dose Expansion
7.1.2.1.
Every 3 Weeks Dosing Schedule for Multiple Myeloma
Time and Events Table for Full Study (Cycle = 21 days)
Study Assessments1
Screen2
Day 1 
C1
Day 8 
C1
Day 15 
C1
Day 1 C2
D1 of C3-C16
End of 
Study 
Treatment34
Monthly 
Follow 
up35
Baseline Demographics
X
Medical History
X
Physical Exam
X
X
X
At the start of each cycle
X
Ocular Exam
X3
X4
At the start of each cycle4
X4
X35
ECOG Performance 
Status
X
X
At the start of each cycle
X
Vital Signs (BP, HR, 
Body Temperature)
X
X5
X
X
X5
At the start of each cycle5
X
Weight and Height
X
Weight 
only
Weight only
Weight only - At the start of each 
cycle
Weight only
Hematology
X
X6
X
X
X
At the start of each cycle
X
Clinical chemistry
X
X6
X
X
X
At the start of each cycle
X
Urine Dipstick
X
X6
X
At the start of each cycle
X
INR, PTT
X
X6
X
X
X
At the start of each cycle
HBV/HCV tests
X
CK-MB , Troponin
X7,8
X7,8
X7,8
At the start of each cycle7, 8
X7,8
BNP
X9
UPEP and urine 
Immunofixation
X
X
At the start of each cycle
SPEP and serum 
immunofixation and 
Serum M-protein 
Calculation
X
X
At the start of each cycle
Kappa, lambda free LC, 
FLC ratio
X
X
At the start of each cycle


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Time and Events Table for Full Study (Cycle = 21 days)
Study Assessments1
Screen2
Day 1 
C1
Day 8 
C1
Day 15 
C1
Day 1 C2
D1 of C3-C16
End of 
Study 
Treatment34
Monthly 
Follow 
up35
24 hr urine protein and 
albumin
X
X
At the start of each cycle
IgG, IgM, IgA
X
X
At the start of each cycle
CRP, beta2 
microglobulin
X
X
At the start of each cycle
Pregnancy Test
X10
At the start of cycles 510, 910, 1310
X10
X11
Chest X-ray
X
12-lead ECG
X12
X12
X12
X12
X12
At the start of each cycle12
X12
LVEF and valves 
assessment (ECHO)
X13
At the start of cycles 413, 913
X13
Extramedullary 
Plasmacytoma Imaging
X14
At the start of cycles 514, 914, 1314
X14
BM Aspirate (see below for each test required within procedure):
Disease 
assessment
X15
At the time of Complete Response
BCMA assessment 
and PD (flow)
X16
X16, 18
FISH testing
X17
BM biopsy for disease
assessment 
X19
At the time of CR (disease 
assessment only)
Serum (soluble BCMA)
X20
X20
Predose at the start of each cycle
X
Serum 
(cytokines/chemokines)
X21
X21
Predose and EOI on D1 of each 
cycle
X
Serum (anti-drug-
antibodies)
X22
X22
At the start of cycles 322, 622, 922, 
1222 and 1622
X
Plasma-cfDNA
X
X
Peripheral blood (flow 
for TBNK and 
intracellular cytokine 
testing)
X23
X
X23
At the start of each cycle23
X23
Sparse PK (blood)
X24
X24
C3D124 and C5D124 only
X25
Genetics sample
X26


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Time and Events Table for Full Study (Cycle = 21 days)
Study Assessments1
Screen2
Day 1 
C1
Day 8 
C1
Day 15 
C1
Day 1 C2
D1 of C3-C16
End of 
Study 
Treatment34
Monthly 
Follow 
up35
Premedication if 
needed
X
X
X
GSK2857916  
administration
X27
X27
X27
Steroid eye drops
X28
X28
X28
Adverse Events
Continuous
Concomitant 
Medications
X
Continuous
e-Diary
X
X
X
X
X30
X30
X
OSDI
X31
X31
NEI-VFQ-25
X31
X31
Exit Interview
X32
Follow-up Interview
X33
Survival Status
X29
Subsequent Treatment
X29
1.
Assessments scheduled on days of dosing should be done prior to drug administration, unless otherwise specified.  All other assessments can be done 3 days unless otherwise 
specified
2.
All Screening assessments must be performed within 14 days prior to first dose unless otherwise specified. Informed Consent must be signed before any study-specific 
assessments are performed.
3.
Screening examination to include BCVA (best-corrected visual acuity), slit lamp examination (with special focus on cornea), intraocular pressure, and dilated fundoscopic
examination may be performed within 21 days prior to first dose.
4.
On-study exams, to include BCVA (best-corrected visual acuity) and slit lamp examination (with special focus on cornea); window for exams is up to 3 days prior to dosing. In the 
event that a subject has a dose delay due to a non-ocular toxicity and an ocular exam has been performed for that cycle, a repeat ocular exam 3 days prior to dosing may be 
omitted if the participant did not have corneal signs on the previous exam and does not have any new corneal symptoms.
5.
On initial (first infusion) dosing day, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +10 minutes, +30 minutes (15 min) after SOI, EOI, and 1 hour post 
EOI.  On subsequent dosing days, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +30 minutes after SOI, and EOI.  On days where vital sign 
timepoints align with PK sampling timepoints, vital signs should be assessed prior to PK samples being drawn.
6.
If completed within 72 hrs prior to the first dose, this assessment need not be repeated on Day 1 of Cycle 1.  Refer to Table 15 for a comprehensive list of lab tests.  
7.
Troponin will be measured at the local (troponin I or T) and central (troponin I) lab.  
8.
CK-MB at the local lab or if not available by a central laboratory. 
9.
BNP to be measured locally, or if not available by a central laboratory, at screening; if cardiac workup is required due to safety concerns during the study, BNP should be 
measured.


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10. Perform only in women of child-bearing potential.  A serum pregnancy test should be performed at screening, and subsequent pregnancy tests may be either serum or urine.
11. Final pregnancy test (serum or urine) must be performed in women of childbearing potential 60 days after last study treatment.
12. ECGs to be performed in triplicate.  On dosing days, ECG to be performed at predose (within 30 minutes prior to SOI) and EOI.  At screening, on interim visits (C1D8 and C1D15) 
and End of Study, obtain a single ECG measurement. On days where ECG timepoints align with PK sampling timepoints, ECGs should be performed prior to PK samples 
being drawn (PK sample should be taken at the exact nominal time; refer to footnote 24)
13. At Screening, LVEF may be performed within 30 days prior to first dose. All ECHOs indicated on dosing days may be performed up to 5 days before dosing. ECHOs to be done 
locally and sent to GSK for central imaging storage.
14. May be performed up to 21 days prior to C1D1 as screening value.  Needs to be performed with the same method throughout the study as was done at baseline (i.e. if PET scan 
was used as baseline, subject needs to be followed by PET scans).  Selected target lesion needs to be measured and followed over time.
15. Samples from within 14 days prior to first dose are acceptable.
16. Sample(s) collected for analysis at central lab. The same sample will be used for BCMA (flow) and PD. On D8 only postdose PD assessment will be performed, if applicable (refer 
to footnote 18).
17. 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.
18. Additional samples may be collected in some subjects (up to 6) for further exploration of PD.
19. Archival tissue from up to 60 days prior to study is acceptable.
20. Collect sBCMA at C1D1 predose (within 30 minutes prior to SOI) and at EOI (5 minutes), C2D1 at predose (within 30 minutes prior to SOI) and at EOI (+- 5 minutes).
21. Collect cytokines at predose (within 30 minutes prior to SOI) and EOI (5 min) (even when infusion is interrupted or halted) to assess allergic reaction
22. All ADA samples will be collected prior to each infusion
23. Flow cytometry performed central laboratory.
24. PK samples to be taken for both GSK2587916 and cys-mcMMAF measurement on C1D1, C2D1, C3D1, and C5D1 at predose (within 30 minutes prior to SOI) and at EOI (just 
before EOI).
25. Collect 1 PK sample at each subject’s final visit.
26. Informed consent for optional genetics research should be obtained before collecting a sample.
27. Study drug administration 3 day window only.
28. Prophylaxis with prednisolone phosphate 1% or dexamethasone 0.1% 1 drop QID x 4 days starting 1 day prior to treatment
29. All participants should be followed for survival for 1 year from last subject last dose. and whether subsequent treatment for disease was given.  Subject does not need to come in 
for visit. Participants who have completed treatment or the 3 month follow up visit (end of study) prior to amendment 5 will be reconsented for further follow up and survival status.
30. e-Diary to be completed at screening, then Days 1-7, 8, 15 of each treatment cycle. Upon implementation of the e-Diary, these assessments will be required.
31. OSDI and NEI-VFQ-25 to be administered during end of study treatment visit.  Additional assessments for subjects who are experiencing corneal symptoms to be completed via 
telephone on a monthly basis for up to 1 year, or until resolution of symptoms (whichever comes first) during the follow-up period. 
32. Exit interview to be performed within 21 days of end of study visit
33. Optional follow-up telephone interview to explore visual symptoms and changes in symptoms and related impacts following treatment discontinuation be performed at least 6 
months following the End of Study Treatment visit.  This interview would only be for those subjects who experienced corneal symptoms during treatment and consent to 
participate.
34. End of treatment visit should be performed within 30 days (+7 days) after the last dose or prior to the start of new anti-cancer treatment, whichever is earlier. In cases where more 
than 30 days (+7 days) have elapsed from the date of the subject’s last dose due to dosing delays and a subsequent decision to take the subject off treatment, the end of study 
treatment visit should be scheduled as soon as possible to allow the final assessments to be performed at the earliest date.


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35. Participants with corneal signs or symptoms at the end of study treatment visit should be monitored by ophthalmic exam once a month after the last study dose until deemed 
clinically stable by an eye care professional complete resolution or for 12 months (whichever comes first). Corneal exams to include BCVA and slit lamp examination (with special 
focus on cornea). Participants who have completed treatment or the 3 month follow up visit (end of study) will be reconsented for additional ophthalmology follow up.
Abbreviations:
ADA = Antibody Drug Antibody; ALP = alkaline phosphatase; BCVA = best corrected visual acuity; BNP = B-type natriuretic peptide; C1D1 = Cycle 1 Day 1, etc.; cfDNA = 
Circulating free DNA; CK = creatinine kinase;  CRP = C-reactive protein; EM = extramedullary;  EOI = End of Infusion; FLC = free light chain; PD = Pharmacodynamics; PK = 
Pharmacokinetics; QID = 4 times a day; SOI = start of infusion; SPEP = serum protein electrophoresis; UPEP = urine protein electrophoresis


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7.1.2.2.
Dose Expansion Weekly Dosing Schedule for Multiple Myeloma
Time and Events Table for Full Study (Cycle = 28 days)
Study Assessments1
Screen2
Day 1 
C1
Day 8 C1
Day 15 
C1
Day 1 
C2
Day 15 
C2
D1 of C3-C16
End of Study 
Treatment
3-Month
Off-study 
Follow-up
Informed Consent
X
Baseline Demographics
X
Medical History
X
Physical Exam
X
X
X
At the start of each cycle
X
Ocular Exam
X3
X4
At the start of each cycle4
X4
ECOG Performance 
Status
X
X
At the start of each cycle
X
Vital Signs (BP, HR, Body 
Temperature)
X
X5
X5
X5
X5
At the start of each cycle5
X
Weight and Height
X
Weight 
only
Weight 
only
Weight only - At the start of each cycle
Weight
Hematology
X
X6
X
X
X
At the start of each cycle
X
Clinical chemistry
X
X6
X
X
X
X
At the start of each cycle
X
Urine Dipstick
X
X6
X
At the start of each cycle
X
INR, PTT 
X
X6
X
X
X
At the start of each cycle
HBV/HCV tests
X
CK-MB , Troponin 
X7
X7
X7
At the start of each cycle7
X7
BNP
X8
UPEP and urine 
immunofixation
X
X
At the start of each cycle
SPEP and serum 
immunofixation and Serum 
M-protein Calculation
X
X
At the start of each cycle
Kappa, lambda free LC, 
FLC ratio
X
X
At the start of each cycle
24 hr urine protein and 
albumin 
X
X
At the start of each cycle
IgG, IgM, IgA
X
X
At the start of each cycle


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Time and Events Table for Full Study (Cycle = 28 days)
Study Assessments1
Screen2
Day 1 
C1
Day 8 C1
Day 15 
C1
Day 1 
C2
Day 15 
C2
D1 of C3-C16
End of Study 
Treatment
3-Month
Off-study 
Follow-up
CRP, beta2 microglobulin
X
X
X
At the start of each cycle
Pregnancy Test 
X9
At the start of cycles 59, 99, 139
X9
X10
Chest X-ray
X
12-lead ECG
X11
X11
X11
X11
X11
At the start of each cycle11
X11
LVEF and valves 
assessment (ECHO)
X12
At the start of cycles 412, 912
X12
Extramedullary 
Plasmacytoma Imaging
X13
At the start of cycles 513, 913, 1313
X13
BM Aspirate (see below for each test required within procedure):
Disease assessment 
X14
At the time of Complete Response
BCMA assessment 
and PD (flow)
X15
X15, 17
FISH testing 
X16
BM biopsy for disease 
assessment 
X18
At the time of Complete Response (disease 
assessment only)
Serum (soluble BCMA) 
X19
X19
X19
X19
Predose at the start of each cycle
X
Serum 
(cytokines/chemokines)
X20
X20
X20
X20
Predose and EOI on D1 of each cycle
X
Serum (anti-drug-
antibodies)
X21
X21
X21
At the start of cycles 321, 621, 921, 1221 and 1621
X
Plasma-cfDNA 
X
X
X 
Peripheral blood (flow for 
TBNK and intracellular 
cytokine testing)
X15
X
X15
At the start of each cycle15
X15
Sparse PK (blood) 
X22
X22
X22
X22
X22
C3D122, C3D1522, and C5D122 only
X23
Genetics sample
X24
Premedication if needed
X
X
X
X
X
Each dosing week
GSK2857916  
administration
X25
X25
X25
X25
X25
Each dosing week25
Steroid eye drops
X26
X26
X26
X26
X26
Each dosing week26
Adverse Events
Continuous


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Time and Events Table for Full Study (Cycle = 28 days)
Study Assessments1
Screen2
Day 1 
C1
Day 8 C1
Day 15 
C1
Day 1 
C2
Day 15 
C2
D1 of C3-C16
End of Study 
Treatment
3-Month
Off-study 
Follow-up
Concomitant Medications
X
Continuous
e-Diary
X
X
X
X
X
X28
X
Exit Interview
X29
Survival Status
X27
Subsequent Treatment
X27
1.
Assessments scheduled on days of dosing should be done prior to drug administration, unless otherwise specified. All other assessments can be done 3 days unless otherwise 
specified 
2.
All Screening assessments must be performed within 14 days prior to first dose unless otherwise specified. Informed Consent must be signed before any study-specific 
assessments are performed.
3.
Screening examination to include BCVA (best-corrected visual acuity), slit lamp examination (with special focus on cornea), intraocular pressure, and dilated fundoscopic
examination may be performed within 21 days prior to first dose.
4.
On-study exams, to include BCVA (best-corrected visual acuity) and slit lamp examination (with special focus on cornea); window for exams is up to 3 days prior to dosing.
5.
On initial (first infusion) dosing day, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +10 minutes and +30 minutes (5 min) after SOI, EOI, and 1 hour 
post EOI.  On subsequent dosing days, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +30 minutes after SOI, and EOI.  On days where vital sign 
timepoints align with PK sampling timepoints, vital signs should be assessed prior to PK samples being drawn.  
6.
If completed within 72 hrs prior to the first dose, this assessment need not be repeated on Day 1 of Cycle 1.  Refer to Table 15 for comprehensive list of lab tests.   
7.
Troponin will be measured at the local (troponin I or T) and central (troponin I) lab.  CK-MB at the local lab, or if not available by a central laboratory. 
8.
BNP to be measured locally, or if not available by a central laboratory, at screening; if cardiac workup is required due to safety concerns during the study, BNP should be 
measured.
9.
Perform only in women of child-bearing potential.  A serum pregnancy test should be performed at screening, and subsequent pregnancy tests may be either serum or urine
10. Final pregnancy test (serum or urine) must be performed in women of childbearing potential 60 days after last study treatment.
11. ECGs to be performed in triplicate.  On dosing days, ECG to be performed at predose (within 30 minutes prior to SOI) and EOI.  On days where ECG timepoints align with PK 
sampling timepoints, ECGs should be performed prior to PK samples being drawn (PK sample should be taken at the exact nominal time; refer to footnote 22). At 
screening and End of Study, obtain a single ECG measurement.
12. At Screening, LVEF may be performed within 30 days prior to first dose.  All ECHOs indicated on dosing days may be performed up to 7 days before dosing. ECHOs to be done 
locally and sent to GSK for central imaging storage.
13. May be performed up to 21 days prior to C1D1 as screening value.  Needs to be performed with the same method throughout the study as was done at baseline (i.e. if PET scan 
was used as baseline, subject needs to be followed by PET scans).  Selected target lesion needs to be measured and followed over time.
14. Samples from within 14 days prior to first dose are acceptable.
15. Sample(s) collected for analysis at central lab. The same sample collected on Day 1 of cycle1 prior to dosing will be used for BCMA (flow) and PD (refer to footnote 17).


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16. 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.
17. Additional samples may be collected from 6 subjects in the MM cohort.  Collect sample prior to dosing.
18. Archival tissue from up to 60 days prior to study is acceptable
19. A single sBCMA sample will be collected at C1D1 predose (within 30 minutes prior to SOI) unless otherwise specified.  On C1D15 and C2D1 collect samples at predose (within 30 
minutes prior to SOI) and at EOI (5 minutes).  
20. Collect cytokines at predose (within 30 minutes prior to SOI) and EOI (5 min) (even when infusion is interrupted or halted) to assess allergic reaction
21. All ADA samples will be collected prior to each infusion
22. PK samples to be taken for both GSK2857916 and cys-mcMMAF measurement at C1D1 predose (within 30 minutes prior to SOI), EOI (just before EOI), 1 hour post EOI (5 min), 
and 3 hours post EOI (5 min); predose (within 30 minutes prior to SOI) and EOI (just before EOI) on C1D8, C1D15, C2D1, C2D15, C3D1, C3D15, and C5D1
23. Collect 1 PK sample at each subject’s final visit
24. Informed consent for optional genetics research should be obtained before collecting a sample.
25. Study drug administration 1 day window only
26. Prophylaxis with prednisolone phosphate 1% or dexamethasone 0.1% 1 drop QID x 4 days starting 1 day prior to treatment
27. Record subject’s survival status and whether subsequent treatment for disease was given.  Subject does not need to come in for visit.
28. e-Diary to be completed at screening, then Days 1-7, 8, 15 of each treatment cycle. Upon implementation of the e-Diary, these assessments will be required.
29. 29.Exit interview to be performed within 14 days of end of study visit
Abbreviations:
ADA = Antibody Drug Antibody; ALP = alkaline phosphatase; BCVA = best corrected visual acuity; BNP = B-type natriuretic peptide; C1D1 = Cycle 1 Day 1, etc.; cfDNA = 
Circulating free DNA; CK = creatinine kinase;  CRP = C-reactive protein; EM = extramedullary;  EOI = End of Infusion; FLC = free light chain; PD = Pharmacodynamics; PK = 
Pharmacokinetics; QID = 4 times a day; SOI = start of infusion; SPEP = serum protein electrophoresis; UPEP = urine protein electrophoresis


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7.1.2.3.
Dose Expansion Every 3 Weeks Dosing Schedule for Lymphomas
Study Assessments1
Screen2
Day 1 C1
Day 8 C1
Day 15 C1
Day 1 C2
D1 of C3-C16
End of 
Study 
Treatment26
Monthly 
Follow 
up27
Informed Consent
X
Baseline Demographics
X
Medical History
X
Physical Exam
X
X
X
At the start of each cycle
X
Ocular Exam
X3
X4
At the start of each cycle4
X4
X27
ECOG Performance 
Status
X
X
At the start of each cycle
X
Vital Signs (BP, HR, 
Body Temperature)
X
X5
X
X
X5
At the start of each cycle5
X
Weight and Height
X
Weight only
Weight only
Weight only - At the start of 
each cycle
Weight only
Hematology
X
X6
X
X
X
At the start of each cycle
X
Clinical chemistry
X
X6
X
X
X
At the start of each cycle
X
Urine Dipstick
X
X6
X
At the start of each cycle
X
INR, PTT
X
X6
X
X
X
At the start of each cycle
HBV/HCV tests
X
CK-MB, Troponin 
X7,8
X7,8
X7,8
At the start of each cycle7
X7,8
BNP
X9
24 hr urine protein and 
albumin 
X
X
At the start of each cycle
IgG, IgM, IgA
X
X
At the start of each cycle
CRP, beta2 
microglobulin
X
X
At the start of each cycle
Pregnancy Test 
X10
At the start of cycles 510, 910, 
1310
X10
X11
Chest X-ray
X
12-lead ECG
X12
X12
X12
X12
X12
At the start of each cycle12
X12
LVEF and valves 
assessment (ECHO)
X13
At the start of cycles 413, 913
X13
Serum (soluble BCMA) 
X14
X14


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Study Assessments1
Screen2
Day 1 C1
Day 8 C1
Day 15 C1
Day 1 C2
D1 of C3-C16
End of 
Study 
Treatment26
Monthly 
Follow 
up27
Serum 
(cytokines/chemokines)
X15
X15
Predose and EOI on D1 of 
each cycle
X
Serum (anti-drug-
antibodies)
X16
X16
At the start of cycles 316, 616, 
916, 1216 and 1616
X
Plasma-cfDNA 
X
X 
Peripheral blood (flow 
for TBNK and 
intracellular cytokine 
testing)
X17
X17
X17
At the start of each cycle17
X17
Sparse PK (blood)
X18
X18
C3D118 and C5D118
X19
Genetics sample
X20
CT Scan/PET Scan for 
disease assessments 
X21
At the start of cycles 4, 7, 10, 
13, and 16
Premedication if needed
X
X
At the start of each cycle
GSK2857916  
administration
X22
X22
X22
Steroid eye drops
X23
X23
At the start of each cycle23
Tumor biopsy for BCMA 
expression
X24
Adverse Events
Continuous
Concomitant 
Medications
X
Continuous
Survival Status
X25
Subsequent Treatment
X25
1.
Assessments scheduled on days of dosing should be done prior to drug administration, unless otherwise specified.  All other assessments can be done 3 days of scheduled 
occurrence unless otherwise specified.
2.
All Screening assessments must be performed within 14 days prior to first dose unless otherwise specified. Informed Consent must be signed before any study-specific 
assessments are performed.
3.
Screening examination to include BCVA (best-corrected visual acuity), slit lamp examination (with special focus on cornea), intraocular pressure, and dilated fundoscopic 
examination may be performed within 21 days prior to first dose.
4.
On-study exams to include BCVA (best-corrected visual acuity) and slit lamp examination (with special focus on cornea); window for exams is up to 3 days prior to dosing. In the 
event that a subject has a dose delay due to a non-ocular toxicity and an ocular exam has been performed for that cycle, a repeat ocular exam 3 days prior to dosing may be 
omitted if the participant did not have corneal signs on the previous exam and does not have any new corneal symptoms.


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5.
On initial (first infusion) dosing day, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +10 minutes, +30 minutes (±15 min) after SOI, EOI, and 1 hour post 
EOI.  On subsequent dosing days, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +30 minutes after SOI, and EOI.  On days where vital sign 
timepoints align with PK sampling timepoints, vital signs should be assessed prior to PK samples being drawn.  
6.
If completed within 72 hrs prior to the first dose, this assessment need not be repeated on Day 1 of Cycle 1.  Refer to Table 15 for a comprehensive list of lab tests.  
7.
Troponin will be measured at the local (troponin I or T) and central (troponin I) lab.  
8.
CK-MB at the local lab, or if not available by a central laboratory. 
9.
BNP to be measured locally at screening; if cardiac workup is required due to safety concerns during the study, BNP should be measured.
10. Perform only in women of child-bearing potential.  A serum pregnancy test should be performed at screening, and subsequent pregnancy tests may be either serum or urine.
11. Final pregnancy test (serum or urine) must be performed in women of childbearing potential 60 days after last study treatment.
12. On dosing days, triplicate ECGs to be performed at predose (within 30 minutes prior to SOI) and EOI.  On days where ECG timepoints align with PK sampling timepoints, 
ECGs should be performed prior to PK samples being drawn (PK sample should be taken at the exact nominal time; refer to footnote 18).  At screening, on interim visits 
(C1D8 and C1D15) and End of Study, obtain a single ECG measurement.
13. At Screening, LVEF may be performed within 30 days prior to first dose.  All ECHOs indicated on dosing days may be performed up to 5 days. ECHOs to be done locally and sent 
to GSK for central imaging storage.
14. A single sBCMA sample will be collected at C1D1 predose (within 30 minutes prior to SOI).  On C2D1 sBCMA will be collected at predose (within 30 minutes prior to SOI) and at 
EOI (5 minutes).
15. Collect cytokines at predose (within 30 minutes prior to SOI) and EOI (5 min) (even when infusion is interrupted or halted) to assess allergic reaction.
16. All ADA samples will be collected prior to each infusion.
17. Sample(s) collected for analysis by central lab.
18. PK samples to be taken for both GSK2587916 and cys-mcMMAF measurement on C1D1 at pre-dose (within 30 minutes prior to SOI), at EOI (just before EOI), 1 h after EOI (5 
min), 3 h after EOI (5 min); C2D1, C3D1, and C5D1 at pre-dose (within 30 minutes prior to SOI) and at EOI (just before EOI).
19. Collect 1 PK sample at each subject’s final visit.
20. Informed consent for optional genetics research should be obtained before collecting a sample.
21. CT/PET or CT scans from within 21 days prior to first dose are acceptable. CT scans are acceptable at all restaging assessments unless CR is suspected, in which case a 
PET/CT scan will be obtained to confirm CR.
22. Study drug administration 3 day window only.
23. Prophylaxis with prednisolone phosphate 1% or dexamethasone 0.1% 1 drops QID x 4 days starting 1 day prior to treatment.
24. Archived or fresh tissue required for BCMA testing.  Refer to Section 5.2.1 Inclusion Criterion #4 for eligibility criteria. 
25. Record subject’s survival status until last subject completes or discontinues treatment and whether subsequent treatment for disease was given.  Subject does not need to come 
in for visit.
26. End of treatment visit should be performed within 30 days (+7 days) after the last dose or prior to the start of new anti-cancer treatment, whichever is earlier. In cases where more 
than 30 days (+7 days) have elapsed from the date of the subject’s last dose due to dosing delays and a subsequent decision to take the subject off treatment, the end of study 
treatment visit should be scheduled as soon as possible to allow the final assessments to be performed at the earliest date.
27. All participants should be followed for survival for 1 year from last dose. Participants with corneal signs or symptoms at the end of study treatment visit should be monitored by 
ophthalmic exam every month after the last study dose until deemed clinically stable by an eye care professional or for 12 months (whichever comes first). Corneal exams to 
include BCVA and slit lamp examination (with special focus on cornea).


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Abbreviations:
ADA = Antibody Drug Antibody; ALP = alkaline phosphatase; BCVA = best corrected visual acuity; BNP = B-type natriuretic peptide; C1D1 = Cycle 1 Day 1, etc.; cfDNA = 
Circulating free DNA; CK = creatine kinase; CRP = C-reactive protein; EOI = End of Infusion; PD = Pharmacodynamics; PK = Pharmacokinetics; QID = 4 times a day; SOI = start 
of infusion


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7.1.2.4.
Dose Expansion Weekly Dosing Schedule for Lymphomas
Time and Events Table for Full Study (Cycle = 28 days)
Study Assessments1
Screen2
Day 1 
C1
Day 8 C1
Day 15 
C1
Day 1 
C2
Day 15 
C2
D1 of C3-C16
End of Study 
Treatment
3-Month 
Off-study 
Follow-up
Informed Consent
X
Baseline Demographics
X
Medical History
X
Physical Exam
X
X
X
At the start of each cycle
X
Ocular Exam
X3
X4
At the start of each cycle4
X4
ECOG Performance 
Status
X
X
At the start of each cycle
X
Vital Signs (BP, HR, Body 
Temperature)
X
X5
X5
X5
X5
At the start of each cycle5
X
Weight and Height
X
Weight 
only
Weight 
only
Weight only - At the start of each cycle
Weight
Hematology
X
X6
X
X
X
At the start of each cycle
X
Clinical chemistry
X
X6
X
X
X
X
At the start of each cycle
X
Urine Dipstick
X
X6
X
At the start of each cycle
X
INR, PTT 
X
X6
X
X
X
At the start of each cycle
HBV/HCV tests
X
CK-MB , Troponin 
X7
X7
X7
At the start of each cycle7
X7
BNP
X8
24 hr urine protein and 
albumin 
X
X
At the start of each cycle
IgG, IgM, IgA
X
X
At the start of every other  cycle
CRP, beta2 microglobulin
X
X
At the start of each cycle
Pregnancy Test 
X9
At the start of cycles 59, 99, 139
X9
X10
Chest X-ray
X
12-lead ECG
X11
X11
X11
X11
X11
At the start of each cycle11
X11
LVEF and valves 
assessment (ECHO)
X12
At the start of cycles 412, 912
X12


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Time and Events Table for Full Study (Cycle = 28 days)
Study Assessments1
Screen2
Day 1 
C1
Day 8 C1
Day 15 
C1
Day 1 
C2
Day 15 
C2
D1 of C3-C16
End of Study 
Treatment
3-Month 
Off-study 
Follow-up
Serum (soluble BCMA) 
X13
X13
X13
X13
X13
Serum 
(cytokines/chemokines)
X14
X14
X14
X14
Predose and EOI on D1 of each cycle
X
Serum (anti-drug-
antibodies)
X15
X15
X15
At the start of cycles 315, 615, 915, 1215 and 
1615
X
Plasma-cfDNA 
X
X 
Peripheral blood (flow for 
TBNK)
X16
X16
X16
At the start of each cycle16
X16
Sparse PK (blood) 
X17
X17
X17
X17
X17
C3D117, C3D1517 and C5D117 only
X18
Genetics sample
X19
CT/PET Scan for disease 
assessments 
X20
At the start of Cycles 3, 5, 7, 9, 11, 13, and 
16
Premedication if needed
X
X
X
X24
X
Each dosing week
GSK2857916  
administration
X21
X21
X21
X21, 24
X
Each dosing week21
Steroid eye drops
X22
X22
X22
X22, 24
X22
Each dosing week22
Tumor biopsy for BCMA 
expression
X23
Adverse Events
Continuous
Concomitant Medications
X
Continuous
Survival Status
X25
Subsequent Treatment
X25
1.
Assessments scheduled on days of dosing should be done prior to drug administration, unless otherwise specified.  All other assessments can be done 3 days unless otherwise 
specified
2.
All Screening assessments must be performed within 14 days prior to first dose unless otherwise specified. Informed Consent must be signed before any study-specific 
assessments are performed.
3.
Screening examination to include BCVA (best-corrected visual acuity), slit lamp examination (with special focus on cornea), intraocular pressure, and dilated fundoscopic 
examination may be performed within 21 days prior to first dose.
4.
On-study exams, to include BCVA (best-corrected visual acuity) and slit lamp examination (with special focus on cornea); window for exams is up to 3 days prior to dosing. In the 
event that a subject has a dose delay due to a non-ocular toxicity and an ocular exam has been performed for that cycle, a repeat ocular exam 3 days prior to dosing may be 
omitted if the participant did not have corneal signs on the previous exam and does not have any new corneal symptoms.


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5.
On initial (first infusion) dosing day, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +10 minutes and +30 minutes after SOI (5 min), EOI, and 1 hour 
post EOI.  On subsequent dosing days, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +30 minutes after SOI, and EOI.  On days where vital sign 
timepoints align with PK sampling timepoints, vital signs should be assessed prior to PK samples being drawn.  
6.
If completed within 72 hrs prior to the first dose, this assessment need not be repeated on Day 1 of Cycle 1.  Refer to Table 15 for comprehensive list of lab tests.   
7.
Troponin will be measured at the local (troponin I or T) and central (troponin I) lab.  CK-MB at the local lab, or if not available by a central laboratory. 
8.
BNP to be measured locally, or if not available by a central laboratory, at screening; if cardiac workup is required due to safety concerns during the study, BNP should be 
measured.
9.
Perform only in women of child-bearing potential.  A serum pregnancy test should be performed at screening, and subsequent pregnancy tests may be either serum or urine
10. Final pregnancy test (serum or urine) must be performed in women of childbearing potential 60 days after last study treatment.
11. On dosing days, perform triplicate ECGs at predose (within 30 minutes prior to SOI) and EOI.  On days where ECG timepoints align with PK sampling timepoints, ECGs 
should be performed prior to PK samples being drawn (PK sample should be taken at the exact nominal time; refer to footnote 17).  At screening and End of Study, 
obtain a single ECG measurement.
12. At Screening, LVEF may be performed within 30 days prior to first dose. All ECHOs indicated on dosing days may be performed up to 7 days before dosing. ECHOs to be done 
locally and sent to GSK for central imaging storage.
13. A single sample for sBCMA will be collected at C1D8 predose, and at the End of Study visit.  sBCMA samples will also be collected on C1D1 at predose (within 30 minutes prior to 
SOI) and EOI (5 minutes).  On C1D15 and C2D1 collect at predose (within 30 minutes prior to SOI) and EOI (5 minutes)
14. Collect cytokines at predose (within 30 minutes prior to SOI) and EOI (5 min) (even when infusion is interrupted or halted) to assess allergic reaction.
15. All ADA samples will be collected prior to each infusion.
16. Sample(s) collected for analysis by central lab.
17. PK samples to be taken for both GSK2857916 and cys-mcMMAF measurement at C1D1 predose (within 30 minutes prior to SOI), EOI (just before EOI), 1 hour post EOI (5 min), 
and 3 hours post EOI (5 min); predose (within 30 minutes prior to SOI) and EOI (just before EOI) on C1D8, C1D15, C2D1, C2D15, C3D1, C3D15, and C5D1.
18. Collect 1 PK sample at each subject’s final visit.
19. Informed consent for optional genetics research should be obtained before collecting a sample.
20. CT/PET scans from within 21 days prior to first dose are acceptable.
21. Study drug administration 1 day window only.
22. Prophylaxis with prednisolone phosphate 1% or dexamethasone 0.1% 1 drops QID x 4 days starting 1 day prior to treatment.
23. Archived or fresh tissue required for BCMA testing.  Refer to Section 5.2.1 Inclusion Criterion #4 for eligibility criteria. 
24. Also applies to C2D8.
25. Record subject’s survival status and whether subsequent treatment for disease was given.  Subject does not need to come in for visit.
Abbreviations:
ADA = Antibody Drug Antibody; ALP = alkaline phosphatase; BCVA = best corrected visual acuity; BNP = B-type natriuretic peptide; C1D1 = Cycle 1 Day 1, etc.; cfDNA = 
Circulating free DNA; CK = creatine kinase; CRP = C-reactive protein; EOI = End of Infusion; PD = Pharmacodynamics; PK = Pharmacokinetics; QID = 4 times a day; SOI = start 
of infusion


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7.2.
Demographic/Medical History and Baseline Assessments
The following demographic parameters will be captured during Screening: date of birth, 
gender, race and ethnicity.
Medical/medication history assessed as related to the eligibility criteria listed in Section 
5.2.
Baseline (Screening) assessments obtained will include:

Complete physical examination, including height (in cm) and weight (in kg).

Vital signs (blood pressure, temperature, pulse rate)

Chest x-ray

Ocular exam

Eastern Cooperative Oncology Group (ECOG) performance status

Clinical laboratory tests outlined in Table 15

Serum beta-human chorionic gonadotropin (-HCG) pregnancy test for female 
subjects of childbearing potential only

12-lead electrocardiogram (ECG)

Echocardiogram (ECHO) 

Imaging studies (extramedullary disease for MM if indicated, or CT/PET scan for
lymphomas)

For MM: BM aspirate for FISH, BCMA (flow cytometry), PD (target engagement 
and caspase 3); BCMA expression (IHC)

For MM: BM biopsy for disease assessment 

For Lymphomas: archival or fresh tissue evaluation for BCMA expression

Review of concomitant medications
Procedures conducted as part of the subject’s routine clinical management (e.g., blood 
count, imaging study) and obtained prior to signing of informed consent may be utilized 
for Screening or baseline purposes provided the procedure meets the protocol-defined 
criteria and has been performed in the timeframe of the study.
7.2.1.
Critical Baseline Assessments
Cardiovascular medical history/risk factors will be assessed at baseline.
7.3.
Safety Evaluations
Planned time points for all safety assessments are provided in the Time and Events 
Tables (Section 7.1).


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7.3.1.
Physical Examinations
At screening and on dosing days, 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 and 
recorded.
During interim visits and at the end of study, a brief physical examination will include 
assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen).
7.3.2.
ECOG Performance Status
The performance status will be assessed using the Eastern Cooperative Oncology Group 
(ECOG) scale (Appendix 6) as specified in the Time and Events Tables (Section 7.1).
7.3.3.
Vital Signs
Vital sign measurements will include systolic and diastolic blood pressure, temperature, 
and pulse rate.  Vital signs should be measured after resting for at least 5 minutes.  Vital 
signs will be measured more frequently if warranted by the clinical condition of the 
subject.  On days where vital signs are measured multiple times, temperature does not 
need to be repeated unless clinically indicated.  
First Infusion:
Monitoring intervals:  Vital signs must be monitored at predose (within 30 minutes prior 
to start of infusion), +10 and +30 minutes post start of infusion, and at the end of 
infusion, and 1 hour post end of infusion.  In general, subjects 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.  
Sentinel subject:  Subject must be monitored for at least 24 hours post first infusion.
Subsequent subjects:  Subjects may be discharged if considered clinically stable and all 
other study procedures have been completed.  
Subsequent Infusions:
Monitoring intervals:  Vital signs must be monitored at predose (within 30 minutes prior 
to start of infusion), +30 minutes post start of infusion, and at the end of infusion. 
Subjects may be discharged after the infusion has been completed if considered clinically 
stable and all other study procedures have been completed.  
In case of infusion related reactions or cytokine storm, monitoring will be performed with 
higher frequency (as clinically indicated).
7.3.4.
Electrocardiogram
Triple 12-lead electrocardiogram (ECGs) will be obtained at designated time points 
specified in the Time and Events Tables (Section 7.1) during the study using an ECG 


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machine that automatically calculates the heart rate and measures PR, QRS, QT, and 
corrected QT (QTc) intervals.  At each assessment a 12-lead ECG will be performed by 
qualified personnel at the site after the subject has at least a 5 minute rest.  
The QT interval should be corrected for heart rate by Fridericia’s formula (QTcF).  Refer 
to Section 3.9.2 for QTc withdrawal criteria.  Refer to the Study Procedures Manual 
(SPM) for details regarding ECG procedures.
7.3.5.
Echocardiogram
Echocardiograms (ECHOs) will be performed at baseline to assess cardiac ejection 
fraction and cardiac valve morphology for the purpose of study eligibility, as specified in 
the Time and Events Tables (Section 7.1).  Additional ECHO assessments will be 
performed at specified timepoints indicated in the Time and Events Tables (Section 7.1) 
or if clinically warranted.  The evaluation of the echocardiographer should include an 
evaluation for left ventricular ejection fraction (LVEF) and both right and left-sided 
valvular lesions.
Copies of all ECHOs performed on subjects will be stored in a central location if further 
evaluation is warranted. 
7.3.6.
Ocular Exam
An ocular exam to include BCVA (best-corrected visual acquity), slit lamp examination 
(with special focus on the cornea), intraocular pressure, and dilated funduscopic 
examination will be conducted for all subjects at screening. Additional exams will be 
performed as specified in the Time and Events Tables (Section 7.1) during the treatment 
period and at monthly follow-up visits as clinically indicated.
7.3.7.
Laboratory Assessments
All protocol required laboratory assessments, as defined in (Table 15), should be 
performed according to the Time and Events Tables (Section 7.1).  Details for the 
preparation and shipment of samples will be provided in the SPM.
Prior to administration of the first dose of study treatment, results of laboratory 
assessments should be reviewed.  Any laboratory test with a value outside the normal 
range may be repeated (prior to the first dose) at the discretion of the investigator.
If additional non-protocol specified laboratory assessments are performed at the 
institution’s local laboratory and result in a change in patient management or are 
considered clinical significant by the Investigator (for example SAE or AE or dose 
modification) the results must be recorded in the subject’s CRF. Refer to the SPM for 
appropriate processing and handling of samples to avoid duplicate and/or additional 
blood draws. 
All laboratory tests with values that are significantly abnormal during participation in the 
study or within 30 days after the last dose of study treatment should be repeated until the 
values return to normal or baseline.  If such values do not return to normal within a 
period judged reasonable by the investigator, the etiology should be identified and the 
sponsor notified.


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Hematology, clinical chemistry, urinalysis and additional parameters to be tested are 
listed in Table 15:
Table 15
List of Clinical Laboratory Tests
Hematology
Platelet Count
RBC Indices:
Automated WBC Differential:
Red blood cell (RBC) Count
MCV
Neutrophils
White blood cell (WBC) Count 
(absolute) 
MCH
Lymphocytes
Reticulocyte Count
MCHC
Monocytes
Hemoglobin
Eosinophils
Hematocrit
Basophils
Clinical Chemistry
Blood urea nitrogen 
(BUN)
Potassium
Aspartate aminotransferase 
(AST)
Total and direct bilirubin
Creatinine
Chloride
Alanine aminotransferase 
(ALT)
Uric Acid
Glucose
Total carbon 
dioxide (CO2)
Gamma glutamyl transferase 
(GGT)
Albumin
Sodium
Calcium
Alkaline phosphatase
Total Protein
Magnesium
Phosphorous
Creatine kinase (CK)
LDH
Routine Urinalysis
Specific gravity
pH, glucose, protein, blood and ketones by dipstick
Microscopic examination (if blood or protein is abnormal)
24-hour urine protein and albumin
Other screening tests
Hepatitis B (HBsAg)
Hepatitis C (Hep C antibody -- if second generation Hepatitis C antibody positive, a hepatitis C antibody 
Chiron RIBA immunoblot assay or a validated HCV PCR viral test should be reflexively performed on the 
same sample to confirm the result) 
Follicle stimulating hormone (FSH) and estradiol (as needed in women of non-child bearing potential only)
FISH analysis1
Other Laboratory Tests
Troponin
PTT
INR
IgG, IgM, IgA
CK-MB
B-type natriuretic 
peptide
C-reactive protein (CRP)
Beta2 microglobulin
Kappa, lambda free LC, 
FLC ratio
ADA
PGx2
Immunofixation
Serum Protein 
Electrophoresis (SPEP) 
and Serum M-protein 
calculation
Urine Protein 
Electrophoresis (UPEP)
Biomarker Measurements
BCMA/sBCMA
Caspase 3
Serum 
cytokines/chemokines
cfDNA
1. FISH testing at least for: t(4;14), t(14/16), 17p13del.  Biopsy samples from within 60 days prior to first dose are 
acceptable.
2.  Samples to be collected from subjects in expansion cohorts only.


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7.3.8.
Pregnancy Testing and Reporting
The need for a screening pregnancy test depends on whether a female subject is of 
childbearing potential or non-childbearing potential.
If a female subject is of childbearing potential, she must have a serum -HCG pregnancy 
test performed within 14 days prior to the first dose of study treatment.  Subjects with 
positive pregnancy test result must be excluded from the study.  Subjects with negative 
pregnancy test result must agree to use an effective contraception method as described 
below during the study until 60 days following the last dose of study treatment(s).
Any pregnancy that occurs during study participation must be reported using a clinical 
trial pregnancy form.  To ensure subject safety, each pregnancy must be reported to GSK 
within 2 weeks of learning of its occurrence.  The pregnancy must be followed up to 
determine outcome (including premature termination) and status of mother and child.  
Pregnancy complications and elective terminations for medical reasons must be reported 
as an adverse event (AE) or serious adverse event (SAE).  Spontaneous abortions must be 
reported as an SAE.
Any SAE occurring in association with a pregnancy brought to the investigator’s 
attention after the subject has completed the study and considered by the investigator as 
possibly related to the study treatment, must be promptly reported to GSK.
In addition, the investigator must attempt to collect pregnancy information on any female 
partners of male study subjects who become pregnant while the subject is enrolled in the 
study.  Pregnancy information must be reported to GSK as described above.
7.3.9.
Immunogenicity
Serum samples for determination of anti-GSK2857916 antibodies will be taken from all 
subjects in this study at the time-points specified in the Time and Events Tables in 
Section 7.1.  Timing of the assessments may be adjusted based on emerging data.  Details 
of sample preparation, storage and analysis will be provided in the SPM.
Samples will be analyzed for the presence of anti-GSK2857916 antibodies by a validated 
electrochemiluminescent immunoassay. All samples will be tested by a screening assay,
and positive samples will be further characterized for specificity and antibody titers. 
7.3.10.
Visual Functioning Questionnaires
The impact of potential ocular toxicity on function and health-related quality of life will 
be assessed with the use of 2 visual function questionnaires: the National Eye Institute 
Visual Functioning Questionnaire-25 (NEI VFQ-25), and the Ocular Surface Disease 
Index (OSDI).  Subjects will complete the self-administered versions of these two 
assessments during their End of Study Treatment visit.  Subjects who are unable to 
complete the questionnaire on their own due to blurry vision, and require assistance can 
have the questionnaire read to them by an interviewer.  If the questionnaires are 


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administrated by an Interviewer, then the questionnaire should be read to the subjects 
verbatim, and subject responses should be recorded directly without any interpretation.  
Subjects who continue to experience visual symptoms after discontinuation of study 
treatment will complete additional interviewer-administered assessments via telephone on 
a monthly basis for up to 1 year during the Follow-up period or until the resolution of 
their visual symptoms, whichever comes first.
7.3.10.1.
National Eye Institute Visual Functioning Questionnaire-25
The NEI-VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 
vision-related constructs, plus an additional single-item general health rating question 
[Mangione, 2001].  The NEIVFQ-25 generates the following vision-targeted sub-scales:  
global vision rating, difficulty with near vision activities; difficulty with distance vision 
activities; limitations in social functioning due to vision; role limitations due to vision; 
dependency on others due to vision; mental health symptoms due to vision; driving 
difficulties; limitations with peripheral vision, limitations with color vision; and corneal 
pain.  
7.3.10.2.
Ocular Surface Disease Index Questionnaire
The Ocular Surface Disease Index (OSDI) is a 12-item questionnaire designed to assess 
both the frequency of dry eye symptoms and their impact on vision-related functioning 
[Schiffman, 2000]. The OSDI has demonstrated good reliability, validity, sensitivity, and 
specificity, and can be used as a complement to other clinical and subjective measures of 
dry eye disease by providing a quantifiable assessment of dry eye symptom frequency 
and the impact of these symptoms on vision-related functioning.
7.4.
Pharmacokinetics
7.4.1.
Blood Sample Collection for Pharmacokinetics
Blood samples of approximately 5 mL for pharmacokinetic (PK) analysis of 
GSK2857916 (ADC and total antibody) and cys-mcMMAF will be collected at the time 
points indicated in the Time and Events Tables (Section 7.1).  Each PK sample should be 
collected as close as possible to the planned time relative to the dose (i.e., time zero) 
administered to the subject 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 Study Procedures Manual (SPM).  Blood volumes for PK samples are 
outlined in Appendix 10 (Section 16.9).


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7.4.2.
Urine Sample Collection for Pharmacokinetics
Urine samples of approximately 1 mL for pharmacokinetic (PK) analysis of cys-
mcMMAF will be collected from the 24 hour urine collection sample as scheduled in the 
Dose Escalation Time and Events Tables (Section 7.1.1).  The actual date and time of 
each urine sample collection as well as the urine volume collected will be recorded.  In 
addition for qualitative analysis of any metabolite(s) approximately 20mL of control is 
required prior to dosing and a 400mL aliquot as described in the Time and Events 
Schedules (Section 7.1.1)
Details on PK urine sample collection, processing, storage and shipping procedures are 
provided in the Study Procedures Manual (SPM).
7.4.3.
Pharmacokinetic Sample Analysis
Plasma and urine analysis will be performed under the control of GSK Platform 
Technologies and Science (PTS) Drug Metabolism and Pharmacokinetics (DMPK), the 
details of which will be included in the Study Procedures Manual.  Concentrations of 
GSK2857916 (ADC and total antibody) and cys-mcMMAF will be determined in plasma 
and urine (cys-mcMMAF) samples using the currently approved bioanalytical 
methodology.  Raw data will be archived at the bioanalytical site (detailed in the Study 
Procedures Manual).
Once the plasma and urine has been analysed for GSK2857916 (ADC and total antibody) 
and cys-mcMMAF any remaining plasma or urine may be analysed for other compound-
related metabolites and the results reported under a separate GSK PTS-DMPK protocol.
7.5.
Translational Research
7.5.1.
Pharmacodynamics
Blood, bone marrow, and tumor tissue samples will be collected during this study and 
analysed pre and post GSK2857916 at the time points indicated in the Time and Events 
Tables (Section 7.1) to investigate pharmacodynamic response to GSK2857916.  The 
timing of the collections may be adjusted on the basis of emerging PK or 
pharmacodynamic data from this study or other new information in order to ensure 
optimal evaluation of the pharmacodynamic endpoints.  Details on PD blood and bone 
marrow sample collection, processing, storage and shipping procedures are provided in 
the SPM.
Pharmacodynamic markers may include but will not be limited to the following:

Bone marrow analysis of plasma cell BCMA receptor expression by flow cytometry.  
Flow cytometry measurements to include assessment of free and GSK2857916 drug 
bound receptors as well as measures of cell cycle/apoptosis  

Additional soluble measurements to include serum levels of free sBCMA and 
sBCMA complexed to GSK2857916 


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
Whole blood count of mononuclear cells (PBMC) and their activation status and 
intracellular cytokine profile.

Soluble factors, including cytokine/chemokine analysis of serum

RNA/DNA and protein analysis of bone marrow, tumor tissue and blood
7.5.1.1.
BCMA Receptor Occupancy in bone marrow plasma cells
To monitor target engagement, bone marrow aspirates will be evaluated by flow 
cytometry for enumeration of plasma cell numbers of free BCMA receptors and the 
number of GSK2857916 bound receptors, BCMA cell cycle markers, as well as apoptosis 
markers on tumor cells to understand anti-tumor responses.  Flow cytometry markers 
may include but not be limited to:  BCMA, CD138, CD38, CD45, MMAF, CC3, PH3, 
and MPM-2.  
7.5.1.2.
sBCMA Analysis
Target engagement with soluble BCMA will be assessed.  Serum will be collected to 
measure concentrations of free and GSK2857916 bound sBCMA at the timepoints 
specified in the Time and Events Tables (refer to Section 7.1).
7.5.1.3.
Activated TBNK cells
Whole blood will be collected and analyzed for % and absolute counts of monocytes, T, 
B and NK cells as well as the expression of activation markers CD107 and CD69 on 
these cell types.
7.5.1.4.
Cytokine and Chemokine Analysis
Clusters of markers circulating in the blood have been found to correlate with tumor 
pathway activation.  A broad panel of cytokines/chemokines will be evaluated at various 
timepoints as outlined in the Time and Events table (Section 7.1) and correlated with 
clinical outcome to treatment with GSK2857916. In addition to measuring total cytokine 
levels in serum, activated lymphocytes and monocytes producing involved in the 
cytokine production will be determined via intracellular cytokine assay. 
7.5.2.
Subject stratification/predictive biomarkers
BCMA exhibits varied expression across B-cell hematologic malignancies and therefore, 
BCMA expression levels at baseline may be an important predictor of response to 
GSK2857916. To evaluate whether BCMA expression has utility in patient stratification
or selection, malignant plasma cells at baseline will be measured for BCMA expression 
by IHC and/or flow cytometry.  Because BCMA can also be detected in circulation, the 
soluble form (sBCMA) has the potential to serve as a surrogate for cell surface BCMA 
marker expression. This study will correlate subject’s sBCMA levels with cell surface 
expression and clinical response to support future validation of sBCMA as a patient 
selection marker, if data warrant. In addition baseline measurements of peripheral blood 
mononuclear cells and cytokines/chemokines will help inform on subject immune status.


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Blood and bone marrow samples will be collected during this study and may be used for 
the purposes of measuring novel biomarkers to identify factors that may influence 
advanced multiple myeloma, hematological malignancies and/or medically related 
conditions, as well as the biological and clinical responses to GSK2857916.  If relevant, 
this approach may be extended to include the identification of biomarkers associated with 
AEs.
Unless stated otherwise, these investigations may be performed irrespective of whether a 
response to GSK2857916 is observed.
Samples will be collected at the time points indicated in the Time and Events Tables 
Section 7.1.  The timing of the collections may be adjusted on the basis of emerging PK 
or pharmacodynamic data from this study or other new information in order to ensure 
optimal evaluation of the pharmacodynamic endpoints.  Novel candidate biomarkers and 
subsequently discovered biomarkers of the biological response associated with advanced 
multiple myeloma, lymphomas and/or medically related conditions, as well as the 
biological and clinical responses to GSK2857916 may also be evaluated.  These analyses 
may include but not be limited to:

Tumor/plasma cell BCMA receptor expression by flow cytometry and/or IHC.    

Soluble factors, including circulating cfDNA analysis of tumor tissue and plasma and 
cytokine/chemokine analysis of plasma

Additional soluble measurements to include serum levels of free sBCMA 

Activated PBMC count analysis of whole blood and intracellular cytokine assessment

RNA/DNA/gene and protein analysis of tumor tissue
7.5.3.
Tumor Biomarker Analysis
In order to further characterize the subject population biomarkers (e.g. expression of 
genes and proteins) related to the activity of the investigational compound will be 
assessed in baseline tissue and pre and post treatment biopsies as well as cf-DNA 
obtained at disease progression. 
BCMA expression in the plasma cells of bone marrow aspirates or trephines will be 
evaluated at baseline by IHC and/or flow cytometry for plasma cell expression of free 
BCMA receptors.  IHC and flow cytometry markers may include but not be limited to:  
BCMA, Blimp1, CD138, and CD38.  Additionally, bone marrow tumor tissue may be 
evaluated for any DNA /RNA changes correlating with response.
7.5.3.1.
Circulating cell free DNA (cfDNA) analysis
Additionally, bone marrow tumor tissue may be evaluated for any DNA/RNA changes 
correlating with response.  Tumor –specific circulating nucleic acid (cfDNA) levels 
detected in plasma or serum have been found to correlate with increasing tumor burden 
and decline following therapy.  Furthermore, cfDNA in cancer subjects can harbor many 


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genetic alterations (mutations, microsatellite alterations, aberrant methylation), which are 
generally consistent with the tumor.  Thus, tumor-specific circulating cfDNA has the 
potential to be a useful biomarker of therapeutic response as well as offering a less 
invasive blood based technique for identifying and selecting subjects for certain 
treatments.  Given the promise of cfDNA blood based test for subject selection, this test 
will be explored to determine whether mutations in cfDNA correlate with that in the 
tumor tissue from which it is derived.  This test will also be explored to correlate 
increasing cfDNA levels with increasing tumour burden.  
7.6.
Genetics
An important exploratory objective of the clinical study is genetic research.  Participation 
in genetics research is optional but all subjects who are eligible for the clinical study and 
are enrolled into part 2 (expansion cohort) will be given the opportunity to participate.  
Subjects may decline participation without effect on their medical care or care during the 
clinical study.  A separate consent signature is required for genetic research.
Information regarding genetic research is included in Appendix 7.  In approving the 
clinical protocol the IEC/IRB and, where required, the applicable regulatory agency are 
also approving the genetic research described in Appendix 7 unless otherwise indicated.  
Where required by regulatory authorities, approval of the genetic assessments can occur 
after approval is obtained for the rest of the study.  If so, then the written approval will 
clearly indicate approval of the genetic assessments is being deferred and the study, 
except for genetic assessments, can be initiated.  When genetic assessments will not be 
approved, then the approval for the rest of the study will clearly indicate this and 
therefore, genetic assessments will not be conducted.
7.7.
Evaluation of Anti-Cancer Activity
Standard disease assessments for MM will include laboratory tests, bone marrow aspirate 
(cytology, flow cytometry, FLC, etc.) and Bone Marrow biopsy for BCMA expression 
(IHC) during screening and at the time of CR.  Evaluation will be according to the 
International Myeloma Working Group Uniform Response Criteria for Multiple 
Myeloma (Appendix 1).  Disease assessment for subjects with lymphomas will be 
evaluated at screening and every 9 weeks (for subjects on every 3 week dosing schedule) 
or every 8 weeks (for subjects on weekly dosing schedule), and at the end of study.  
Disease assessment for subjects with lymphomas will be according to the Revised 
Response Criteria for Malignant Lymphoma (Appendix 2).

Clinical activity measured as Overall Response Rate (ORR) which is defined as 
follows:

For MM: the percentage of subjects with confirmed stringent complete response 
(sCR), complete response (CR), very good partial response (VGPR), and partial 
response (PR) as assessed by 2011 recommendation of the International 
Myeloma Working Group (IMWG) Panel I (Appendix 1).  Other comparisons of 
interest may be considered (see Section 13.5.2) 


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
For lymphomas: the percentage of subjects with confirmed CR, PR, as described 
in the Revised Response Criteria for Malignant Lymphoma (Appendix 2). 
Disease assessment may include imaging (e.g., computed tomography [CT] scan, 
magnetic resonance imaging [MRI], bone scan, plain radiography) and physical 
examination (as indicated for palpable/superficial lesions). Disease assessment will be 
completed within 4 weeks prior to the first dose of GSK2857916 then every 8 or 9 weeks 
thereafter, and at the final study visit.  See the Time and Events Tables (Section 7.1) for 
the schedule of assessments of anti-cancer activity.  Assessments must be performed on a 
calendar schedule and should not be affected by dose interruptions/delays.  For post-
baseline assessments, a window of 3 days is permitted to allow for flexible scheduling 
with the exception of dose administration days where a window of 3 days for Schedule 
1 (once every 3 weeks) is permitted and 1 day for Schedule 2 (weekly) is permitted.  If 
the last radiographic assessment was more than 8 or 9 weeks prior to the subject’s 
withdrawal from study and progressive disease has not been documented, a disease 
assessment should be obtained at the time of withdrawal from study.
7.8.
Health Outcomes: Quality of Life
7.8.1.
Bone Pain/Fatigue Assessment (eDiary)
The patient reported outcome (PRO) instruments that will be used are the Bone 
Pain/Fatigue Assessment via an e-Diary. In the Part 2 multiple myeloma cohort, the 
implementation of this assessment will occur upon availability of the instruments. 
Bone Pain/Fatigue Assessment: Bone pain burden will be measured by e-Diary consisting 
of certain modified questions from Brief Pain Inventory-Short Form (BPI-SF) which 
assesses pain intensity and the interference of pain with daily life [Atkinson, 2010;
Cleeland, 1994] and Brief Fatigue Inventory (BFI) [Cleeland, 2010]. The BPI-SF is one 
of the most frequently used pain assessments [Cleeland, 2009] and has been used in 
various disease areas, including cancer pain and neuropathic pain [Daut, 1982; 
McDowell, 1996]. The questionnaire has demonstrated both reliability and validity across 
cultures and languages [Cleeland, 1994]. The BFI has also been used in cancer patients to 
measure fatigue [Mendoza, 1999; Chang, 2007].
Bone pain and fatigue burden will be measured by an e-Diary consisting of 7 short 
questions, including 4 questions to assess pain intensity (severity) and one question to 
assess the interference of pain with daily life activities. The items ask about pain 
experienced within the last 24 hours. It also includes 2 questions on use of pain 
medication. Fatigue will be measured by 2 short questions – one to assess the level of 
fatigue in the past 24 hours and the second to assess the interference of fatigue with 
general activity. Data from this e-Diary will be used to understand and characterize 
pain/fatigue experience and explore time to potential pain relief while controlling for the 
use of pain medication.
It is expected that the improvement in intensity of bone pain/fatigue and the impact of 
bone pain/fatigue on general activity will take place within the first 8 cycles of treatment 


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and the self-completion of the e-Diary during this period will accurately capture the 
changes in bone pain/fatigue.
Upon availability of the Bone Pain/Fatigue Assessment e-Diary, MM subjects will self-
complete the assessments at the following times:

Starting 2-4 days prior to Cycle 1 Day 1

Daily from Day 1 through Day 8 for each Cycle to time of study treatment 
discontinuation

Day 15 of each Cycle to time of study treatment discontinuation

Study Treatment Discontinuation visit
7.8.2.
Exit Interview and Follow-up Interview
To further evaluate disease and treatment related symptoms (including bone pain and 
fatigue, and visual symptoms) and associated impacts on function and health-related 
quality-of-life, participants in the Part 2 multiple myeloma cohort will complete an 
optional Exit Interview conducted via telephone.  The interview will be conducted by a 
trained interviewer and will be audio recorded for transcription and analysis.  The 
telephone interview should be conducted within 21 days following completion of the End 
of Study Treatment visit.
Subjects who have experienced ocular symptoms during the treatment period will have 
the option to also consent to participate in an optional Follow-up interview.  The Follow-
up interview will be conducted by a trained interview via telephone at least 6 months 
following the End of Study Treatment visit.  The Follow-up interview will focus on 
visual symptoms experienced by the subject, impacts on function and health-related 
quality-of-life and management and resolution of their visual symptoms following 
discontinuation of study treatment.
Both the Exit Interview and Follow-Up interview are optional, and the failure to complete 
either interview will not constitute a protocol deviation.
8.
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS
The investigator or site staff will be responsible for detecting, documenting and reporting 
events that meet the definition of an adverse event (AE) or serious adverse event (SAE) 
as outlined in Section 8.1 and Section 8.2, respectively.
8.1.
Definition of an AE
Any untoward medical occurrence in a subject or clinical investigation subject, 
temporally associated with the use of a medicinal product, whether or not considered 
related to the medicinal product.
Note: An adverse event (AE) can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease (new or exacerbated) 


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temporally associated with the use of a medicinal product.  For marketed medicinal 
products, this also includes failure to produce expected benefits, abuse, or misuse. 
Examples of events meeting the definition of an AE include:

Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or grade of the condition

New conditions detected or diagnosed after study treatment administration even 
though it may have been present prior to the start of the study

Signs, symptoms, or the clinical sequelae of a suspected 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/serious adverse event [SAE]). 
“Lack of efficacy” or “failure of expected pharmacological action” per se is not to be 
reported as an AE or SAE.  However, any signs and symptoms and/or clinical sequelae 
resulting from “lack of efficacy” will be reported as an AE or SAE, if they fulfill the 
definition of an AE or SAE. 
Events that do not meet the definition of an AE include:

Medical or surgical procedure (e.g., endoscopy, appendectomy); the condition that 
led to the procedure is an AE.

Situations where 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.

The disease/disorder being studied, or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the subject’s 
condition.
8.2.
Definition of an SAE
A serious adverse event (SAE) is any untoward medical occurrence that, at any dose:
a.
Results in death
b. Is life-threatening
NOTE:  The term 'life-threatening' in the definition of 'serious' refers to an event in 
which the subject was at risk of death at the time of the event.  It does not refer to an 
event, which hypothetically might have caused death, if it were more severe.
c.
Requires hospitalization or prolongation of existing hospitalization
NOTE:  In general, hospitalization signifies that the subject 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 out-subject setting. Complications that occur during hospitalization are 
adverse events (AEs). If a complication prolongs hospitalization or fulfills any other 


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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.
d. Results in disability/incapacity, or
NOTE:  The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions.  This definition is not intended to include experiences 
of relatively minor medical significance such as uncomplicated headache, nausea, 
vomiting, diarrhea, influenza, and accidental trauma (e.g. sprained ankle) which may 
interfere or prevent everyday life functions but do not constitute a substantial 
disruption.
e.
Is a congenital anomaly/birth defect. 
f.
Medical or scientific judgment should be exercised in deciding whether 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 subject or may require medical or surgical intervention to prevent 
one of the other outcomes listed in the above definition.  These should also be 
considered serious.  Examples of such events are invasive or malignant cancers, 
intensive treatment in an emergency room or at home for allergic bronchospasm, 
blood dyscrasias or convulsions that do not result in hospitalization, or 
development of drug dependency or drug abuse.
g. Protocol-Specific SAEs:

All events of possible study treatment-induced liver injury with 
hyperbilirubinemia defined as alanine aminotransferase (ALT) 3 times upper 
limit of normal (ULN) and bilirubin ≥2 times ULN (>35% direct) (or 
ALT ≥3 times ULN and international normalization ratio (INR) >1.5, if INR is 
measured) or termed ‘Hy’s Law’ events (INR measurement is not required and 
the threshold value stated will not apply to patients receiving anticoagulants).
NOTE:  Bilirubin fractionation should be performed.

Any new primary cancers
8.2.1.
Sentinel Events
A Sentinel Event is a GSK-defined SAE that is not necessarily drug-related but has been 
associated historically with adverse reactions for other drugs and is therefore worthy of 
heightened pharmacovigilance.  The GSK Medical Monitor is accountable for reviewing 
all SAEs for possible Sentinel Events which is mandated at GSK.  The GSK medical 
monitor may request additional clinical information on an urgent basis if a possible 
Sentinel Event is identified on SAE review.  The current GSK-defined Sentinel Events 
are listed below:

Acquired Long QT Syndrome

Agranulocytosis/Severe Neutropenia 


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
Anaphylaxis & Anaphylactoid Reactions 

Hepatotoxicity

Acute Renal Failure

Seizure

Stevens Johnson syndrome/Toxic epidermal necrosis
8.3.
Laboratory and Other Safety Assessment Abnormalities 
Reported as AEs and SAEs
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis), or 
other safety assessments (e.g., electrocardiogram [ECGs], radiological scans, vital signs 
measurements) including those that worsen from baseline, and events felt to be clinically 
significant in the medical and scientific judgment of the investigator are to be recorded as 
an adverse event (AE) or serious adverse event (SAE), in accordance with the definitions 
provided.
In addition, an associated AE or SAE is to be recorded for any laboratory test result or 
other safety assessment that led to an intervention, including permanent discontinuation 
of study treatment, dose reduction, and/or dose interruption/delay.
Any new primary cancer must be reported as a SAE. 
However, any clinically significant safety assessments that are associated with the 
underlying disease, unless judged by the investigator to be more severe than expected for 
the subject's condition, are not to be reported as AEs or SAEs.
8.3.1.
Cardiovascular Events
Investigators will be required to fill out event specific data collection tools for the 
following AEs and SAEs:  

Myocardial infarction/unstable angina

Congestive heart failure

Arrhythmias

Valvulopathy

Pulmonary hypertension

Cerebrovascular events/stroke and transient ischemic attack

Peripheral arterial thromboembolism

Deep venous thrombosis/pulmonary embolism

Revascularisation
This information should be recorded in the specific cardiovascular eCRF within one week 
of when the AE/SAE(s) are first reported.


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8.4.
Disease-Related Events and/or Disease-Related Outcomes 
Not Qualifying as SAEs
An event which is part of the natural course of the disease under study (i.e., disease 
progression or hospitalization due to disease progression) does not need to be reported as 
a serious adverse event (SAE).  Death due to disease under study is to be recorded on the 
Death electronic case report form (eCRF).  However, if the underlying disease (i.e., 
progression) is greater than that which would normally be expected for the subject, 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.
8.5.
Time Period and Frequency of Detecting AEs and SAEs
The investigator or site staff is responsible for detecting, documenting and reporting 
events that meet the definition of an adverse event (AE) or serious adverse event (SAE). 
AEs will be collected from the time the first dose of study treatment is administered until 
30 days following discontinuation of study treatment regardless of initiation of a new 
cancer therapy or transfer to hospice. 
SAEs will be collected over the same time period as stated above for AEs.  In addition, 
any SAE assessed as related to study participation (e.g., protocol-mandated procedures, 
invasive tests, or change in existing therapy), study treatment or GSK concomitant 
medication must be recorded from the time a subject consents to participate in the study 
up to and including any follow-up contact.  All SAEs will be reported to GSK within 
24 hours, as indicated in Section 8.5.2.
After discontinuation of study treatment, the investigator will monitor all AEs/SAEs that 
are ongoing until resolution or stabilization of the event or until the subject is lost to 
follow-up.  At any time after 30 days the investigator may report any AE that they 
believe possibly related to study treatment.   
8.5.1.
Method of Detecting AEs and SAEs
Care must be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended 
and non-leading verbal questioning of the subject is the preferred method to inquire about 
AE occurrence. Appropriate questions include:
“How are you feeling?” 
“Have you had any (other) medical problems since your last visit/contact?” or for 
pediatric studies, “Has your child had any (other) medical problems or seem to act 
differently in any way since his/her last visit/contact?”
“Have you taken any new medicines, other than those provided in this study, since your 
last visit/contact?” or for pediatric studies, ”Has your child needed to take any medicines, 
other than those provided in this study, since his/her last visit/contact?”


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8.5.2.
Prompt Reporting of SAEs and Other Events to GSK
Serious adverse events (SAEs), pregnancies, and liver function abnormalities and any 
other events meeting pre-defined criteria will be reported promptly by the investigator to 
GSK as described in the following table once the investigator determines the event meets 
the protocol definition for that event.
Initial Reports
Follow-up Information on a Previous 
Report
Type of Event
Time Frame
Documents
Time Frame
Documents
All SAEs
24 hours
SAE data collection 
tool
24 hours
Updated SAE data 
collection tool 
“CV events” and/or 
“death”
Initial and 
follow up 
reports to be 
completed 
within one 
week of when 
the 
cardiovascular 
event or death 
is reported
“CV events” 
and/or “death” 
data collection 
tool(s) if 
applicable
Initial and follow 
up reports to be 
completed within 
one week of when 
the cardiovascular 
event or death is 
reported
Updated “CV 
events” and/or 
“death” data 
collection tool(s) if 
applicable
Pregnancy
2 Weeks
Pregnancy 
Notification Form
2 Weeks
Pregnancy 
Follow-up Form
Liver chemistry abnormalities:
ALT 3 times ULN and 
bilirubin 2 times ULN 
(>35% direct) (or ALT 
3 times ULN and INR 
>1.5, if INR is 
measured)c
24 hoursa
SAE data collection 
tool;
Liver Event eCRF 
and liver imaging 
and/or biopsy 
eCRFs if 
applicableb
24 hours
Updated SAE data 
collection tool. 
Updated Liver Event 
eCRFb
ALT 5 times ULN; ALT 
3 times ULN with 
hepatitis or rash or 3 
times ULN 4 weeks
24 hoursa
Liver Event eCRFb
24 hours
Updated Liver Event 
eCRFb
ALT 3 times ULN and 
<5 times ULN and 
bilirubin <2 times ULN
24 hoursa
Liver Event eCRF 
does not need to be 
completed unless 
elevations persist 
for 4 weeks or 
subject cannot be 
monitored weekly 
for 4 weeksb
a.
GSK to be notified at onset of liver chemistry elevations to discuss subject safety.
b.
Liver event documents should be completed as soon as possible
c.
INR measurement is not required; if measured, the threshold value stated will not apply to subjects receiving 
anticoagulants.


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Methods for detecting, recording, evaluating, and following up on adverse events (AEs) 
and serious adverse events (SAEs) are provided in the Study Procedures Manual (SPM).
8.5.3.
Regulatory reporting requirements for SAEs
Prompt notification of serious adverse events (SAEs) by the investigator to GSK is 
essential so that legal obligations and ethical responsibilities towards the safety of 
subjects are met.
GSK has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a product under clinical investigation.  GSK will 
comply with country specific regulatory requirements relating to safety reporting to the 
regulatory authority, institutional review board (IRB)/ethics committee (EC) and 
investigators.
Investigator safety reports are prepared for suspected unexpected serious adverse 
reactions according to local regulatory requirements and GSK policy and are forwarded 
to investigators as necessary.
An investigator who receives an investigator safety report describing a SAE(s) or other 
specific safety information (e.g., summary or listing of SAEs) from GSK will file it with 
the IB and will notify the IRB/EC, if appropriate according to local requirements.
9.
LIVER CHEMISTRY FOLLOW-UP PROCEDURES
9.1.
Liver Chemistry Testing Procedures
For subjects meeting any of the liver chemistry stopping criteria in Section 3.9.1, make 
every attempt to carry out the liver event follow-up assessments described below:

Viral hepatitis serology, including:

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, then obtain 
heterophile antibody or monospot testing)

Blood sample for pharmacokinetic (PK) analysis. Record the date and time of 
the PK blood sample draw and the date and time of the last dose of study drug 
prior the blood sample draw on the eCRF.  If the date or time of the last dose is 
unclear, provide the subject’s best approximation.  If the date or time of the last 
dose cannot be approximated, or if a PK sample cannot be collected within 48 
hours of the liver chemistry event, do not obtain a PK sample.  Instructions for 
sample handling and shipping are found in the Study Procedures Manual (SPM).

Serum creatinine phosphokinase (CPK) and lactate dehydrogenase (LDH)


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
Fractionate bilirubin, if total bilirubin 2 X upper limit of normal (ULN)

Obtain a complete blood count (CBC) with differential to assess eosinophilia

Record the appearance or worsening of clinical symptoms indicative of hepatitis 
or hypersensitivity, such as fatigue, nausea, vomiting, right upper quadrant pain 
or tenderness, fever, rash or eosinophilia as relevant on the AE eCRF

Record the use of concomitant medications, including acetaminophen, herbal 
remedies or any other over the counter (OTC) medications, or any putative 
hepatotoxins, on the concomitant medication eCRF

Record alcohol use on the liver event alcohol intake eCRF
The following assessments are required for subjects with ALT 3 X ULN and bilirubin 
2X ULN (>35% direct) but are optional for other abnormal liver chemistries:

Anti-nuclear antibody, anti-smooth muscle antibody, and Type 1 anti-liver 
kidney microsomal antibodies

Liver imaging (ultrasound, magnetic resonance imaging [MRI] or computed 
tomography [CT]) to evaluate liver disease
9.2.
Liver Chemistry Monitoring Criteria
For subjects with ALT 3 X ULN but <5X ULN and bilirubin <2 X ULN, without 
symptoms indicative of hepatitis or rash, and who can be monitored safety for 4 weeks, 
the following actions should be taken:

Notify the GSK Medical Monitor within 24 hours of learning of the abnormality 
to discuss subject safety

Continue administration of study drug

Evaluate liver chemistries (ALT, AST, alkaline phosphatase, bilirubin) weekly 
until they resolve, stabilize or return to within baseline levels

If at any time the subject meets any of the liver chemistry stopping criteria 1 to 5 
(Section 3.9.1), then proceed as described in Section 9)

If, after 4 weeks of monitoring, ALT <3X ULN and bilirubin <2 X ULN, then 
monitor subjects twice monthly until liver chemistries normalize or return to 
within baseline values
9.3.
Drug Restart/Rechallenge Following Liver Events that are 
Possibly Related to Study Drug
Approval by the GSK Medical Monitor to restart/rechallenge study drug may be 
considered where:

The subject is receiving compelling benefit, the benefit exceeds the risk, and no 
effective alternative therapy is available.  Approval of restart/rechallenge by the 
Institutional Review Board (IRB) or Independent Ethics Committee (IEC) must 
be obtained, as required  


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
If the restart/rechallenge is approved by GSK in writing, then the subject must 
be provided with a clear description of the possible benefits and risks of 
administration of study drug, including the possibility of a recurrence, a more 
severe liver injury or death.

The subject must also provide signed informed consent specifically for the study 
drug restart/rechallenge.  Documentation of the informed consent must be 
recorded in the subject’s study chart.

Study drug must be administered at the dose specified by the GSK Medical 
Monitor.

Subjects approved by GSK for restart/rechallenge of study drug must return to 
the clinic twice a week for evaluation of liver chemistry tests until stable liver 
chemistries have been demonstrated and laboratory monitoring may resume per 
protocol.
9.4.
Drug Restart Following Transient, Resolving Liver Events 
Not Related to Study Drug
Approval by the GSK Medical Monitor to restart study drug(s) may be considered where:

Liver chemistry abnormalities 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 <3X ULN.  Approval of restart by the 
Institutional Review Board (IRB) or Independent Ethics Committee (IEC) may 
be required.  

If the restart/rechallenge is approved by GSK in writing, then the subject must 
be provided with a clear description of the possible benefits and risks of 
administration of study drug(s), including the possibility of a recurrence, a more 
severe liver injury or death.

The subject must also provide signed informed consent specifically for the study 
drug(s) restart/rechallenge.  Documentation of the informed consent must be 
recorded in the subject’s study chart.

Study drug(s) must be administered at the dose specified by the GSK Medical 
Monitor.

Subjects approved by GSK for restart/rechallenge of study drug(s) must return 
to the clinic once a week for evaluation of liver chemistry tests until stable liver 
chemistries have been demonstrated and laboratory monitoring may resume per
protocol.

If protocol-defined stopping criteria for liver chemistry abnormalities are met, 
study drug(s) administration must stop.


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10.
CONCOMITANT MEDICATIONS AND NON-DRUG 
THERAPIES
Subjects will be instructed to inform the investigator prior to starting any new 
medications from the time of first dose of study treatment until the end of the study (Final 
Study Visit).  Any concomitant medication(s), including non-prescription medication(s) 
and herbal product(s), taken during the study will be recorded in the electronic case 
report form (eCRF).  Additionally, a complete list of all prior anti-cancer therapies will 
be recorded in the eCRF.
Concomitant dosing of GSK2857916 with strong Pgp inhibitors should be avoided unless 
considered medically necessary (See Appendix 11:  Pgp Inhibitors for list of relevant Pgp 
inhibitors).
If future changes are made to the list of permitted/prohibited medications, formal 
documentation will be provided by GSK and stored in the study file.  The SPM will be 
updated to include this information. Any such changes will be communicated to the 
investigative sites in the form of a letter.
10.1.
Permitted Medication(s)
Subjects should receive full supportive care during the study, including transfusion of 
blood and blood products, growth factors, and treatment with antibiotics, anti-emetics, 
antidiarrheals, and analgesics, as appropriate.
Steroids are not allowed unless used for pre-medication prior to GSK2857916 infusion.
Concomitant therapy with biphosphonates is allowed.
Concomitant prophylactic treatment for tumor lysis syndrome (according to local 
standards) in subjects with high tumor load, where TLS may occur is permitted and 
should be considered.
10.2.
Prohibited Medication(s)
Chronic treatment with oral steroids is prohibited while the subject is on study. 
A short course (up to 7 days) of steroids can be used to manage rash, treatment induced 
diarrhea, or other acute complications. Steroids may be used to treat infusion related 
reactions. Inhaled steroids are allowed.
10.3.
Permitted Non-Drug Therapies
Subjects may receive local irradiation for pain control or stability control. 
10.4.
Prohibited Non-Drug Therapies
Plasmapheresis is prohibited from 7 days prior to study entry through the end of study.  


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11.
LIFESTYLE AND/OR DIETARY RESTRICTIONS
11.1.
Contraception
11.1.1.
Female Subjects
A female of non-childbearing potential (i.e., physiologically incapable of becoming 
pregnant) is defined as any female who has had a hysterectomy, bilateral oophorectomy 
(ovariectomy) or bilateral tubal ligation, or is post-menopausal 
A practical definition accepts menopause after 1 year without menses with an appropriate 
clinical profile, e.g., age appropriate, >45 years in the absence of hormone replacement 
therapy (HRT).  In questionable cases, the subject must have a follicular stimulating 
hormone (FSH) value >40 mIU/mL and an estradiol value < 40pg/mL (<140 pmol/L).
A female of childbearing potential is defined as any female who does not meet the 
criteria of non-childbearing potential as described in the previous paragraph.
Female subjects of childbearing potential must not become pregnant during the study and 
so must be sexually inactive by abstinence or use contraceptive methods with a failure 
rate of <1%.
Abstinence
Sexual inactivity by abstinence must be consistent with the preferred and usual lifestyle 
of the subject.  Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-
ovulation methods) and withdrawal are not acceptable methods of contraception. 
Complete abstinence from sexual intercourse for 14 days prior to first dose of study 
treatment, through the dosing period, and for at least 60 days after the last dose of study 
treatment.
Contraceptive Methods with a Failure Rate of <1%

Oral contraceptives (either combined or progesterone only) if not contraindicated for 
this subject population or per local practice. 

Estrogenic vaginal ring if not contraindicated for this subject population or per local 
practice. 

Percutaneous contraceptive patches if not contraindicated for this subject population 
or per local practice. 

Implants of levonorgestrel if not contraindicated for this subject population or per 
local practice.  

Injectable progesterone if not contraindicated for this subject population or per local 
practice. 

Intrauterine device or intrauterine system that meets the <1% failure rate as stated in 
the product label


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
Male partner sterilization (vasectomy with documentation of azoospermia) prior to 
the female subject's entry into the study, and this male is the sole partner for that 
subject.  For this definition, “documented” refers to the outcome of the 
investigator's/designee’s medical examination of the subject or review of the 
subject's medical history for study eligibility, as obtained via a verbal interview with 
the subject or from the subject’s medical records.

Double-barrier method: condom and occlusive cap (diaphragm or cervical/vault 
caps) plus vaginal spermicidal agent (foam/gel/film/cream/suppository) 
These allowed methods of contraception are only effective when used consistently, 
correctly and in accordance with the product label.  The investigator is responsible 
for ensuring subjects understand how to properly use these methods of 
contraception.
11.1.2.
Male Subjects
To prevent pregnancy in a female partner or to prevent exposure of any partner to the 
study treatment from a male subject’s semen, male subjects must use one of the following 
contraceptive methods:

Abstinence, defined as sexual inactivity consistent with the preferred and usual 
lifestyle of the subject.  Periodic abstinence (e.g. calendar, ovulation, symptothermal, 
post-ovulation methods) and withdrawal are not acceptable methods of 
contraception.
Complete abstinence from sexual intercourse from the first dose of study medication, 
throughout the study treatment period and for at least 60 days after the last dose of 
study treatment.

Condom (during non-vaginal intercourse with any partner - male or female) OR

Double-barrier method: condom and occlusive cap (diaphragm or cervical/vault 
caps) plus spermicidal agent (foam/gel/film/cream/suppository) (during sexual 
intercourse with a female)
11.2.
Lactation Restrictions
Female subjects who are lactating must discontinue nursing prior to the first dose of study 
treatment and must refrain from nursing throughout the treatment period and for 4 
months following the last dose of study treatment.
12.
DATA MANAGEMENT
For this study, data will be collected using defined electronic case report forms (eCRFs), 
transmitted electronically to GSK and combined with data provided from other sources in 
a validated data system.
Management of clinical data will be performed in accordance with applicable GSK 
standards and data cleaning procedures to ensure the integrity of the data, e.g. removing 
errors and inconsistencies in the data.  AEs and concomitant medications terms will be 
coded using Medical Dictionary for Regulatory Activities (MedDRA) and an internal 


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validated medication dictionary, GSK Drug.  Electronic CRFs (eCRFs), including queries 
and audit trails, will be retained by GSK, 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 GSK at agreed times.
In all cases, subject initials will not be collected or transmitted to GSK according to GSK 
policy.
12.1.
Data Dissemination and Communication Plan
The GSK Medical Monitor will review screening packets to ensure that subjects being 
considered for enrolment meet eligibility criteria prior to entering the study.  Subjects 
will not be assigned a study number until their screening packet is reviewed and approved 
by the GSK Medical Monitor.  GSK will remain in constant contact with the clinical sites 
during the enrolment period to ensure that cohort enrolment in Parts 1 and 2 of this study 
are completed as per protocol.  Investigators will be informed about available openings 
for enrolment on the trial and will be asked to pre-screen their subjects to determine 
potential eligibility, and to avoid over-enrolment. Enrollment will be offered to a given 
site for a limited period of time, and if the site chosen cannot successfully enrol a subject 
within a pre-specified time period then another site will be offered the opportunity to 
enrol a subject.  
During Part 1 of the study, Study Team Safety Update Meetings will be held every three 
weeks to review relevant data with the Principal Investigators (or delegates) and site staff. 
These meetings will be held on an “as needed” basis (but no less frequent than once a 
month) during Part 2 (e.g., to share safety experience and to communicate results of 
scheduled futility analyses).  Safety, PK, PD, and clinical outcome data available for all 
subjects at the time of the scheduled Safety Update Meeting will be reviewed and 
summarized.  In addition, Dose Escalation Meetings will be scheduled at the conclusion 
of the DLT assessment period for subjects enrolled in each cohort to review safety PK, 
and PD data and determine the next dose level appropriate for study. Dose escalation 
decisions will be made with team and investigator agreement after review of available 
safety data from at least one cycle of therapy with GSK2867916 (i.e., 21 days for the 
once every 3 weeks schedule and 28 days for weekly schedule).  All dose escalation or 
safety decisions will be documented in writing with copies maintained at each site and 
the Master Study Files at GSK.  Available data will be provided to participants prior to 
each scheduled Safety or Dose Escalation Meeting.
Attendees of Safety Update and Dose Escalation Meetings will include but not limited to 
all clinical investigators (or designees) and site staff, the GSK Medical Monitor, Clinical 
Investigation Lead, Clinical Operations Study Lead (USA and Local Operating Company 
designees), Data Quality Leader, Global Clinical Safety and Pharmacovigilance 
Representative, Statistician, CPMS representative, and Translational Medicine Lead.


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13.
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS
13.1.
Hypothesis(es)
13.1.1.
Part 1: Dose-Escalation Phase
No formal statistical hypotheses are being tested in Part 1.  Analysis of the data obtained 
from Part 1 will only utilize descriptive methods.
13.1.2.
Part 2: Expansion Cohort
For Part 2, hypothesized response rates are provided in Section 13.2.2 below.  In this 
case, a test that the ORR is less than or equal to the null hypothesis rate versus the ORR 
is greater than or equal to the alternative rate will be performed using the stopping rules 
provided in Section 13.6.2.  Descriptive statistics will be used to describe the observed 
ORRs at the RP2 dose used in the expanded cohorts.
13.2.
Sample Size Determination
The sample size planned for Part 1 arises from the predefined criteria for dose selection 
and is not driven by statistical considerations.  Based on simulations, the anticipated size 
of Part 1 will be approximately 20 subjects. See Section 13.2.1 and Section 13.2.2 for 
more details.
The additional 50 subjects in the expanded cohort for Part 2 of the study (which includes 
approximately 40 MM subjects and approximately 10 subjects with other BCMA positive 
malignancies) will provide additional safety and tolerability information about the 
treatment and a better precision around the response rate estimate.
13.2.1.
Part 1: Dose-Escalation Phase
The total number of subjects to be enrolled in Part 1 will depend on the number of 
subjects needed to characterize the individual dose cohorts for determination of the MTD.    
Simulations were conducted to determine the average sample size and percentage of 
times each dose was selected under three different scenarios.  These scenarios were 
designed to represent true toxicity profiles which are lower than expected, higher than 
expected, and in line with expectations. For each scenario, 1000 clinical trials were 
simulated.  Details are provided in Table 16.  Doses are the projected doses.  Actual 
doses used during the conduct of the trial may vary.
The specified prior probabilities discussed in Section 3.3.1.2.3  were used to determine an 
explicit equation for the prior distribution using the FACTS software.  The parameters 
(s.d.) of the explicit distribution are =-1.3281 (1.7153), ln()=-0.795 (1), and ρ=-0.9352 
where and ln() are distributed as bivariate normal with correlation ρ.


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Table 16
Simulation Results Under Various Scenarios
Dose
(mg/kg)
Scenario 1: Below Level of 
Toxicity
Scenario 2: Expected Level 
of Toxicity
Scenario 3: Higher Level of 
Toxicity
True DLT 
Rate
Percent of 
Trials 
Selecting 
Dose as 
MTD (%)
True DLT 
Rate
Percent of 
Trials 
Selecting 
Dose as 
MTD (%)
True DLT 
Rate
Percent of 
Trials 
Selecting 
Dose as 
MTD (%)
No Dose
0
0.7
6.8
0.03
0
0
0.001
0
0.05
0.2
0.06
0.01
0
0.02
0
0.075
0.1
0.12
0.025
0
0.05
0.4
0.1
2.6
0.24
0.05
0.1
0.1
1.4
0.15
5.3
0.48
0.075
0.7
0.15
6.7
0.2
20.3
0.96
0.1
4.3
0.2
20.3
0.3
29.0
1.92
0.125
14.1
0.225
30.3
0.35
24.6
2.8
0.15
22.6
0.275
27.9
0.375
9.5
3.6
0.175
22.4
0.35
9.1
0.45
1.2
4.5
0.225
35.8
0.425
3.2
0.55
0.4
The average sample size over the 1000 clinical trials simulated under each of Scenarios 
1-3 was 20.55, 20.04, and 19.43 respectively.
13.2.2.
Part 2: Expansion Cohort
Dose escalation will be used to establish the RP2 dose for GSK2857916.  Once the RP2 
dose is confirmed, at least 15 and up to 40 subjects in total will be enrolled into the MM 
cohort using decision rules defined in Table 17.  The sample size and stopping rules are 
based on the methodology of Lee et al. [Lee, 2008].  The assumptions underlying the 
design are detailed below. 
The null hypothesis is:
H0: p≤20%
The alternative hypothesis is:
HA:p≥40%


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For the MM expansion cohort, starting with 15 subjects and allowing for a maximum 
sample size of 40, this design will have a type I error rate () of 0.075 and 89.8% power.  
The trial is not designed to stop early for efficacy, but is designed to stop early for futility 
if the predictive probability of success is less than 5%.  The type I error rate, power, and 
predictive probability of success to stop early for futility were derived from explicitly 
stating the minimum and maximum sample size, allowing for the futility stopping rate to 
range from 5% to 20% within the predictive probability design software, and selection of 
the optimizing criterion as the maximization of power under the alternative hypothesis.  
The Bayesian prior probability used in determining the design was Beta (0.25, 0.75), a 
distribution with a mean response rate of 25%.  Under the null hypothesis, if the true 
response rate is 20%, the expected sample size of the design is 23.4 subjects and 
probability of early termination (PET) is 88.9%.  Under the alternative hypothesis, if the 
true response rate is 40%, the expected sample size of the design is 38.6 subjects and 
probability of early termination (PET) is 8.5%.  
13.3.
Sample Size Sensitivity
13.3.1.
Sample Size Re-estimation
Sample size re-estimation is not planned for this study.
13.4.
Data Analysis Considerations
Data will be listed and summarized according to GSK integrated data standards library 
(IDSL) reporting standards and the Clinical Data Interchange Standards Consortium 
(CDISC) where applicable. Complete details will be provided in the Reporting and 
Analysis Plan (RAP).
13.4.1.
Analysis Populations
The ‘All Treated’ population is defined as all eligible subjects who receive at least 1dose 
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. 
Subjects 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 or 28 days for once weekly schedule) for reasons other than toxicity may be 
presented in separate tables/listings.
The ‘All Treated’ population will further be classified in the following sub-populations.
o
Part 1: all Part 1 subjects of All Treated population. Note, subjects in Part 1 are 
exclusively multiple myeloma patients. 
o
Part 2 MM: all Part 2 MM subjects of All Treated population 
o
All Treated MM: comprise of subjects in Part 1 and Part 2 MM.
o
Part 2 NHL: all Part 2 lymphoma subjects of All Treated population.


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The ‘DLT Evaluable’ population in Part 1 enables an appropriate evaluation of study 
DLTs. It is defined as those subjects fulfilling the ‘All Treated’ population criteria, and 
having met the following adequate exposure criteria: 
o
For Schedule 1 (once every 3 weeks dosing) subjects received a complete infusion 
in cycle 1. 
o
For Schedule 2 (once weekly dosing for 3 consecutive weeks, 1 week rest) 
subjects receive three infusions, two of which must be complete infusions, in 
cycle 1. (as increases up to ≤30% are implemented between cohorts, less than 2 
complete infusions would result in a total dose closer to the previous dose 
investigated).
Any subject in the “All Treated” population who experiences a DLT, as defined in 
Section 3.3.3 will also be included in the DLT evaluable population regardless of 
exposure.
The ‘Evaluable (MM)’ population is a subset of the ‘All Treated’ population, who were 
initially treated at RP2D in the expansion cohort and have at least two post-baseline disease 
assessments or they have progressed or died or permanently discontinued treatment. This 
population will be used for the futility analysis of the MM expansion cohort.
The ‘Pharmacokinetic (PK) Population’ is defined as those subjects in the “All 
Treated” population from whom at least one PK sample was obtained, analyzed, and was 
measurable. 
The ‘Pharmacodynamic (PD) Population’ is defined as those subjects in the “All 
Treated” population from whom at least one PD sample was obtained, analyzed, and was 
measurable.
13.5.
Treatment Comparisons
13.5.1.
Primary Comparisons of Interest
No formal hypothesis testing will be performed. Safety, PK, PD markers, and efficacy 
summaries will be provided by initial dose cohort in Part 1 and by expansion cohort in 
Part 2.
13.5.1.1.
Primary Comparison of Interest
All available data, including adverse events, changes in laboratory values and other safety 
parameters will be evaluated for each dose cohort in Part 1 and for each expansion cohort 
in Part 2.
13.5.2.
Other Comparisons of Interest
Pharmacokinetic: PK parameters will be evaluated and summarized for each dose cohort 
in Part 1 and in Part 2. 


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Pharmacodynamic markers: Changes from baseline in PD markers will be evaluated and 
summarized for each dose cohort in Part 1 and for Part 2.
Clinical anti-cancer activity: The number of Overall Responders (PR, VGPR, CR or sCR) 
for each dose cohort in Part 1 and for each expansion cohort in Part 2 will be listed and 
summarized if data warrant. Clinical Benefit Rate (CBR), as defined in Appendix 1, may 
also be explored.  The results from the independently reviewed scans may also be 
reported if data are available.


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13.6.
Interim Analysis
13.6.1.
Part 1
While no formal interim analysis is planned for Part 1, safety, pharmacokinetic and 
pharmacodynamic marker data will be examined on an ongoing basis to support dose 
escalation decisions. Prior to determining the GSK2857916 dose for the next cohort 
enrolled, exploratory analysis will be conducted to assess the relationship of 
GSK2857916 dose levels with safety, PK and PD parameters using all data from 
available cohorts. For more details of the dose escalation procedure, see Section 3.3. 
13.6.2.
Part 2
The methodology utilized is based on the predictive probability of success if enrollment 
continues to 40 subjects [Lee, 2008]. The predictive probability design is similar to a 
Green-Dahlberg design in that it allows for early stopping for futility.  The differences 
are that the predictive probability design allows for evaluation of stopping rules as often 
as after each subject, rather than at only two stages.  While the two designs have similar 
type I and type II error rates, the probability of early termination is greater with the 
predictive probability design. In this particular study, we will stop only for futility and 
evaluate the stopping rules once approximately 15, 22, and 30 subjects are evaluable 
(though additional futility looks are also controlled for if necessary). A subject is 
considered evaluable if they are in the all treated population and have had at least two 
post baseline disease assessments.
For the MM expansion cohort, response data will be reviewed once approximately 15, 22, 
and 30 subjects are evaluable and the number of overall responses (PR, VGPR, CR, and 
sCR) observed will be compared with the stopping rules provided in Table 17 below. 


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Table 17
Futility Stopping Region
Number of Overall Responses
Number of Evaluable Subjects
0
1
2
3
4
5
6
7
8
9
10
11
>11
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
Note: The shaded regions are the specific regions for stopping the study for futility.  For 
instance, if there are 4-5 or fewer responses in 25 subjects, then the predictive probability 
for success will be less than the futility criterion, 5.0%, and the study will be stopped.
In addition to the considering the recommendations of the futility analyses, final 
decisions on stopping enrolment in the MM cohort will depend on the totality of the data 
collected. Examples of consideration of the totality of the data include, further 
investigation of the clinical activity of subgroups of subjects based on their BCMA 
expression levels and evaluation of the quality of responses (including sCR, CR and 
Clinical Benefit Rate, as defined in Appendix 1). Should the recommendation to stop for 
futility be disregarded in favor of a decision to continue the trial based on the totality of 
the data, the overall type I error rate of the expansion phase will be inflated.  


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No interim analyses will be performed on the BCMA+ lymphomas cohort; though 
consideration would be given to closing the cohort should the enrollment be stopped in 
the MM cohort. 
If necessary, a subject may be replaced if they are deemed to be Lost to Follow-Up 
(LTFU) or they have withdrawn due to a toxicity deemed to not have been related to 
GSK2857916.
Subjects will not be replaced when they discontinue the study due to: Progression 
(symptomatic or otherwise), toxicity related to GSK2857916, or lack of efficacy.
Other administrative interim analyses may be performed if needed.
Final analysis of MM population may be performed separately, before the NHL cohort 
completes the study. 
13.7.
Key Elements of Analysis Plan
Data will be listed and summarized according to the GSK reporting standards, where 
applicable.  Complete details will be documented in the Reporting and Analysis Plan 
(RAP).  Any deviations from, or additions to, the original analysis plan described in this 
protocol will be documented in the RAP and final study report.
As it is anticipated that accrual will be spread thinly across centers and summaries of data 
by center would be unlikely to be information, data from all participating centers will be 
pooled prior to analysis.
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 subject will depend on efficacy and tolerability, 
the duration of follow-up will vary between subjects.  Consequently there will be no 
imputation for missing data. 
Demographic and baseline characteristics will be summarized.
13.7.1.
Anti-Cancer Activity Analyses
The All Treated Population will be used for anti-cancer activity analyses. Since this is a 
Phase I study, anti-cancer activity will be evaluated based on clinical evidence and 
response criteria.  If data warrant, the response data will be summarized by dose level.  
Correlation analysis will be conducted to explore any relationship between the tumor 
response based on either the International Myeloma Working Group Uniform Response 
Criteria (for subjects with MM; see Appendix 1) or the Response Criteria for Malignant 
Lymphoma (for subjects with lymphomas, refer to Appendix 2). Full details will be 
specified in the Reporting and Analysis Plan (RAP). 


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13.7.2.
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, electrocardiogram [ECGs]) 
will be summarized 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 Reporting and Analysis Plan (RAP).
13.7.2.1.
Extent of Exposure
The number of subjects administered study treatment will be summarized according to 
the duration of therapy.  
13.7.2.2.
Adverse Events
Adverse events (AEs) will be coded using the standard MedDRA and grouped by system 
organ class.  Adverse events (AEs) will be graded by the investigator according to the 
National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), 
(version 4).
Events will be summarized by frequency and proportion of total subjects, by system 
organ class and preferred term.  Separate summaries will be given for all AEs, treatment-
related AEs, serious adverse events (SAEs) and AEs leading to discontinuation of study 
treatment. Adverse events (AEs), if listed in the NCI-CTCAE (version 4) will be 
summarized by the maximum grade.  Otherwise, the AEs will be summarized by 
maximum intensity.
Characteristics (e.g. number of occurrences, action taken, grade, etc) of the following 
AEs of clinical interest will be summarized separately: corneal events, hematologic 
toxicities (including but not limited to thrombocytopenia and neutropenia), infusion 
related reaction etc. Details will be provided in the RAP.
The incidence of deaths and the primary cause of death will be summarized.
13.7.2.3.
Clinical Laboratory Evaluations
Hematology and clinical chemistry data will be summarized using frequencies and 
proportions according to National Cancer Institute-Common Toxicity Criteria for 
Adverse Events (NCI-CTCAE) (Version 4.0).  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.


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The worst-case- toxicity grade in hematology and chemistry result during the treatment 
will be summarized. Shift tables from baseline to the worst toxicity grade during 
treatment will be provided for each laboratory analyte.
Further details will be provided in the Reporting and Analysis Plan (RAP).
13.7.2.4.
Immunogenicity Analyses
For each subject, the results and titers of anti-GSK2857916 binding antibodies will be 
listed for each assessment time point.  The frequency and percentage of subjects with 
positive and negative results will be summarized for each assessment time and overall for 
each subject by dose cohort.
13.7.2.5.
Other Safety Measures
Data for vital signs, electrocardiograms (ECGs), and echocardiograms (ECHOs) will be 
summarized 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 
Reporting and Analysis Plan (RAP).


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13.7.3.
Pharmacokinetic Analyses
13.7.3.1.
Raw Plasma Concentrations
Linear and semi-logarithmic individual plasma concentration-time profiles and mean and 
median profiles (when applicable) by GSK2857916 dose and schedule will be plotted for 
both GSK2857916 (intact and total) and cys-mcMMAF in Part 1.
In Part 2, individual model-predicted GSK2857916 plasma concentration-time profiles, 
observed concentrations in individual subjects and population predicted plasma 
concentrations provided by NONMEM (non-linear mixed effects modelling), will be 
presented graphically by subject (semi-log plot) and by treatment (linear and semi-log 
plots).
Plasma concentrations of GSK2857916 (intact and total) and cys-mcMMAF will be listed 
for each subject and summarized by planned time point, dose cohort and schedule in Part 
1and Part 2.
Derived Plasma Pharmacokinetic Parameters
Pharmacokinetic analysis will be the responsibility of the CPMS Department, QSci, 
GSK.
In Part 1 of the study, plasma GSK2857916 concentration-time data will be analyzed by 
non-compartmental methods using WinNonlin. Calculations will be based on the actual 
sampling times recorded during the study. From the plasma concentration-time data, the 
following GSK2857916 (intact and total) PK parameters will be determined as data 
permit, for each dose of GSK2857916, each schedule and for each subject: 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). After repeat dose: Cmax and Ctrough.
For cys-mcMMAF, after single dose, Cmax and AUC(0-t) will be derived and after 
repeat dose Cmax and Ctrough.
In Part 2 of the study, plasma GSK2857916 concentration-time data together with data 
from part 1 will be analysed using a population approach. A nonlinear mixed effects 
model will be used to determine population pharmacokinetic parameters and identify 
relevant covariates (e.g., age, weight, or disease related covariates). PK parameters will 
be listed and summarized descriptively (mean, standard deviation, median, minimum, 
maximum, geometric mean, and the standard deviation, CV% and 95% confidence 
interval of log-transformed parameters) by dose cohort and schedule in Part 1 and Part 2.  
To assess the extent of accumulation following GSK2857916 repeat dosing, the observed 
accumulation ratio (Ro) for both GSK2857916 (intact and total) and cys-mcMMAF will 
be determined as Cmax and Ctrough at steady-state to Cmax and Ctrough after the first 
dose, respectively.


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Raw urine Concentrations
Urine concentrations of cys-mcMMAF (part 1 only) will be listed and summarised by 
GSK2857916 dose, schedule and nominal time range. Plots may also be produced if 
deemed necessary.
Derived Urine Pharmacokinetic Parameters
If data permits, the following pharmacokinetic parameters will be determined for each 
GSK2857916 dose, each schedule and for each subject (Part 1 only):
Urinary recovery of unchanged cys-mcMMAF within the 24 h period collection (Ae(0-
24)) will be calculated. It will be calculated as the product of the concentration in urine 
and the urine weight, thus assuming a urine density of 1 g/mL.
Fraction of total cys-mcMMAF dose excreted (Fe) in the 24-h interval will be estimated 
as Ae(0-24)/(cys-mcMMAF)Dose, in the Schedule 1only (i.e. every 3weeks).
Derived cys-mcMMAF urine pharmacokinetic parameters will be listed and summarised 
by GSK2857916 dose and schedule.
13.7.3.2.
Statistical Analysis of Pharmacokinetic Data
Statistical analyses of the pharmacokinetic (PK) parameters data will be the responsibility 
of Discovery Biometrics, GSK.
GSK2857916 (intact and total) and cys-mcMMAF concentration-time data will be listed 
for each subject and summarized by descriptive statistics at each time point by cohort.  
Dose Proportionality: In Part 1, if more than 2 dose cohorts are required to reach RP2 
dose, exploration of dose proportionality for GSK2857916 (intact and total) and 
Cys-mcMMAFAUC(0-∞)/AUC(0-tau) and Cmax following single dose administration 
and GSK2857916 (intact and total) and cys-mcMMAF Cmax and Ctrough following 
repeat dose administration will be evaluated graphically and using the power model as 
described below:
where a is the y-intercept and b is the slope.
The power model will be fitted by restricted maximum likelihood (REML) using SAS 
Proc Mixed. Both the intercept and slope will be fitted as fixed effects. If there is 
sufficient data, the model may also be fit with the intercept and/or slope as random 
effects depending on the ability of the model to converge and on estimation of variance-
covariance matrix. The mean slope and corresponding 90% confidence interval will be 
estimated from the power model.


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13.7.4.
Pharmacokinetic/Pharmacodynamic Analyses
Exploratory plots will be presented to examine potential relationships between individual 
and/or pooled plasma concentrations/exposure and relevant safety and PD endpoints. If 
deemed appropriate, further PK/PD modelling will be performed on the safety and PD 
endpoints selected based on the results of the exploratory graphical analysis showing 
obvious relationships or trends between the dose, concentration/exposure and the safety 
and PD endpoints. The choice of the structural PK/PD models will be dependent on the 
emerging data. More details of any exploratory PK/PD analyses will be provided in the 
RAP.
The exposure response relationship between GSK2857916 (dose, concentration, Cmax, 
or AUC) and clinical activity (e.g. ORR) will also be explored combining Part 1 and Part 
2 data together if deemed appropriate.
13.7.4.1.
Translational Research Analyses
The results of translational research investigations will be reported either within or 
separately from the main clinical study report (CSR).  All endpoints of interest from all 
comparisons will be descriptively and/or graphically summarized as appropriate to the 
data.
Further details on the translational research analyses will be addressed in the Reporting 
and Analysis Plan (RAP).
13.7.4.2.
Novel Biomarker(s) Analyses
The results of these biomarker investigations may be reported separately from the main 
clinical study report.  All endpoints of interest from all comparisons will be descriptively 
and/or graphically summarized as appropriate to the data.
Additional exploratory analyses may be performed to further characterize the novel 
biomarker.
13.7.5.
Genetic Analyses
Further details on genetic analyses will be addressed in Appendix 7.
13.7.6.
Pharmacodynamic Biomarkers and Exploratory Response 
Prediction Biomarkers
Cell surface BCMA and sBCMA pre dosing will be quantified as a potential predictive 
biomarker for clinical activity.  Post dosing, free surface BCMA and BCMA-drug 
complex will be quantified to assess proportion of target engagement. 
Measurements of sBCMA will include separate assays for free sBCMA and sBCMA 
complexed with drug. 
Post dose measurements of free and complexed BCMA will be used in conjunction with 
PK data to understand drug/ target interaction during dosing. 


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If the data permit, an attempt will be made to identify a statistically and clinically 
meaningful threshold for BCMA expression which serves as an indicator for potential 
efficacy. Full details of analysis approaches will be provided in the RAP. 
13.7.6.1.
Exploratory analyses of DNA, and Protein
Exploratory analyses may be performed on remaining study samples for analyses of 
DNA, RNA and protein to understand changes in response to GSK2857916 treatment.
The results of exploratory investigations will be reported separate from the main clinical
study report (CSR).  All endpoints of interest from all comparisons will be descriptively 
and/or graphically summarized as appropriate to the data. 
13.7.7.
Clinical Activity Analyses
Overall Response Rate ORR) is one of the secondary endpoints to measure clinical 
activity of this study.  
For multiple myeloma, ORR is defined as the percentage of subjects with a confirmed PR 
or better (i.e. PR, VGPR, CR and sCR), according to the IMWG Panel I (Appendix 1), as 
assessed by the investigator. In addition, Clinical Benefit rate (CBR) is defined as the 
percentage of subjects with a confirmed MR or better (i.e.MR, PR, VGPR, CR and sCR), 
according to the IMWG Panel I (Appendix 1), as assessed by the investigator.
The number and percentage of subjects in the following response categories will be 
presented sCR (stringent complete response), (complete response) CR, (very good partial 
response) VGPR, (partial response) PR, (minimal response) MR, stable disease (SD), 
progressive disease (PD), and not evaluable (NE)
sCR+CR+VGPR+PR for overall response (ORR)
sCR+CR+VGPR+PR+MR for Clinical Benefit rate (CBR)
The corresponding exact 95% CI for ORR and Clinical Benefit Rate (CBR) will also be 
provided.  Subjects with unknown or missing response will be treated as non-responders, 
i.e., these subjects will be included in the denominator when calculating percentages of 
response.
For lymphoma, ORR is defined as the percentage of subjects with confirmed CR, or PR, 
as described in the Revised Response Criteria for Malignant Lymphoma (Appendix 2). 
ORR for lymphomas will be summarized in a similar way as multiple myeloma. The 
corresponding exact 95% CI for ORR will also be provided.
Other exploratory time-to-event (TTE) endpoints related to clinical activity for Part 2 
(MM) of this study are TTP, DOR, TTR, and PFS.
Time to disease progression (TTP) is defined as the time from first dose until the 
earliest date of PD per IMWG, or death due to PD. Determination of dates of TTP event 
and dates for censoring will be described in the RAP. Duration of response (DOR) is 
defined as the time from first documented evidence of PR or better until disease 
progression (PD) per IMWG, or death due to PD among subjects who achieve a response 


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(i.e. confirmed PR or better). Responders without disease progression will be censored at 
the censoring time point for TTP. 
Time to response (TTR) is defined as the time between the date of first dose and the 
first documented evidence of response (PR or better). Subjects without confirmed 
response (PR or better) will be censored at the censoring date for TTP. 
Progression-free survival (PFS) is defined as the time from first dose until the earliest 
date of disease progression (PD) per IMWG, or death due to any cause. Determination of 
dates of PFS event and dates for censoring will be described in the RAP. 
For all the TTE endpoints described above, median TTE with 95% CI will be estimated 
employing the Kaplan-Meier method as data permits. A Kaplan-Meier survival curve will 
be generated. The number and percentage of subjects who had the event or were censored 
will also be reported.
Exploratory subgroup analyses may be performed for all endpoints to measure clinical 
activity as appropriate.
Overall Survival: The protocol is amended to collect long-term survival data (i.e. up to 1 
year after last subject completes or discontinues treatment). Subjects who have already 
completed the study will be contacted to request re-consent.
If all the patients (who were alive at the time of study completion) can be re-consented, 
OS landmark analysis may be performed at 9 and 12 months using Kaplan-Meier analysis 
as data permits.
Otherwise, only descriptive analysis (number and % of deaths and lost to follow-up) will 
be performed.
13.7.8.
Health Outcome Analyses
Symptom impact and HRQoL will be assessed using the e-Diary. Change from baseline 
and change over time will be summarized. 
The calculation of scores and methods to deal with missing data will be provided in the 
RAP.
Visual Functioning Questionnaire (NEI VFQ-25 and OSDI): Data will be collected from 
end of treatment (EOT) visit as baseline. Additional data will be collected in follow-up 
visits on a monthly basis for subjects with ongoing corneal events or signs at EOT for 1 
year or until resolution, whichever occurs first. These data will not be collected for 
subjects who already completed the treatment. Methods for calculation of scores will be 
provided in the RAP. Due to limited number of on-treatment subjects at the time of 
protocol amendment, only individual subject data will be presented.


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14.
STUDY CONDUCT CONSIDERATIONS
14.1.
Posting of Information on Clinicaltrials.gov
Study information from this protocol will be posted on publicly available clinical trial 
registers before enrolment of subjects begins.
14.2.
Regulatory and Ethical Considerations, Including the 
Informed Consent Process
Prior to initiation of a study site, GSK will obtain approval from the appropriate 
regulatory agency to conduct the study in accordance with International Conference on 
Harmonization Good Clinical Practice (ICH GCP) and applicable country-specific 
regulatory requirements.
The study will be conducted in accordance with all applicable regulatory requirements.
The study will be conducted in accordance with ICH GCP, all applicable subject privacy 
requirements, and the ethical principles that are outlined in the Declaration of Helsinki 
2008, including, but not limited to:

Institutional review board (IRB)/ethics committee (EC) review and approval of study 
protocol and any subsequent amendments

Subject informed consent

Investigator reporting requirements
GSK will provide full details of the above procedures, either verbally, in writing, or both.
Written informed consent must be obtained from each subject prior to participation in the 
study.
14.3.
Urgent Safety Measures
If an event occurs that is related to the conduct of the study or the development of the IP, 
and this new event is likely to affect the study of subjects, the Sponsor, and the 
investigator will take appropriate urgent safety measures to protect subjects against any 
immediate hazard.
The Sponsor will work with the investigator to ensure the Institutional review board 
(IRB)/ethics committee (EC) is notified.
14.4.
Quality Control (Study Monitoring)
In accordance with applicable regulations, Good Clinical Practice (GCP) and GSK 
procedures, the site will be contacted prior to the start of the study to review with the site 
staff the protocol, study requirements, and their responsibilities to satisfy regulatory, 
ethical, and GSK requirements.  When reviewing data collection procedures, the 
discussion will include identification, agreement and documentation of data items for 
which the electronic case report form (eCRF) will serve as the source document.


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The investigator and the head of the medical institution (where applicable) agrees to 
allow the monitor direct access to all relevant documents and to allocate their time and 
the time to their staff to monitor to discuss findings and any issues.
Monitoring visits will be conducted in a manner to ensure that the:

Data are authentic, accurate, and complete.

Safety and rights of subjects are being protected.

Study is conducted in accordance with the currently approved protocol and any other 
study agreements, ICH GCP, and all applicable regulatory requirements.
14.5.
Quality Assurance
To ensure compliance with International Conference on Harmonization Good Clinical 
Practice (ICH GCP) and all applicable regulatory requirements, GSK may conduct 
quality assurance audits of the site.  Regulatory agencies may conduct a regulatory 
inspection at any time during or after completion of the study.  In the event of an audit or 
inspection, the investigator (and institution) must agree to grant the auditor(s) and 
inspector(s) direct access to all relevant documents and to allocate their time and the time 
of their staff to discuss any findings/relevant issues.
14.6.
Study and Site Closure
The end of the study will be defined as the date of the last visit of the last subject 
enrolled.
Upon completion or termination of the study, the monitor will conduct site closure 
activities with the investigator or site staff (as appropriate), in accordance with applicable 
regulations, International Conference on Harmonization Good Clinical Practice (ICH 
GCP), and GSK Standard Operating Procedures.
GSK reserves the right to temporarily suspend or terminate the study at any time for 
reasons including (but not limited to) safety issues, ethical issues, or severe 
noncompliance.  If GSK determines that such action is required, GSK will discuss the 
reasons for taking such action with the investigator or head of the medical institution 
(where applicable).  When feasible, GSK will provide advance notice to the investigator 
or head of the medical institution of the impending action.
If a study is suspended or terminated for safety reasons, GSK will promptly inform all 
investigators, heads of the medical institutions (where applicable),and/or institutions 
conducting the study.  GSK will also promptly inform the relevant regulatory authorities 
of the suspension/termination along with the reasons for such action.  Where required by 
applicable regulations, the investigator or head of the medical institution must inform the 
IRB/EC promptly and provide the reason(s) for the suspension/termination.
GSK may also close study sites which fail to recruit subjects within a predefined 
timeframe, as defined within the Study Procedures Manual (SPM).


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14.7.
Records Retention
Following closure of the study, the investigator or head of the medical institution (where 
applicable) must maintain all site study records (except for those required by local 
regulations to be maintained elsewhere) in a safe and secure location.  The records must 
be easily accessible when needed (e.g., for a GSK audit or regulatory inspection) and 
must be available for review in conjunction with assessment of the facility, supporting 
systems, and relevant site staff.
Where permitted by local laws/regulations or institutional policy, some or all of the 
records may be maintained in a format other than hard copy (e.g., microfiche, scanned, 
electronic); however, caution must be exercised before such action is taken.  The 
investigator must ensure that all reproductions are legible and are a true and accurate 
copy of the original.  In addition, they must meet accessibility and retrieval standards, 
including regeneration of a hard copy, if required.  The investigator must also ensure that 
an acceptable back-up of the reproductions exists and that there is an acceptable quality 
control procedure in place for creating the reproductions.
GSK will inform the investigator of the time period for retaining the site records in order 
to comply with all applicable regulatory requirements.  The minimum retention time will 
meet the strictest standard applicable to a particular site, as dictated by local 
laws/regulations, GSK standard operating procedures, and/or institutional requirements.
The investigator must notify GSK of any changes in the archival arrangements, including, 
but not limited to archival of records at an off-site facility or transfer of ownership of the 
records in the event that the investigator is no longer associated with the site.
14.8.
Provision of Study Results to Investigators, Posting of 
Information on Publicly Available Clinical Trials Registers 
and Publication
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 subjects, as 
appropriate.
The results summary will be posted to the GSK Clinical Study Register no later than 
eight months after the final primary completion date, the date that the final subject was 
examined or received an intervention for the purposes of final collection of data for the 
primary outcome.  In addition, a manuscript will be submitted to a peer reviewed journal 
for publication no later than 18 months after the last subject’s last visit (LSLV).  When 
manuscript publication in a peer reviewed journal is not feasible, a statement will be 
added to the register to explain the reason for not publishing.


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15.
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Palumbo A and Anderson K. Multiple Myeloma. N Engl J Med. 2011; 364:1046-60. 
Papay JI, Clines D, Rafi R, Yuen N, Britt SD, Walsh JS, et al. Drug-induced liver injury 
following positive drug rechallenge. Regul Toxicol Pharmacol 2009;54:84-90. 
Rajkumar SV. Multiple myeloma: 2011 update on diagnosis, risk stratification, and 
management. Am J Hematol. 2011b;86:57-65. 
Rajkumar SV. Treatment of multiple myeloma. Nat Rev Clin Oncol. 2011a;8:479-491. 
Sanchez E, Li M, Kitto A, Li J, Wang SJ, Kirk DT, et al. Serum B-cell maturation 
antigen is elevated in multiple myeloma and correlates with disease status and survival. 
Brit J Haematol. 2012;158:727-738. 
Schiffman, R. M., M. D. Christianson, G. Jacobsen, J. D. Hirsch and B. L. Reis . 
"Reliability and validity of the Ocular Surface Disease Index." Arch Ophthalmol. 2000; 
118(5): 615-621. 
Sullivan P and Salmon S. Kinetics of Tumor Growth and Regression in IgG Multiple 
Myeloma. J Clin Investigation, 1972, 51: 1697-1708. 
Thompson, J, Forero A, Heath E, Pal S, Ansell S, Infante J, et al.  SGN-75 in the 
treatment of patients with CD70-positive malignancies including metastatic renal cell 
carcinoma. J Clin Oncol 2013;31 (suppl 6; abstr 368). 
Tomoyuki E, Mitsufumi N, Enzler T, Cottam H, Fukuda T, James D, et al.  BAFF and 
APRIL support chronic lymphocytic leukemia B-cell survival through activation of the 
canonical NF-κB pathway.  Blood 2007:109:703-710. 
 
 
 


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16.
APPENDICES
16.1.
Appendix 1: International Myeloma Working Group Uniform
Response Criteria for Multiple Myeloma
Response
IMWG Criteria
sCR

CR as defined below plus normal FLC ratio and absence of clonal
cells in bone marrow3 by immunohistochemistry or 
immunofluorescence4
CR

Negative immunofixation on the serum and urine and 
disappearance of any soft tissue plasmacytomas and < 5% plasma 
cells in bone marrow3
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/24 h
PR

≥ 50% reduction of serum M-protein and reduction in 24 hours 
urinary M-protein by ≥90% or to < 200 mg/24 h

If the serum and urine M-protein are unmeasurable,5 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 not measurable, and serum free 
light assay is also not measureable, ≥ 50% reduction in plasma cells 
is required in place of M-protein, provided baseline bone marrow 
plasma cell percentage was ≥ 30%

In addition to the above listed criteria, if present at baseline, a ≥ 
50% reduction in the size of soft tissue plasmacytomas is also 
required
MR

25% but <49% reduction of serum M protein and reduction in 24 
hour urine M protein by 50-89%, which still exceeds 200 mg per 24 
hour

In addition to the above criteria, if present at baseline, 25-49% 
reduction in the size of soft tissue plasmacytomas is also required

No increase in size or number of lytic bone lesions (development of 
compression fracture does not exclude response)
No 
change/Stable 
disease

Not meeting criteria for CR, VGPR, PR, or progressive disease
Progressive 
Disease

Increase of ≥ 25% from lowest response value in any one or more 
of the following:
o
Serum M-component and/or (the absolute increase must be 
≥ 0.5 g/dL)6
o
Urine M-component and/or (the absolute increase must be 
≥200 mg/24 h)


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Response
IMWG Criteria

Only in patients without measurable serum and urine M-protein 
levels; the difference between involved and uninvolved FLC levels. 
The absolute increase must be > 10 mg/dL

Bone marrow plasma cell percentage; the absolute percentage must 
be ≥ 10%7

Definite development of new bone lesions or soft tissue 
plasmacytomas or definite increase in the size of existing bone 
lesions or soft tissue plasmacytomas

Development of hypercalcaemia (corrected serum calcium > 11.5 
mg/dL or 2.65mmol/L) that can be attributed solely to the plasma 
cell proliferative disorder
Relapse
Clinical relapse requires one or more of:

Direct indicators of increasing disease and/or end organ dysfunction 
(CRAB features).6 It is not used in calculation of time to 
progression or progression-free survival but is listed here as 
something that can be reported optionally or for use in clinical 
practice

Development of new soft tissue plasmacytomas or bone lesions

Definite increase in the size of existing plasmacytomas or bone 
lesions. A definite increase is defined as a 50% (and at least 1 cm) 
increase as measured serially by the sum of the products of the 
cross-diameters of the measurable lesion

Hypercalcemia (> 11.5 mg/dL) [2.65 mmol/L]

Decrease in haemoglobin of ≥ 2 g/dL [1.25 mmol/L]

Rise in serum creatinine by 2 mg/dL or more [177 mol/L or more]
Relapse from 
CR5 (to be 
used only if 
the endpoint 
studied is 
DFS)8
Any one or more of the following:

Reappearance of serum or urine M-protein by immunofixation or 
electrophoresis

Development of ≥ 5% plasma cells in the bone marrow7

Appearance of any other sign of progression (i.e., new 
plasmacytoma, lytic bone lesion, or hypercalcaemia)
Overall Responders:  PR, VGPR, CR, sCR
Clinical Benefit Rate:  Overall responders + MR
Adapted from Durie BGM, et al. Leukemia 2006; 20: 1467-1473; and Kyle RA, 
Rajkumar SV. Leukemia
2008;23:3-9.
Note: A clarification to IMWG criteria for coding CR and VGPR in patients in whom the 
only measurable
disease is by serum FLC levels: CR in such patients is defined as a normal FLC ratio of 
0.26–1.65 in
addition to CR criteria listed above. VGPR in such patients is defined as a >90% decrease 
in the difference
between involved and uninvolved free light chain (FLC) levels.
3 Confirmation with repeat bone marrow biopsy not needed.


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4 Presence/absence of clonal cells is based upon the kappa/lambda ratio. An abnormal 
kappa/lambda ratioby immunohistochemistry and/or immunofluorescence requires a 
minimum of 100 plasma cells foranalysis. An abnormal ratio reflecting presence of an 
abnormal clone is kappa/lambda of > 4:1 or < 1:2.
5 All relapse categories require two consecutive assessments made at any time before 
classification as relapse or disease progression and/or the institution of any new therapy. 
In the IMWG criteria, CR patients must also meet the criteria for progressive disease 
shown here to be classified as progressive disease for the purposes of calculating time to 
progression and progression-free survival. The definitions of relapse, clinical relapse and 
relapse from CR are not to be used in calculation of time to progression or progression 
free survival
6 For progressive disease, serum M-component increases of ≥1 gm/dL are sufficient to 
define relapse if starting M-component is ≥5 g/dL.
7 Relapse from CR has the 5% cut-off versus 10% for other categories of relapse.
8 For purposes of calculating time to progression and progression-free survival, CR 
patients should also be evaluated using criteria listed above for progressive disease.


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16.2.
Appendix 2: Revised Response Criteria for Malignant 
Lymphoma
Response Criteria for Malignant Lymphoma
Response
Definition
Nodal Masses
Spleen, Liver
Bone Marrow
CR
Disappearance of 
all evidence of 
disease
(a). FDG-avid or 
PET positive prior 
to therapy; mass 
of any size 
permitted if PET 
negative
(b). Variably 
FDG-avid or Pet 
negative; 
regression to 
normal size on CT
Not palpable, 
nodules 
disappeared
Infiltrate cleared on 
repeat biopsy; if 
indeterminate by 
morphology, 
immunohistochemistry 
should be negative
PR
Regression of 
measurable 
disease and no 
new sites
50% decrease in 
SPD of up to 6 
largest dominant 
masses; no 
increase in size of 
other nodes
(a). FDG-avid or 
PET positive prior 
to therapy; one or 
more PET 
positive at 
previously 
involved site
(b). Variably 
FDG-avid or PET 
negative; 
regression on CT
50% decrease 
in SPD of 
nodules (for 
single nodule 
in greatest 
transverse 
diameter); no 
increase in size 
of liver or 
spleen
Irrelevant if positive 
prior to therapy; cell 
type should be 
specified
SD
Failure to attain 
CR/PR or PD
(a). FDG-avid or 
PET positive prior 
to therapy; PET 
positive at prior 
sites of disease 
and no new sites 
on CT or PET
(b). Variably 
FDG-avid or PET 
negative; no 
change in size of 
previous lesions 
on CT


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Response Criteria for Malignant Lymphoma
Response
Definition
Nodal Masses
Spleen, Liver
Bone Marrow
Relapsed 
Disease or 
PD
Any new lesion 
or increase by 
50% of 
previously 
involved sites 
from nadir
Appearance of a 
new lesion(s) >1.5 
cm in any axis, 
50% increase in 
SPD of more than 
one node, or 
50% increase in 
longest diameter 
of a previously 
identified node >1 
cm in short axis
Lesions PET 
positive if FDG-
avid lymphoma or 
Pet positive prior 
to therapy
>50% increase 
from nadir in 
the SPD or any 
previous 
lesions
New or recurrent 
involvement
Abbreviations: CR = complete remission; FDG = [18F]fluorodeoxyglucose; PET = 
positron emission tomography; CT = computed tomography; PR = partial remission; SPD 
= sum of the product of the diameters; SD = stable disease; PD = progressive disease


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16.3.
Appendix 4: NYHA Functional Classification System
The New York Heart Association (NYHA) Functional Classification: Class I, II, III 
or IV Heart Failure [NYHA, 1994] provides a simple way of classifying the extent of 
heart failure.  It places subjects in one of 4 categories based on the level of limitation 
experienced during physical activity:
Class
Symptoms
Class I
(Mild)
No limitation of physical activity.  Ordinary physical activity does 
not cause undue fatigue, palpitation or dyspnea (shortness of 
breath).
Class II
(Mild)
Slight limitation of physical activity.  Comfortable at rest, but 
ordinary physical activity results in fatigue, palpitation or dyspnea.
Class III
(Moderate)
Marked limitation of physical activity.  Comfortable at rest, but less 
than ordinary physical activity results in fatigue, palpitation or 
dyspnea.
Class IV
(Severe)
Unable to carry out any physical activity without discomfort.  
Symptoms of cardiac insufficiency at rest.  If any physical activity is 
undertaken, discomfort is increased.
Reference:
The Criteria Committee of the New York Heart Association (NYHA).  Nomenclature and 
Criteria for Diagnosis of Diseases of the Heart and Great Vessels. 9th Ed. Boston, Mass:  
Little, Brown & Co.;  1994:253-256.


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16.4.
Appendix 5: Modified Diet in Renal Disease Formula
MDRD
eGFR = 175 × (Scr)-1.154 × (Age)-0.203 × (0.742 if female) × (1.212 if 
African American)
GFR is expressed in mL/min/1.73 m2, SCr is serum creatinine 
expressed in mg/dL, and age is expressed in years.
The link below will auto-calculate the creatinine clearance:
http://nephron.org/cgi-bin/MDRD_GFR/cgi


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16.5.
Appendix 6: ECOG Performance Status1
Grade
Descriptions
0
Normal activity.  Fully active, able to carry on all pre-disease performance 
without restriction.
1
Symptoms, but ambulatory.  Restricted in physically strenuous activity, but 
ambulatory and able to carry out work of a light or sedentary nature (e.g., 
light housework, office work).
2
In bed <50% of the time.  Ambulatory and capable of all self-care, but 
unable to carry out any work activities.  Up and about more than 50% of 
waking hours.
3
In bed >50% of the time.  Capable of only limited self-care, confined to 
bed or chair more than 50% of waking hours.
4
100% bedridden.  Completely disabled.  Cannot carry on any self-care.  
Totally confined to bed or chair.
5
Dead.
1.
[Oken, 1982]
Reference:
Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., Davis, T.E., McFadden, E.T., 
Carbone, P.P.: Toxicity And Response Criteria Of The Eastern Cooperative Oncology 
Group. Am J Clin Oncol 5:649-655, 1982.


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16.6.
Appendix 7: Genetics
Genetics – Background
Naturally occurring genetic variation may contribute to inter-individual variability in 
response to medicines, as well as an individual's risk of developing specific diseases. 
Genetic factors associated with disease characteristics may also be associated with 
response to therapy, and could help to explain some clinical study outcomes. For
example, genetic variants associated with age-related macular degeneration (AMD) are 
reported to account for much of the risk for the condition [Gorin, 2012] with certain 
variants reported to influence treatment response [Chen, 2012]. Thus, knowledge of the 
genetic etiology of disease may better inform understanding of disease and the 
development of medicines. Additionally, genetic variability may impact the 
pharmacokinetics (absorption, distribution, metabolism, and elimination), or 
pharmacodynamics (relationship between concentration and pharmacologic effects or the 
time course of pharmacologic effects) of a specific medicine and/or clinical outcomes 
(efficacy and/or safety) observed in a clinical study.
Genetic Research Objectives and Analyses
The objectives of the genetic research are to investigate the relationship between genetic 
variants and: 

Response to medicine, including GSK2857916 or any concomitant medicines;

Multiple myeloma and lymphomas expressing BCMA susceptibility, severity, and 
progression and related conditions
Genetic data may be generated while the study is underway or following completion of 
the study.  Genetic evaluations may include focused candidate gene approaches and/or 
examination of a large number of genetic variants throughout the genome (whole genome 
analyses). Genetic analyses will utilize data collected in the study and will be limited to 
understanding the objectives highlighted above.  Analyses may be performed using data 
from multiple clinical studies to investigate these research objectives.
Appropriate descriptive and/or statistical analysis methods will be used. A detailed 
description of any planned analyses will be documented in a Reporting and Analysis Plan 
(RAP) prior to initiation of the analysis. Planned analyses and results of genetic 
investigations will be reported either as part of the clinical RAP and study report, or in a 
separate genetics RAP and report, as appropriate.
Study Population
Any subject who is enrolled in part 2 (expansion cohort) of the clinical study can 
participate in genetic research.  Any subject who has received an allogeneic bone marrow 
transplant must be excluded from the genetic research.
Subject participation in the genetic research is voluntary and refusal to participate will 
not indicate withdrawal from the clinical study.  Refusal to participate will involve no 
penalty or loss of benefits to which the subject would otherwise be entitled.


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Study Assessments and Procedures
A key component of successful genetic research is the collection of samples during 
clinical studies. Collection of samples, even when no a priori hypothesis has been 
identified, may enable future genetic analyses to be conducted to help understand 
variability in disease and medicine response.  

A 6 ml blood sample will be taken for Deoxyribonucleic acid (DNA) extraction. 
A blood sample is collected at the baseline visit, after the subject has been 
randomized and provided informed consent for genetic research. Instructions for 
collection and shipping of the genetic sample are described in the laboratory 
manual. The DNA from the blood sample may undergo quality control analyses to 
confirm the integrity of the sample. If there are concerns regarding the quality of 
the sample, then the sample may be destroyed. The blood sample is taken on a 
single occasion unless a duplicate sample is required due to an inability to utilize 
the original sample.  
The genetic sample is labelled (or “coded”) with the same study specific number used to 
label other samples and data in the study.   This number can be traced or linked back to 
the subject by the investigator or site staff. Coded samples do not carry personal 
identifiers (such as name or social security number). 
Samples will be stored securely and may be kept for up to 15 years after the last subject 
completes the study, or GSK may destroy the samples sooner.  GSK or those working 
with GSK (for example, other researchers) will only use samples collected from the study 
for the purpose stated in this protocol and in the informed consent form.  Samples may be 
used as part of the development of a companion diagnostic to support the GSK medicinal 
product.
Subjects can request their sample to be destroyed at any time.
Informed Consent
Subjects who do not wish to participate in the genetic research may still participate in the 
study.  Genetic informed consent must be obtained prior to any blood being taken.
Subject Withdrawal from Study
If a subject who has consented to participate in genetic research withdraws from the 
clinical study for any reason other than being lost to follow-up, the subject will be given a 
choice of one of the following options concerning the genetic sample, if already 
collected:

Continue to participate in the genetic research in which case the genetic DNA 
sample is retained

Discontinue participation in the genetic research and destroy the genetic DNA 
sample 


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If a subject withdraws consent for genetic research or requests sample destruction for any 
reason, the investigator must complete the appropriate documentation to request sample 
destruction within the timeframe specified by GSK and maintain the documentation in 
the site study records. 
Genotype data may be generated during the study or after completion of the study and 
may be analyzed during the study or stored for future analysis. 

If a subject withdraws consent for genetic research and genotype data has not been 
analyzed, it will not be analyzed or used for future research.  

Genetic data that has been analyzed at the time of withdrawn consent will 
continue to be stored and used, as appropriate. 
Screen and Baseline Failures
If a sample for genetic research has been collected and it is determined that the subject 
does not meet the entry criteria for participation in the study, then the investigator should 
instruct the subject that their genetic sample will be destroyed. No forms are required to 
complete this process as it will be completed as part of the consent and sample 
reconciliation process.  In this instance a sample destruction form will not be available to 
include in the site files.
Provision of Study Results and Confidentiality of Subject’s Genetic Data
GSK may summarize the genetic research results in the clinical study report, or 
separately and may publish the results in scientific journals. 
GSK may share genetic research data with other scientists to further scientific 
understanding in alignment with the informed consent. GSK does not inform the subject, 
family members, insurers, or employers of individual genotyping results that are not 
known to be relevant to the subject’s medical care at the time of the study, unless 
required by law. This is due to the fact that the information generated from genetic 
studies is generally preliminary in nature, and therefore the significance and scientific 
validity of the results are undetermined.  Further, data generated in a research laboratory 
may not meet regulatory requirements for inclusion in clinical care.
References
Chen H, Yu KD, Xu GZ. Association between Variant Y402H in Age-Related Macular 
Degeneration (AMD) Susceptibility Gene CFH and Treatment Response of AMD: A 
Meta-Analysis. PloS ONE 2012; 7: e42464
Gorin MB. Genetic insights into age-related macular degeneration: Controversies 
addressing risk, causality, and therapeutics. Mol. Asp. Med. 2012; 33: 467-486.


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16.7.
Appendix 8: Liver Safety Drug Restart Guidelines
Drug restart may be considered for a subject exhibiting compelling benefit for a critical 
medicine following drug-induced liver injury, if there is favorable benefit: risk ratio and 
no alternative medicine available.
Background Information on Drug Restart/Rechallenge
Following drug-induced liver injury, drug restart or rechallenge is associated with a 
13% mortality across all drugs in prospective studies.1  Clinical outcomes vary by 
drug, with nearly 50% fatality with halothane readministered in one month of initial 
injury. However, some drugs seldom result in recurrent liver injury or fatality.  Risk 
factors for a fatal drug restart/rechallenge outcome include: hypersensitivity1 with initial 
liver injury (e.g. fever, rash, eosinophilia), jaundice or bilirubin 2xULN or INR>1.5 
suggesting severe liver injury, prior IP-related severe or fatal drug restart/rechallenge2,3 or 
evidence of drug-related preclinical liability / mitochondrial impairment3.
Drug Restart/Rechallenge Process (also see Figure 1)
6.
Principal Investigator (PI) requests consideration of drug restart for a subject 
receiving compelling benefit from a critical or life-saving drug, who exhibits liver 
chemistry elevation meeting subject stopping criteria, with no alternative 
treatment.
GSK Medical Monitor & Clinical Safety Physician.to review the subject’s 
restart/rechallenge risk factors & complete checklist (Table 18).
Table 18
Checklist for drug restart/rechallenge for critical medicine
(Following drug-induced liver injury, drug rechallenge is associated with 13% mortality 
across all drugs in prospective studies)
Yes
No
Compelling benefit of the investigational product (IP) for this subject 
and no alternative therapy.  Provide brief explanation:
Relative benefit-risk favorable for drug restart/rechallenge, after 
considering the following high risk factors:
•
Initial liver injury event included: 
–
fever, rash, eosinophilia, or hypersensitivity
–
or bilirubin 2xULN (direct bilirubin >35% of total)
•
Subject currently exhibits ALT 3xULN, bilirubin 2xULN (direct 
bilirubin >35% of total), or INR1.5
•
Severe or fatal restart/rechallenge has earlier been observed 
with IP If yes, please provide brief explanation:
•
IP associated with known preclinical hepatic liability/ injury 


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If GSK provides written approval for restart/rechallenge following the above review, 
the Principal Investigator (PI) must ensure the following:

The PI is to obtain Ethics Committee or Institutional Review Board review of 
drug re-initiation, as required. 

PI must discuss the possible benefits and risks of drug re-initiation with the 
subject.

The subject must sign informed consent with a clear description of possible 
benefits and risks of drug administration, including recurrent liver injury or death. 
Consent specifically for the IP restart must be recorded in the study chart.

The drug must be reinitiated at GSK approved dose(s). 

Subjects approved by GSK for restart of IP must return to the clinic twice a week 
for liver chemistry tests until stable, liver chemistries have been demonstrated and 
then laboratory monitoring may resume as per protocol.  If protocol defined 
stopping criteria for liver chemistry elevations are met, study drug must be 
stopped.

The Ethics Committee or Institutional Review Board is to be informed of the 
subject’s outcome, as required.

GSK is to be notified of any adverse events, as per Section 8.5.2.


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References:
Andrade RJ, Robles M, Lucena MI. Rechallenge in drug-induced liver injury:the 
attractive hazard. Expert Opin Drug Saf 2009;8:709–714.
Hunt CM. Mitochondrial and immunoallergic injury increase risk of positive drug 
rechallenge after drug-induced liver injury: a systematic review. Hepatology 
2010;52:2216–2222
Papay JI, Clines D, Rafi R, Yuen N, Britt SD, Walsh JS, et al. Drug-induced liver injury 
following positive drug rechallenge. Regul Toxicol Pharmacol 2009;54:84-90.


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16.8.
Appendix 9: Urine Protein Creatinine (UPC) Ratio Clinical 
meaning of UPC
There is a good correlation between the ratio of protein concentration to creatinine 
concentration in a random urine sample and the amount of protein excreted over 
24 hours.  Creatinine excretion is fairly constant throughout the day regardless of changes 
in urine flow rate.
Normal protein excretion is <150 mg/24 hours and is similar for men and women.
Men excrete 20 mg to 25 mg of creatinine/kg of body weight/day.
Women excrete 15 mg to 20 mg of creatinine/kg of body weight/day.
Calculating UPC
UPC ratio = Urine protein (mg/dL) / Urine creatinine (mg/dL). 
UPC ratio ≈equivalent to grams of protein excreted in urine over 24 hrs. 
Example:  Patient has a urine protein = 90 mg/dL and urine creatinine = 30 mg/dL.  
UPC ratio= (90 mg/dL) / (30 mg/dL) =  3  
The calculated UPC ratio is 3, which correlates to roughly 3 g protein excretion in a 24-
hour period.
Units for UPC ratio
Note: To calculate UPC, protein and creatinine concentrations must be expressed in the 
same units (mg/dL, g/L, or μmol/L). If, for example, protein concentration is expressed 
in mg/dL and creatinine concentration is expressed in µmol/L, conversion of one of the 
concentration values is required.  Conversion factors are: 
From 
To 
Conversion Factor 
Conventional Units: mg/dL
SI Units: µmol/L
Multiply by 88.4
SI Units: µmol/L
Conventional Units: mg/dL
Divide 88.4 
References:
NKF: NKF KDOQI Guidelines [Internet].  National Kidney Foundation; nd.  KDOQI 
Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and 
Stratification.  Available from 
http://www.kidney.org/professionals/KDOQI/guidelines_ckd/p5_lab_g5.htm
Xin G, Wang M, Jian L, Xu F, Wang H.  Protein-to-creatinine ratio in spot urine samples 
as a predictor of quantitation of proteinuria 2004. Clinica Chimica Acta 350:35-39.


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16.9.
Appendix 10: Blood Requirements
16.9.1.
Blood Requirements for All Lab Tests, Except PK
16.9.1.1.
Dose Escalation: Every 3 Weeks for Multiple Myeloma
Test Sample
Sample 
Volume
Screening
Cycle 1
Each 
Subsequent 
Cycle
Hematology
5 ml
5 ml
10-15 ml
5 ml
Chemistry
5 ml
5 ml
15-20 ml
5 ml
Coagulation
5 ml
5 ml
10-15 ml
5 ml
SPEP
6 ml
6 ml
6 ml
CRP
1 ml
1 ml
1 ml
B2 Microglobulin
1 ml
1 ml
1 ml
Kappa, lambda 
free LC, FLC
1 ml
1 ml
1 ml
IgG, IgA, IgM
6 ml
6 ml
6 ml
cfDNA
10 ml
10 ml
Cytokines
3 ml
6 ml
6 ml
HBV/HCV
3 ml
3 ml
CK-MB
3 ml
3 ml
3 ml
3 ml
ADA
3 ml
3 ml
0-3 ml
BNP
3 ml
3 ml
Troponin
2.5 ml
2.5 ml
2.5 ml
2.5 ml
TBNK
3 ml
3 ml
3 ml
sBCMA
1 ml
5 ml
1-2 ml
Pregnancy Test1
2 ml
2 ml
0-2 ml
Total
59.5 ml
51.5-66.5 ml
45.5-51.5 ml
1. Required for women of childbearing potential
16.9.1.2.
Dose Escalation:  Weekly for Multiple Myeloma
Test Sample
Sample 
Volume
Screening
Cycle 1
Each 
Subsequent 
Cycle
Hematology
5 ml
5 ml
10-15 ml
5 ml
Chemistry
5 ml
5 ml
15-20 ml
5 ml
Coagulation
5 ml
5 ml
10-15 ml
5 ml
SPEP
6 ml
6 ml
6 ml
CRP
1 ml
1 ml
1 ml
1 ml
B2 Microglobulin
1 ml
1 ml
1 ml
1 ml
Kappa, lambda free 
LC, FLC
1 ml
1 ml
1 ml
IgG, IgA, IgM
6 ml
6 ml
6 ml
cfDNA
10 ml
10 ml


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Test Sample
Sample 
Volume
Screening
Cycle 1
Each 
Subsequent 
Cycle
Cytokines
3 ml
6 ml
6 ml
HBV/HCV
3 ml
3 ml
CK-MB
3 ml
3 ml
3 ml
3 ml
ADA
3 ml
3 ml
0-3 ml
BNP
3 ml
3 ml
Troponin
2.5 ml
2.5 ml
2.5 ml
2.5 ml
TBNK
6 ml
6 ml
6 ml
sBCMA
1 ml
6 ml
1-2 ml
Pregnancy Test1
2 ml
2 ml
0-2 ml
Total
43.5 ml
73.5-88.5 ml
48.5-54.5 ml
1. Required for women of childbearing potential
16.9.1.3.
Dose Expansion:  Every 3 Weeks for Multiple Myeloma
Test Sample
Sample 
Volume
Screening
Cycle 1
Each 
Subsequent 
Cycle
Hematology
5 ml
5 ml
10-15 ml
5 ml
Chemistry
5 ml
5 ml
10-15 ml
5 ml
Coagulation
5 ml
5 ml
10-15 ml
5 ml
SPEP
6 ml
6 ml
6 ml
CRP
1 ml
1 ml
1 ml
B2 Microglobulin
1 ml
1 ml
1 ml
Kappa, lambda free 
LC, FLC
1 ml
1 ml
1 ml
IgG, IgA, IgM
6 ml
6 ml
6 ml
cfDNA
10 ml
10 ml
Cytokines
3 ml
6 ml
6 ml
HBV/HCV
3 ml
3 ml
CK-MB
3 ml
3 ml
3 ml
3 ml
ADA
3 ml
3 ml
0-3 ml
BNP
3 ml
3 ml
Troponin
2.5 ml
2.5 ml
2.5 ml
2.5 ml
TBNK
6 ml
6 ml
6 ml
sBCMA
1 ml
2 ml
1-2 ml
Pregnancy Test1
2 ml
2 ml
0-2 ml
Genetics Sample
6 ml
6 ml
Total
43.5 ml
68.5-83.5 ml
48.5-54.5 ml
1. Required for women of childbearing potential


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16.9.1.4.
Dose Expansion:  Weekly for Multiple Myeloma
Test Sample
Sample 
Volume
Screening
Cycle 1
Each 
Subsequent 
Cycle
Hematology
5 ml
5 ml
10-15 ml
5 ml
Chemistry
5 ml
5 ml
10-15 ml
5 ml
Coagulation
5 ml
5 ml
10-15 ml
5-10 ml
SPEP
6 ml
6 ml
6 ml
CRP
1 ml
1 ml
1 ml
B2 Microglobulin
1 ml
1 ml
1 ml
Kappa, lambda free 
LC, FLC
1 ml
1 ml
1 ml
IgG, IgA, IgM
6 ml
6 ml
6 ml
cfDNA
10 ml
10 ml
Cytokines
3 ml
6 ml
6 ml
HBV/HCV
3 ml
3 ml
CK-MB
3 ml
3 ml
3 ml
3 ml
ADA
3 ml
3 ml
0-3 ml
BNP
3 ml
3 ml
Troponin
2.5 ml
2.5 ml
2.5 ml
2.5 ml
TBNK
6 ml
6 ml
6 ml
sBCMA
1 ml
1 ml
1-2 ml
Pregnancy Test1
2 ml
2 ml
0-2 ml
Genetics Sample
6 ml
6 ml
Total
43.5 ml
68.5-83.5 ml
48.5-59.5 ml
1. Required for women of childbearing potential
16.9.1.5.
Dose Expansion:  Every 3 Weeks for Lymphomas
Test Sample
Sample 
Volume
Screening
Cycle 1
Each 
Subsequent 
Cycle
Hematology
5 ml
5 ml
10-15 ml
5 ml
Chemistry
5 ml
5 ml
10-15 ml
5 ml
Coagulation
5 ml
5 ml
10-15 ml
5 ml
CRP
1 ml
1 ml
1 ml
B2 Microglobulin
1 ml
1 ml
1 ml
IgG, IgA, IgM
6 ml
6 ml
6 ml
cfDNA
10 ml
10 ml
Cytokines
3 ml
6 ml
6 ml
HBV/HCV
3 ml
3 ml
CK-MB
3 ml
3 ml
3 ml
3 ml
ADA
3 ml
3 ml
0-3 ml
BNP
3 ml
3 ml
Troponin
2.5 ml
2.5 ml
2.5 ml
2.5 ml
TBNK
6 ml
6 ml
6 ml


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Test Sample
Sample 
Volume
Screening
Cycle 1
Each 
Subsequent 
Cycle
sBCMA
1 ml
1 ml
0-2 ml
Pregnancy Test1
2 ml
2 ml
0-2 ml
Genetics Sample
6 ml
6 ml
Total
36.5 ml
67.5-82.5 ml
40.5-47.5 ml
1. Required for women of childbearing potential
16.9.1.6.
Dose Expansion:  Weekly for Lymphomas
Test Sample
Sample 
Volume
Screening
Cycle 1
Each 
Subsequent 
Cycle
Hematology
5 ml
5 ml
10-15 ml
5 ml
Chemistry
5 ml
5 ml
10-15 ml
5-10 ml
Coagulation
5 ml
5 ml
10-15 ml
5 ml
CRP
1 ml
1 ml
1 ml
B2 Microglobulin
1 ml
1 ml
1 ml
IgG, IgA, IgM
6 ml
6 ml
6 ml
cfDNA
10 ml
10 ml
Cytokines
3 ml
6 ml
6 ml
HBV/HCV
3 ml
3 ml
CK-MB
3 ml
3 ml
3 ml
3 ml
ADA
3 ml
3 ml
0-3 ml
BNP
3 ml
3 ml
Troponin
2.5 ml
2.5 ml
2.5 ml
2.5 ml
TBNK
6 ml
6 ml
6 ml
sBCMA
1 ml
5 ml
0-2 ml
Pregnancy Test1
2 ml
2 ml
0-2 ml
Genetics Sample
6 ml
6 ml
Total
36.5 ml
74.5-89.5 ml
40.5-51.5 ml
1. Required for women of childbearing potential
16.9.2.
Blood Requirements for PK
PK Schedule
Sample 
Volume
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 5 
Total 
Volume
Escalation Every 3 Weeks
5 ml
60 ml
10 ml
10 ml
80 ml
Escalation Weekly
5 ml
80 ml
10ml
10 ml
100 ml
Expansion Every 3 Weeks 
MM
5 ml
20 ml
20 ml
20 ml
20 ml
80 ml
Expansion Weekly MM
5 ml
20 ml
10 ml
10 ml
10 ml
50 ml
Expansion Every 3 Weeks 
Lymphomas
5 ml
40 ml
20 ml
20 ml
10 ml
90 ml
Expansion Weekly 
Lymphomas
5 ml
40 ml
20 ml
20 ml
10 ml
90 ml


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16.9.3.
Total Blood Requirements
Schedule
Screening
Cycle 1
Each Subsequent 
Cycle
Escalation Every 3 Weeks 
MM
59.5 ml
51.5-66.5 ml
45.5-51.5 ml
Escalation Weekly MM
43.5 ml
73.5-88.5 ml
48.5-54.5 ml
Expansion Every 3 Weeks 
MM
43.5 ml
68.5-83.5 ml
48.5-54.5 ml
Expansion Weekly MM
43.5 ml
68.5-83.5 ml
48.5-59.5 ml
Expansion Every 3 Weeks 
Lymphomas
36.5 ml
67.5-82.5 ml
40.5-47.5 ml
Expansion Weekly 
Lymphomas
36.5 ml
74.5-89.5 ml
40.5-51.5 ml
The Study Procedures Manual will be updated with new information if changes in blood 
volumes are required.


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16.10.
Appendix 11:  Pgp Inhibitors
Amiodarone
Atorvastatin
Azithromycin
Carvedilol
Clarithromycin
Dronedarone
Fluvoxamine
Indinavir
Indinavir and Ritonavir
Itraconazole
Ketonazole
Lapatinib
Lopinavir and Ritonavir
Nicardipine
Quinidine
Ranolazine
Ritonavir
Saquinavir and Ritonavir
Telaprevir
Verapamil
Valspodar
The Study Procedures Manual will be updated if changes to the Pgp inhibitor list is 
required.


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16.11.
Appendix 12: Protocol Amendment Changes
16.11.1.
Amendment 1
Where the Amendment Applies
United Kingdom
Summary of Amendment Changes with Rationale
1. Regulatory Agency Identifying Number(s): Corrected EudraCT Number

Rationale:  Typographical error corrected.
2. Protocol Synopsis, Exclusion Criteria, page 25; Section 5.2.2, Exclusion Criteria, 
page 85: Added #18

Rationale: MHRA requested the exclusion of subjects with current or history 
of corneal pathology given the corenal necrosis seen in rat studies.
3. Section 3.3, Part 1: Dose-Escalation Phase, page 47; Section 3.3.1.2.1, Planned 
Dose Levels, pages 50 and 51; Section 3.3.3, Dose-Limiting Toxicity – Part 1 
only, page 54; Section 3.4, RP2 Dose and Administration Schedule Selection for 
Part 2, page 56: Added reference to new Section 12.1, Data Dissemination and 
Communication Plan.

Rationale:  References to new section on data dissemination and 
communication to sites requested by MHRA added.  
4. Section 3.9.2, QTc Stopping Criteria, page 67; Section 3.10.3, Dose 
Modifications Table 13, page 77.

Rationale: MHRA requested subjects with increase in QTc > 60 msec from 
baseline be withdrawn from study treatment.
5. Section 12.1, Data Dissemination and Communication Plan, page 132.

Rationale: MHRA requested a detailed communication plan be included in the 
protocol.  This plan should address the assignment of subjects to a cohort with 
consideration of cohort size and number of sites, and should address how 
dissemination of safety data to all sites will be handled.


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List of Specific Changes
Regulatory Agency Identifying Number(s):
OLD TEXT
Compound Number
IND Number
EudraCT Number
GSK2857916
119333
2003-004549-18
NEW TEXT
Compound Number
IND Number
EudraCT Number
GSK2857916
119333
20032013-004549-18
Protocol Synopsis, Exclusion Criteria
NEW TEXT
18. Current corneal disease or a history of corneal disease.
Section 3.3 Part 1: Dose-Escalation Phase
NEW TEXT
Note:  For details on data dissemination and communication with sites (dose escalation 
meetings and safety update meetings), refer to Section 12.1.
Section 3.3.1.2.1 Planned Dose Levels, 2nd Paragraph
PREVIOUS TEXT
Description of the New Continual Reassessment Method: After each cohort, a dosing 
recommendation for the next cohort will be made using the N-CRM [Neuenschwander, 
2008].  All available data, including safety, PK and PD data from current and prior 
cohorts will be reviewed at the dose escalation meeting. Although the N-CRM will be 
used to recommend the next dosing level, clinical judgment by the Medical Monitor and 
internal dose-escalation committee in consultation with the investigators can halt 
enrolment into lower dose cohorts as deemed appropriate at any time during the trial.
REVISED TEXT
Description of the New Continual Reassessment Method: After each cohort, a dosing 
recommendation for the next cohort will be made using the N-CRM [Neuenschwander, 
2008].  All available data, including safety, PK and PD data from current and prior 
cohorts will be reviewed at the dose escalation meeting (see Section 12.1). Although the 


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N-CRM will be used to recommend the next dosing level, clinical judgment by the 
Medical Monitor and internal dose-escalation committee in consultation with the 
investigators can halt enrolment into lower dose cohorts as deemed appropriate at any 
time during the trial.
Section 3.3.1.2.1 Planned Dose Levels, 6th Paragraph
PREVIOUS TEXT
The recommended dose will be the dose with the highest posterior probability of lying in 
the target toxicity interval with the additional requirement that the sum of the posterior 
probabilities of the DLT rate lying in the excessive toxicity or unacceptable toxicity 
range is less than 25%.  Selection of the next dose cohort to be enrolled is also subject to 
the constraint that the next dose level can be no more than two times that of the current 
dose level. An updated estimate of the toxicity curve will be provided at the time of each 
dose escalation meeting.
REVISED TEXT
The recommended dose will be the dose with the highest posterior probability of lying in 
the target toxicity interval with the additional requirement that the sum of the posterior 
probabilities of the DLT rate lying in the excessive toxicity or unacceptable toxicity 
range is less than 25%.  Selection of the next dose cohort to be enrolled is also subject to 
the constraint that the next dose level can be no more than two times that of the current 
dose level. An updated estimate of the toxicity curve will be provided at the time of each 
dose escalation meeting (see Section 12.1).
Section 3.3.3, Dose Limiting Toxicity – Part 1 Only
PREVIOUS TEXT
Any subject in Part 1 (Dose Escalation) who received at least one dose of the drug 
(regardless of schedule) will be evaluated for DLTs 
REVISED TEXT
Any subject in Part 1 (Dose Escalation) who received at least one dose of the drug 
(regardless of schedule) will be evaluated for DLTs.  Safety data together with DLTs 
will be reviewed during the dose escalation meetings prior to opening enrollment 
into subsequent cohorts (see Section 12.1).
Section 3.4, RP2 Dose and Administration Schedule Selection for Part 2
NEW TEXT
Note:  For details on data dissemination and communication with sites (safety update 
meetings), refer to Section 12.1.


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Section 3.9.2, QTc Stopping Criteria
PREVIOUS TEXT
If a subject that meets the corrected QT (QTc)1 interval duration criteria below, study 
treatment(s) will be withheld.  

QT interval corrected for heart rate by Fridericia’s formula (QTcF) >530 msec
1Based on average QTc value of triplicate electrocardiograms (ECGs) to include manual 
over-read.  For example, if an ECG demonstrates a prolonged QT interval, obtain 2 
additional ECGs over a brief period (e.g., within approximately 10 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 subjects 
should have study treatment withheld.
If the QTc prolongation resolves to Grade 1 or baseline, the subject may be re-started on 
the study treatment if the investigator and GSK Medical Monitor agree that the subject 
will benefit from further treatment.
REVISED TEXT
Study treatment will be withheld in If a subject that who meets the corrected QT 
(QTc)1 interval duration criteria below, study treatment(s) will be withheld.  

QT interval corrected for heart rate by Fridericia’s formula (QTcF) >530500 msec
or

Increase in QTc of > 60 msec from baseline
1Based on average QTc value of triplicate electrocardiograms (ECGs) to include manual 
over-read.  For example, if an ECG demonstrates a prolonged QT interval, obtain 2 
additional ECGs over a brief period (e.g., within approximately 10 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 subjects 
should have study treatment withheld.
If the QTc prolongation resolves to Grade 1 or baseline, the subject may be re-started on 
the study treatment if the investigator and GSK Medical Monitor agree that the subject 
will benefit from further treatment.


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Section 3.10.3, Dose Modifications
PREVIOUS TEXT
Table 13
Dose Adjustment/Stopping Criteria
Toxicity Gradea
Dose Modification of GSK2857916
Grade 1

Continue at current dose level. Consider supportive care 
recommendations 
Grade 2

If toxicity is considered not clinically relevant, continue with 100% 
scheduled dose

If toxicity is considered clinically relevant withhold the dose until 
toxicity resolves to Grade 1 or baseline. If resolved within 14 days, 
then restart at current dose level. Consider supportive care 
recommendations

If not resolved within 14 days, discuss with GSK Medical Monitor 
Grade 3

Withhold dose until toxicity resolves to Grade 1 or baseline, unless 
condition fits exceptions noted below. If resolved within 14 days, 
resume treatment at dose reduced by 25% (first dose reduction), or 50% 
(second dose reduction). Consider supportive care recommendations.  
If not resolved within 14 days, discuss with GSK Medical Monitor  
Exceptions:

Subjects who develop G3 toxicities which respond to standard treatment 
and resolve to G1 within 48 hours may continue treatment at 
scheduled or reduced dose

Permanently discontinue for grade 3 or greater QTc prolongation ie, 
QTcF >530 msec 

Troponin elevations: See Section 3.9.3 for troponin stopping criteria
Grade 4

Permanently discontinue study medication
Exceptions:

G4 thrombocytopenia with no sign of bleeding, if recovered within 
14 days.  For dose reductions see Section 3.10

G4 lymphopenia (dose reductions by 25-50% may be considered
b.
Considered related to investigational drug.


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REVISED TEXT
Toxicity Gradea
Dose Modification of GSK2857916
Grade 1

Continue at current dose level. Consider supportive care 
recommendations 
Grade 2

If toxicity is considered not clinically relevant, continue with 100% 
scheduled dose

If toxicity is considered clinically relevant withhold the dose until 
toxicity resolves to Grade 1 or baseline. If resolved within 14 days, 
then restart at current dose level. Consider supportive care 
recommendations

If not resolved within 14 days, discuss with GSK Medical Monitor 
Grade 3

Withhold dose until toxicity resolves to Grade 1 or baseline, unless 
condition fits exceptions noted below. If resolved within 14 days, 
resume treatment at dose reduced by 25% (first dose reduction), or 50% 
(second dose reduction). Consider supportive care recommendations.  
If not resolved within 14 days, discuss with GSK Medical Monitor  
Exceptions:

Subjects who develop G3 toxicities which respond to standard treatment 
and resolve to G1 within 48 hours may continue treatment at 
scheduled or reduced dose

Permanently discontinue for grade 3 or greater QTc prolongation ie, 
QTcF > 500 500 msec or QTcF increase by > 60 msec from baseline

Troponin elevations: See Section 3.9.3 for troponin stopping criteria
Grade 4

Permanently discontinue study medication
Exceptions:

G4 thrombocytopenia with no sign of bleeding, if recovered within 
14 days.  For dose reductions see Section 3.10

G4 lymphopenia (dose reductions by 25-50% may be considered
c.
Considered related to investigational drug.
Section 5.2.2, Exclusion Criteria
NEW TEXT
18. Current corneal disease or a history of corneal disease.
Section 12.1, Data Dissemination and Communication Plan
NEW TEXT
The GSK Medical Monitor will review screening packets to ensure that subjects being 
considered for enrollment meet eligibility criteria prior to entering the study.  Subjects 
will not be assigned a study number until their screening packet is reviewed and approved 
by the GSK Medical Monitor.  GSK will remain in constant contact with the clinical sites 
during the enrolment period to ensure that cohort enrolment in Parts 1 and 2 of this study 


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are completed as per protocol.  Investigators will be informed about available openings 
for enrolment on the trial and will be asked to pre-screen their subjects to determine 
potential eligibility, and to avoid over-enrolment. Enrolment will be offered to a given 
site for a limited period of time, and if the site chosen cannot successfully enrol a subject 
within a pre-specified time period then another site will be offered the opportunity to 
enrol a subject.  
During Part 1 of the study, Study Team Safety Update Meetings will be held every three 
weeks to review relevant data with the Principal Investigators (or delegates) and site staff. 
These meetings will be held on an “as needed” basis (but no less frequent than once a 
month) during Part 2 (eg, to share safety experience and to communicate results of 
scheduled futility analyses).  Safety, PK, PD, and clinical outcome data available for all 
subjects at the time of the scheduled Safety Update Meeting will be reviewed and 
summarized. In addition, Dose Escalation Meetings will be scheduled at the conclusion 
of the DLT assessment period for subjects enrolled in each cohort to review safety PK, 
and PD data and determine the next dose level appropriate for study. Dose escalation 
decisions will be made with team and investigator agreement after review of available 
safety data from at least one cycle of therapy with GSK2867916 (ie, 21 days for the once 
every 3 weeks schedule and 28 days for weekly schedule).  All dose escalation or safety 
decisions will be documented in writing with copies maintained at each site and the 
Master Study Files at GSK.  Available data will be provided to participants prior to each 
scheduled Safety or Dose Escalation Meeting.
Attendees of Safety Update and Dose Escalation Meetings will include but not limited to 
all clinical investigators (or designees) and site staff, the GSK Medical Monitor, Clinical 
Investigation Lead, Clinical Operations Study Lead (USA and Local Operating Company 
designees), Data Quality Leader, Global Clinical Safety and Pharmacovigilance 
Representative, Statistician, Pharmacokineticist, and Translational Medicine Lead.


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16.11.2.
Amendment 2
Where the Amendment Applies
Canada, United Kingdom, United States
Summary of Amendment Changes with Rationale
1. Page 1, Subject

Rationale: updated key words of subject
2. Page 2, Amendment 1 Rationale

Rationale:  updated wording of Amendment 1 rationale for clarity
3. Page 12, List of Abbreviations

Rationale:  removed abbreviations no longer being used in the protocol and 
made corrections to typographical errors
4. Page 18, Study Objectives, Endpoints and Hypotheses and Section 2

Rationale:  corrected definition of MR from Minor Response to Minimal 
Response
5. Page 20, Protocol Synopsis Inclusion Criteria and Section 5.2.1 Inclusion Criteria

Rationale:  updated Inclusion Criterion #2 to add minimum weight requirement 
to ensure subjects do not exceed maximum blood volume sampled for research 
tests within a month
6. Page 27, Clinical Activity Assessment

Rationale: corrected definition of MR from Minor Response to Minimal 
Response
7. Section 1.2.3.4.1 and Section 10

Rationale:  added restriction for use of Pgp inhibitors per FDA request
8. Section 3.1, Table 3

Rationale:  added “serial” to add clarity on PK samples required for subjects in 
Dose Escalation

Per FDA request, added text that maxmimum dose to be administered will not 
exceed 5mg/kg
9. Section 3.3.1.1

Rationale:  Per FDA request, removed specification of “clinically significant” 
in reference to toxicities
10. Section 3.1, Section 3.3.1.2.1, and Section 3.8


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
Rationale:  Per FDA request, added the maximum dose of drug to be 
administered in the study
11. Section 3.3.3

Rationale:  Per FDA request, removed specification of “clinically significant” 
in reference to toxicities.  Clarified the DLT definitions of thrombocytopenia 
and skin reactions
12. Section 3.8

Rationale: Per FDA request, added text that maxmimum dose to be 
administered will not exceed 5mg/kg
13. Section 3.9.5

Rationale: Added clarification on use of premedication before the first dose if 
warranted.  Added clarification on management of subjects with grade 3 
allergic reactions or cytokine release syndrome
14. Section 3.9.6

Rationale:  Added further clarification on management of subjects with allergic 
reactions per FDA request
15. Section 3.9.8

Rationale:  Per FDA request, added stopping criteria for subjects with corneal 
toxicity
16. Section 3.10.2

Rationale: Clarifications added on dose adjustments and stopping criteria for 
serum creatinine, thrombocytopenia, INR prolongation, and ocular toxicity.
17. Section 4

Rationale:  Added Lot # restrictions per FDA request. Updated storage 
conditions of prepared drug.
18. Section 6.3

Rationale:  Per FDA request, added clarification on discontinuation from study
19. Section 7.1

Rationale:  Updated all Time and Events tables for Dose Escalation and Dose 
Expansion to add Hepatitis B and C testing at Screening, removal of sBCMA 
and cytokine samples at Screening, and clarification on PD samples
20. Section 7.3.6, Table 15

Rationale:  Updated clinical laboratory test table to remove tests not required in 
the study
21. Section 7.4.1

Rationale:  Updated blood volume for PK samples
22. Appendix 10


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
Rationale:  updated blood volume tables
23. Appendix 11

Rationale:  New appendix added per FDA request to list Pgp Inhibitors
List of Specific Changes
Example heading is listed below, and should be modified as appropriate.
Title Page, Subject
PREVIOUS TEXT
Multiple Myeloma, BCMA expressing, Advanced Hematologic Malignancies
REVISED TEXT
Multiple Myeloma, BCMA expressing, Advanced Hematologic Malignancies
Revision Chronology
PREVIOUS TEXT
2012N155299_01
2014-MAR-01
Amendment 01: Country specific 
Amendment for the United Kingdom to 
address required changes per MHRA.  
Updated Exclusion Criteria to exclude 
subjects with current or medical history 
of corneal pathology.  Updated QTc 
withdrawal criterion to modify QTc 
withdrawal for QTc 500msec and to 
include > 60 msec increase from 
baseline.  Updated Data Management 
Section 12 to include details on 
dissemination of data and 
communication plan.  


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REVISED TEXT
2012N155299_01
2014-MAR-01
Amendment 01: Country specific 
Amendment for the United Kingdom to 
address required changes per MHRA.  
Updated Exclusion Criteria to exclude 
subjects with current or medical corneal 
disease or history of corneal pathology
disease.  Updated QTc withdrawal 
criterion to modify QTc withdrawal for 
QTc 500msec and to include > 60 
msec increase from baseline.  Updated 
Data Management Section 12 to 
include details on dissemination of data 
and communication plan.  
List of Abbreviations
PREVIOUS TEXT
CPK
Creatine Phosphokinase
CK
Creatinine kinase
CK-MB
Creatinine kinase MB-isoenzyme
MR
Minor response
REVISED TEXT
CPK
Creatine Phosphokinase
CK
Creatinine kinase
CK-MB
Creatinine kinase MB-isoenzyme
MR
Minor Minimal response


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Protocol Synopsis, Study Objectives
PREVIOUS TEXT
Secondary

To explore the initial anti-
tumor activity of 
GSK2857916 in subjects 
with relapsed/refractory 
MM and other BCMA 
expressing hematologic 
malignancies

Clinical activity measured as Overall Response 
Rate (ORR) which is defined as follows:
o
For MM: the percentage of subjects 
achieving confirmed partial response or 
better (PR) 
o
In addition, the percentage of subjects with 
minor response (MR) will be assessed for 
clinical benefit rate (CBR) (Appendix 1)
o
For Other Hematologic Malignancies: the 
percentage of subjects achieving PR or 
better (PR) (Appendix 2 and Appendix 3) 
REVISED TEXT
Secondary

To explore the initial anti-
tumor activity of 
GSK2857916 in subjects 
with relapsed/refractory 
MM and other BCMA 
expressing hematologic 
malignancies

Clinical activity measured as Overall Response 
Rate (ORR) which is defined as follows:
o
For MM: the percentage of subjects 
achieving confirmed partial response or 
better (PR) 
o
In addition, the percentage of subjects with 
minor minimal response (MR) will be 
assessed for clinical benefit rate (CBR) 
(Appendix 1)
o
For Other Hematologic Malignancies: the 
percentage of subjects achieving PR or 
better (PR) (Appendix 2 and Appendix 3) 
Protocol Synopsis, Inclusion Criteria
PREVIOUS TEXT 
2. Male or female, 18 years or older (at the time consent is obtained).


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REVISED TEXT
2.
Male or female, 18 years or older (at the time consent is obtained) and must have a 
body weight of at least 45 kg (99 lb).
Protocol Synopsis, Clinical Activity Assessment
PREVIOUS TEXT
CLINICAL ACTIVITY 
ASSESSMENT
Clinical activity will be measured as Overall Response Rate 
(ORR) which is defined as follows:
For MM: the percentage of subjects with confirmed 
stringent complete response (sCR), complete response 
(CR), very good partial response (VGPR), and partial 
response (PR) as assessed by 2011 recommendation of 
the International Myeloma Working Group (IMWG) 
Panel I.   Clinical benefit rate (CBR), including minor 
response (MR), may be considered in addition to ORR.
(Appendix 1).  
For Other Hematologic Malignancies: the percentage of 
subjects with confirmed CR, PR, as described in the 
Revised Response Criteria for Malignant Lymphoma 
(Appendix 2) and for CLL Appendix 3). 
REVISED TEXT
CLINICAL ACTIVITY 
ASSESSMENT
Clinical activity will be measured as Overall Response Rate 
(ORR) which is defined as follows:
For MM: the percentage of subjects with confirmed 
stringent complete response (sCR), complete response 
(CR), very good partial response (VGPR), and partial 
response (PR) as assessed by 2011 recommendation of 
the International Myeloma Working Group (IMWG) 
Panel I.   Clinical benefit rate (CBR), including minor
minimal response (MR), may be considered in addition 
to ORR. (Appendix 1).  
For Other Hematologic Malignancies: the percentage of 
subjects with confirmed CR, PR, as described in the 
Revised Response Criteria for Malignant Lymphoma 
(Appendix 2) and for CLL Appendix 3). 


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Section 1.2.3.4.1, Victim interaction potential
NEW TEXT
Concomitant dosing of GSK2857916 with strong Pgp inhibitors should be avoided unless 
considered medically necessary (See Appendix 11:  Pgp Inhibitors for list of relevant Pgp 
inhibitors).
Section 2, Objective(s), Endpoint(s) and Hypothesis
PREVIOUS TEXT
Secondary
Objective
Endpoint

To explore the initial anti-
tumor activity of 
GSK2857916 in subjects 
with relapsed/refractory 
MM and other BCMA 
expressing hematologic 
malignancies

Clinical activity measured as Overall Response 
Rate (ORR) which is defined as follows:
o
For MM: the percentage of subjects 
achieving confirmed partial response or 
better (PR) 
o
In addition, the percentage of subjects with 
minor response (MR) will be assessed for 
clinical benefit rate (CBR) (Appendix 1)
o
For Other Hematologic Malignancies: the 
percentage of subjects achieving PR or 
better (PR) (Appendix 2 and Appendix 3) 
REVISED TEXT
Secondary
Objective
Endpoint

To explore the initial anti-
tumor activity of 
GSK2857916 in subjects 
with relapsed/refractory 
MM and other BCMA 
expressing hematologic 
malignancies

Clinical activity measured as Overall Response 
Rate (ORR) which is defined as follows:
o
For MM: the percentage of subjects 
achieving confirmed partial response or 
better (PR) 
o
In addition, the percentage of subjects with 
minor minimal response (MR) will be 
assessed for clinical benefit rate (CBR) 
(Appendix 1)
o
For Other Hematologic Malignancies: the 
percentage of subjects achieving PR or 
better (PR) (Appendix 2 and Appendix 3) 


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Section 3.1, Discussion of Study Design, Table 3 Study Design
PREVIOUS TEXT
Part 1 Dose Escalation (n=up to 30 subjects)
Population:  relapsed/refractory MM
Characterize safety, PK, PD, immunogenicity and establish RP2 dose of GSK2857916
Schedule 1: GSK2587916 once every 3 weeks (21-day cycle) (n=~20)
Schedule 2: GSK2587916 once weekly for 3 consecutive weeks, 1-week rest (28-day cycle) 
(n=~9)
PK samples will be collected from all subjects in Part 1
REVISED TEXT
Part 1 Dose Escalation (n=up to 30 subjects)
Population:  relapsed/refractory MM
Characterize safety, PK, PD, immunogenicity and establish RP2 dose of GSK2857916
Schedule 1: GSK2587916 once every 3 weeks (21-day cycle) (n=~20)
Schedule 2: GSK2587916 once weekly for 3 consecutive weeks, 1-week rest (28-day cycle) 
(n=~9)
Serial PK samples will be collected from all subjects in Part 1
Section 3.1, Discussion of Study Design
PREVIOUS TEXT
This is a First Time in Human (FTIH), open-label, dose escalation trial consisting of two 
parts: a Part 1 dose escalation phase and a Part 2 expansion phase for safety, and clinical 
activity testing (Table 3 and Section 3.2). The study will enroll a total of approximately 
80 subjects with relapsed/refractory MM or other BCMA-expressing hematologic 
malignancies.  
REVISED TEXT
This is a First Time in Human (FTIH), open-label, dose escalation trial consisting of two 
parts: a Part 1 dose escalation phase and a Part 2 expansion phase for safety, and clinical 
activity testing (Table 3 and Section 3.2). The study will enroll a total of approximately 


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80 subjects with relapsed/refractory MM or other BCMA-expressing hematologic 
malignancies.  The maximum dose to be administered in this trial will not exceed 5 
mg/kg.
Section 3.3.1.1, Single Subject Cohort Run-in (Schedule 1 only)
PREVIOUS TEXT

A single subject will be enrolled at each dose level as outlined in Table 4 until 
occurrence of a clinically significant ≥ Grade 2 toxicity for which relationship to 
the investigational agent cannot be ruled out.

Initially, GSK2857916 will be administered (IV) via 60 min infusion once every 
three weeks (21 days = 1 cycle) on Schedule 1. One subject or the sentinel 
subject ie, the very first subject on the study; will initially be enrolled at the 
starting dose of 0.03 mg/kg in Cohort 1 (Refer to Section 3.6.4 for starting dose 
rationale). The initial dose will be given to the sentinel subject.  Serial blood 
samples will be collected for PK.  The sentinel subject must remain under 
observation for at least 24 hours after dosing before discharge.  GSK2857916 
(intact and total [intact + unconjugated antibody]) and cys-mcMMAF plasma 
concentrations will be analyzed and reviewed together with the safety data (DLT 
period). If the first dose is considered tolerated, the sentinel subject will be 
allowed to stay on the study and receive subsequent doses at the same dose level 
(ie, 0.03 mg/kg) as scheduled, every three weeks (21 days interval) for up to 16 
doses (or until disease progression, toxicity or withdrawal of consent). 

If the sentinel subject does not experience a ≥ clinically significant Grade 2 
toxicity for which relationship to the investigational agent cannot be ruled out
during the first cycle (within 21 days), the next subject will be allowed to enroll 
in the next cohort at a dose increased by ≤100% of the starting dose.  Dose 
escalation with increments up to 100% of the previous dose will continue with 
enrolment of 1 subject per cohort until the occurrence of the first clinically 
significant ≥ Grade 2 toxicity for which relationship to the investigational agent 
cannot be ruled out. (run in procedure outlined  in Table 4)

The single subject (small cohort) run-in will be halted when the first clinically 
significant ≥ Grade 2 toxicity for which relationship to the investigational agent 
cannot be ruled out occurs in one subject in Cycle 1 (21 days).  At this point, the 
cohort will be expanded to 3 or more subjects at the same dose level and the 
escalation will continue to follow the N-CRM procedure as outlined in Table 4


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Table 19
Single Subject (Small Cohort) Run-In Procedure for GSK2857916 given 
on Schedule 1 (once every 21 days)
Dose Level 
Number of subjects 
with ≥G2 toxicity
Dose Escalation/Action
Dose Level 1/Cohort 1
0 out of 1 subject
(Sentinel subject)
Predicted starting dose 0.03 mg/kg every 21 
days
Dose Level 2/Cohort 2
0 out of 1 subject
Escalate to the next dose level with increase   
≤100%  of the starting dose
Dose Level 3 and 
beyond/Cohort 3 and 
beyond
0 out of 1 subject
Escalate to the next dose level with increase of 
≤100% of the dose tested in the previous cohort 
1 out of 1 subject*
Switch to Cohort size of 3 or more subjects 
*Increase of doses up to 100% of the previous dose may continue until the first clinically 
significant ≥Grade 2 toxicity for which relationship to the investigational agent cannot be 
ruled out occurs in one subject in Cycle 1 (21 days).  At this point the single subject (small 
cohort) run-in is halted.  Continue with N-CRM, with cohort sizes of 3 or more subjects.  Increase 
of doses 100% will be considered for subsequent cohorts of 3 or more subjects. 
REVISED TEXT

A single subject will be enrolled at each dose level as outlined in Table 4 until 
occurrence of a clinically significant ≥ Grade 2 toxicity for which relationship to 
the investigational agent cannot be ruled out.

Initially, GSK2857916 will be administered (IV) via 60 min infusion once every 
three weeks (21 days = 1 cycle) on Schedule 1. One subject or the sentinel 
subject ie, the very first subject on the study; will initially be enrolled at the 
starting dose of 0.03 mg/kg in Cohort 1 (Refer to Section 3.6.4 for starting dose 
rationale).  The initial dose will be given to the sentinel subject.  Serial blood 
samples will be collected for PK.  The sentinel subject must remain under 
observation for at least 24 hours after dosing before discharge.  GSK2857916 
(intact and total [intact + unconjugated antibody]) and cys-mcMMAF plasma 
concentrations will be analyzed and reviewed together with the safety data (DLT 
period). If the first dose is considered tolerated, the sentinel subject will be 
allowed to stay on the study and receive subsequent doses at the same dose level 
(ie, 0.03 mg/kg) as scheduled, every three weeks (21 days interval) for up to 16 
doses (or until disease progression, toxicity or withdrawal of consent). 

If the sentinel subject does not experience a ≥ clinically significant Grade 2 
toxicity for which relationship to the investigational agent cannot be ruled out
during the first cycle (within 21 days), the next subject will be allowed to enroll 
in the next cohort at a dose increased by ≤100% of the starting dose.  Dose 
escalation with increments up to 100% of the previous dose will continue with 
enrolment of 1 subject per cohort until the occurrence of the first clinically 
significant ≥ Grade 2 toxicity for which relationship to the investigational agent 
cannot be ruled out. (run in procedure outlined  in Table 4)


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
The single subject (small cohort) run-in will be halted when the first clinically 
significant ≥ Grade 2 toxicity for which relationship to the investigational agent 
cannot be ruled out occurs in one subject in Cycle 1 (21 days).  At this point, the 
cohort will be expanded to 3 or more subjects at the same dose level and the 
escalation will continue to follow the N-CRM procedure as outlined in Table 4
Table 20
Single Subject (Small Cohort) Run-In Procedure for GSK2857916 given 
on Schedule 1 (once every 21 days)
Dose Level 
Number of subjects 
with ≥G2 toxicity
Dose Escalation/Action
Dose Level 1/Cohort 1
0 out of 1 subject
(Sentinel subject)
Predicted starting dose 0.03 mg/kg every 21 
days
Dose Level 2/Cohort 2
0 out of 1 subject
Escalate to the next dose level with increase   
≤100%  of the starting dose
Dose Level 3 and 
beyond/Cohort 3 and 
beyond
0 out of 1 subject
Escalate to the next dose level with increase of 
≤100% of the dose tested in the previous cohort 
1 out of 1 subject*
Switch to Cohort size of 3 or more subjects 
*Increase of doses up to 100% of the previous dose may continue until the first clinically 
significant ≥Grade 2 toxicity for which relationship to the investigational agent cannot be 
ruled out occurs in one subject in Cycle 1 (21 days).  At this point the single subject (small 
cohort) run-in is halted.  Continue with N-CRM, with cohort sizes of 3 or more subjects.  Increase 
of doses 100% will be considered for subsequent cohorts of 3 or more subjects. 
Section 3.3.1.2.1, Planned Dose Levels
NEW TEXT
Prior to the start of the study, projected dose levels on Schedule 1 (in mg/kg) are 0.03, 
0.06, 0.12, 0.24, 0.48, 0.96, 1.92, 2.88, 3.6, and 4.5 mg/kg.  Additional doses and 
schedules may be explored based on emerging safety, PK, and PD data. The maximum 
dose to be administered in this trial will not exceed 5 mg/kg.
Section 3.3.3, Dose Limiting Toxicity – Part 1 only
PREVIOUS TEXT
Subjects who have been withdrawn from the study for reasons other than toxicity but 
prior to completion of DLT observation period will be replaced.An event will be 
considered a DLT if it is clinically significant and its relationship to the investigational 
agent cannot be ruled out occurs within the DLT reporting period (first 21 days of 
treatment for schedule 1, and first 28 days for schedule 2) and meets one of the following 
criteria:


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
Albuminuria ≥2000 mg/24 hr which has been confirmed by repeat test at least 7 
days apart and is not considered to be related to disease progression based on 
consultation of investigator with GSK medical monitor

Grade 4 neutropenia (without fever) lasting 7 days 

Febrile neutropenia lasting 72 hours 

Grade 3 thrombocytopenia associated  with clinically significant bleeding or
Grade 4 thrombocytopenia lasting >7 days and not responding to platelet 
transfusions 

Any Grade 3 or greater non-hematologic toxicity as described in Common 
National Cancer Institute-Terminology Criteria for Adverse Events (NCI-
CTCAE) version 4.0 [NCI, 2009]  with the exception of the following Grade 3 
events that can be controlled within 48 hours with routine supportive measures
o
Nausea and vomiting that can be controlled with anti-emetics
o
Diarrhea that can be controlled with anti-diarrheals
o
Rash or allergic reactions that can be controlled with antihistamines and 
steroids
o
Clinically asymptomatic electrolyte abnormalities which can be corrected 
within 48 hours)

Liver toxicity meeting pre-specified GSK liver stopping criteria (see Liver in 
Section 3.9.1)
Tumor lysis syndrome does NOT constitute a DLT (Section 3.9.7).
REVISED TEXT
Subjects who have been withdrawn from the study for reasons other than toxicity but 
prior to completion of DLT observation period will be replaced.An event will be 
considered a DLT if it is clinically significant and its relationship to the investigational 
agent cannot be ruled out occurs within the DLT reporting period (first 21 days of 
treatment for schedule 1, and first 28 days for schedule 2) and meets one of the following 
criteria:

Albuminuria ≥2000 mg/24 hr which has been confirmed by repeat test at least 7 
days apart and is not considered to be related to disease progression based on 
consultation of investigator with GSK medical monitor

Grade 4 neutropenia (without fever) lasting 7 days 

Febrile neutropenia lasting 72 hours 

Grade 3 thrombocytopenia associated  with clinically significant bleeding or
where estimated blood loss is > 10mL or Grade 4 thrombocytopenia lasting >7 
days and not responding to platelet transfusions 

Any Grade 3 or greater non-hematologic toxicity as described in Common 
National Cancer Institute-Terminology Criteria for Adverse Events (NCI-


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CTCAE) version 4.0 [NCI, 2009]  with the exception of the following Grade 3 
events that can be controlled within 48 hours with routine supportive measures
o
Nausea and vomiting that can be controlled with anti-emetics
o
Diarrhea that can be controlled with anti-diarrheals
o
Rash or allergic other skin reactions that can be controlled with 
antihistamines and steroids
o
Clinically asymptomatic electrolyte abnormalities which can be corrected 
within 48 hours)

Liver toxicity meeting pre-specified GSK liver stopping criteria (see Liver in 
Section 3.9.1)
Tumor lysis syndrome does NOT constitute a DLT (Section 3.9.7).
A subject who develops a DLT will be allowed to stay on study only if the toxicity did 
not meet stopping criteria and recovered to Grade 1 within 14 days, or after a longer 
recovery time if benefit to subject can be demonstrated and if the investigator and 
medical monitor agree that for a given subject the benefits may outweigh the risks.
Section 3.8, Dosage and Administration of Study Treatment(s)
NEW TEXT
The maximum dose to be administered to subjects in this trial is 5 mg/kg.
Section 3.9.5, Infusion-related Reactions and Cytokine Release Syndrome
PREVIOUS TEXT
Premedication is not allowed prior to first infusion. Premedication should be considered 
in any subject who experienced an infusion related reaction at first or any subsequent 
infusion with GSK2857916.
REVISED TEXT
Premedication is not allowed prior to first infusion unless deemed medically appropriate 
by the GSK Medical Monitor in consultation with investigators following evaluation of 
infusion related reactions across cohorts. Premedication should be considered in any 
subject who experienced an infusion related reaction at first or any subsequent infusion 
with GSK2857916.
Section 3.9.6, Allergic and Anaphylactic reaction
PREVIOUS TEXT
As GSK2857916 is a fully humanized ADC, it is considered unlikely for acute allergic 
reactions to occur in response to GSK2857916 exposure; however, all subjects will be 
monitored carefully for evidence of allergic response. A subject that exhibits signs or 
symptoms of severe hypersensitivity or anaphylaxis will receive appropriate medical 


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treatment and remain on study at the discretion of the investigator and after discussion 
with the GSK medical monitor. 
o Further treatment with GSK2857916 needs to be discussed with MM prior 
to next dose administration.
REVISED TEXT
As GSK2857916 is a fully humanized ADC, it is considered unlikely for acute allergic 
reactions to occur in response to GSK2857916 exposure; however, all subjects will be 
monitored carefully for evidence of allergic response. A subject that exhibits signs or 
symptoms of severe hypersensitivity or anaphylaxis will receive appropriate medical 
treatment and remain on study at the discretion of the investigator and after discussion 
with the GSK medical monitor. be withdrawn from the study.
o
Subjects who experience Grade 3 allergic reaction will be withdrawn 
from study 
o Further treatment with GSK2857916 in subjects who experience a Grade 
3 infusion related reaction needs to be discussed with MM prior to next 
dose administration. Those subjects will be allowed to continue on study 
after recovery of the reaction to Grade 1 but will have to receive pre-
medication prior to each subsequent dose of GSK2857916, and their 
infusion time will be extended to 2-4 hours (depending on severity of the 
reaction).
Section 3.9.8, Ocular Toxicity
NEW TEXT
Section 3.9.8, Ocular Toxicity and Stopping Criteria
All subjects will be advised to use prednisolone phosphate 1% or dexamethasone 0.1% 
eye drop 4 times a day (QID) for 4 days starting 1 day prior to each dose. Additional use 
of lubrication eye drops (artificial tears) QID PRN throughout the trial is recommended, 
especially if subject develops any ocular symptoms. Subjects who develop Grade 3 
ocular or corneal toxicity will be permanently removed from study.


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Section 3.10.2, Predicted Toxicities and Proposed Dose 
Adjustments/Stopping Criteria
PREVIOUS TEXT
Thrombocytopenia
Grade 3: >25 and 
<50x109/L

With clinically significant bleeding:  Withhold 
the: 

No clinically significant bleeding: continue 
treatment with  25% dose reduction 
Ocular/corneal 
toxicity
Grade 2/Grade 3

First occurrence:
o
Interrupt treatment with 
GSK2857916
o
Consult ophthalmologist immediately
o
When recovered to G1 Re-start 
treatment with GSK2857916 at 25%  
dose reduction upon resolution to 
G1 

Second occurrence:
o
Interrupt treatment with 
GSK2857916
o
Consult ophthalmologist immediately
o
Once resolved toG1 or less: Restart 
treatment with GSK2857916 at 
additional 25% dose reduction

Third occurrence:

Permanently discontinue treatment with 
GSK2857916 and withdraw subject from study
Grade 4

Consult ophthalmologist immediately

Permanently discontinue treatment with 
GSK2857916
REVISED TEXT
Thrombocytopenia
Grade 3: >25 and 
<50x109/L

With clinically significant bleeding Where 
estimated blood loss is 10 mL: withhold the
treatment:

No clinically significant bleeding: continue 
treatment with  25% dose reduction 
Ocular/corneal 
toxicity
Grade 2/Grade 3

First occurrence:
o
Interrupt treatment with 
GSK2857916
o
Consult ophthalmologist immediately
o
When recovered to G1 Re-start 
treatment with GSK2857916 at 25%  
dose reduction upon resolution to 
G1 

Second occurrence:


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o
Interrupt treatment with 
GSK2857916
o
Consult ophthalmologist immediately
o
Once resolved toG1 or less: Restart 
treatment with GSK2857916 at 
additional 25% dose reduction

Third occurrence:

Permanently discontinue treatment with 
GSK2857916 and withdraw subject from study
Grade 3/Grade 4

Consult ophthalmologist immediately

Permanently discontinue treatment with 
GSK2857916
NEW TEXT
Serum 
creatinine
Grade 3
>3.0mg/dL from
baseline
or
3.0-6.0xULN

Provide appropriate medical treatment. 

Withdraw permanently from trial
INR prolongation
>2.5

Evaluate and provide medical treatment if 
necessary

If INR prolongation is not related to use of 
anticoagulants withdraw subject from study
Section 3.10.3,   Dose Modifications, Table 13 Dose Adjustment/Stopping 
Criteria
PREVIOUS TEXT
Toxicity Gradea
Dose Modification of GSK2857916
Grade 3

Withhold dose until toxicity resolves to Grade 1 or baseline, unless 
condition fits exceptions noted below. If resolved within 14 days, 
resume treatment at dose reduced by 25% (first dose reduction), or 50% 
(second dose reduction). Consider supportive care recommendations.  
If not resolved within 14 days, discuss with Medical Monitor.  
Exceptions:

Subjects who develop G3 toxicities which respond to standard treatment 
and resolve to G1 within 48 hours may continue treatment at 
scheduled or reduced dose

Permanently discontinue for grade 3 or greater QTc prolongation ie, 
QTcF >500 msec or QTcF increase by > 60 msec from baseline

Troponin elevations: See Section 3.9.3 for troponin stopping criteria
aConsidered related to investigational drug.


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REVISED TEXT
Toxicity Gradea
Dose Modification of GSK2857916
Grade 3

Withhold dose until toxicity resolves to Grade 1 or baseline, unless 
condition fits exceptions noted below. If resolved within 14 days, 
resume treatment at dose reduced by 25% (first dose reduction), or 50% 
(second dose reduction). Consider supportive care recommendations.  
If not toxicity is resolved within period longer than 14 days, discuss 
with Medical Monitor. continuation of treatment may be considered on 
an individual basis if benefit to subject can be demonstrated and if 
the investigator and medical monitor agree that for a given subject 
the benefits may outweigh the risks  
Exceptions:

Subjects who develop G3 toxicities which respond to standard treatment 
and resolve to G1 within 48 hours may continue treatment at 
scheduled or reduced dose

Permanently discontinue for grade 3 or greater QTc prolongation ie, 
QTcF >500 msec or QTcF increase by > 60 msec from baseline

Troponin elevations: See Section 3.9.3 for troponin stopping criteria
aConsidered Possibly related to investigational drug.
Section 4.1, Description of Investigational Product
NEW TEXT
Lot number
132373860
GSK2857916 will be provided to sites by GSK.  The contents of the label will be in 
accordance with all applicable regulatory requirements. Only Lot#132373860 of drug 
product will be used for this trial.
Section 4.2, Preparation/Handling/Storage of GSK2857916 Investigational 
Product
PREVIOUS TEXT
Preparation
GSK2857916 Solution for Infusion, 20 mg/mL is supplied as a frozen liquid.  Before use, 
thaw each vial of GSK2857916 for Infusion, 20mg/mL, 1.5mL for up to 4 hours under 
refrigerated conditions, protected from light.  Following thawing, gently swirl the vial to 
ensure uniformity.  GSK2857916 should be diluted in normal saline (0.9%) to no more 
than 2 mg/mL and no less than 0.2 mg/mL.


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The dosing solution of GSK2857916 can be held up to 8 hours at room temperature 
(diluted drug product in bag) from a stability perspective, but should be used as soon as 
possible as the product does not contain an antimicrobial preservative.
Administration
GSK2857916 is compatible with polyvinylchloride-lined or polyolefin-lined intravenous 
infusion administration sets, 0.2 micron polyethersulfone filters, or optionally a 
polyurethane catheter.  Doses of GSK2857916 are to be administered as an IV infusion 
via an infusion pump that can ensure precision to the decimal point of a mL for the 
infusion rate at lower doses. It is recommended to prime the IV tubing with at least 15 
mL prior to dosing.
Storage
GSK2857916 must be stored in a secure area under the appropriate physical conditions 
for the product.  Access to and administration of the GSK2857916 will be limited to the 
investigator and authorized site staff.  GSK2857916 must be dispensed or administered 
only to subjects enrolled in the study and in accordance with the protocol.  
GSK2857916 is to be stored at a temperature range of -50C to -15C.  Maintenance of a 
temperature log is required. 
The expiry date, where required, is stated on the product label.
REVISED TEXT
Preparation
GSK2857916 Solution for Infusion, 20 mg/mL is supplied as a frozen liquid (Lot# 
132373860).  Before use, thaw each vial of GSK2857916 for Infusion, 20mg/mL, 1.5mL 
for up to 4 hours under refrigerated conditions, protected from light.  Following thawing, 
gently swirl the vial to ensure uniformity.  GSK2857916 should be diluted in normal 
saline (0.9%) to no more than 2 mg/mL and no less than 0.2 mg/mL.
The dosing solution of GSK2857916 can be held up to 24 hours under refrigerated 
conditions or 4 8 hours at room temperature (diluted drug product in bag) from a stability 
perspective, but should be used as soon as possible as the product does not contain an 
antimicrobial preservative.
Administration
GSK2857916 is compatible with polyvinylchloride-lined or polyolefin-lined intravenous 
infusion administration sets, 0.2 micron polyethersulfone filters, or optionally a 
polyurethane catheter.  Doses of GSK2857916 are to be administered as an IV infusion 
via an infusion pump that can ensure precision to the decimal point of a mL for the 
infusion rate at lower doses. It is recommended to prime the IV tubing with at least 15 
mL prior to dosing.


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Administration of drug product in this trial is restricted to Lot#132373869.
Storage
GSK2857916 must be stored in a secure area under the appropriate physical conditions 
for the product.  Access to and administration of the GSK2857916 will be limited to the 
investigator and authorized site staff.  GSK2857916 must be dispensed or administered 
only to subjects enrolled in the study and in accordance with the protocol.  
GSK2857916 is to be stored at a temperature range of -50C to -15C.  Maintenance of a 
temperature log is required. 
The expiry date, where required, is stated on the product label. Only Lot#132373860 of 
drug product is acceptable for use in this trial.
Section 5.2.1, Inclusion Criteria
PREVIOUS TEXT
2.
Male or female, 18 years or older (at the time consent is obtained).
REVISED TEXT
2. Male or female, 18 years or older (at the time consent is obtained) and must have a 
body weight of at least 45 kg (99 lb). 
Section 6.3, Permanent Discontinuation fro Study Treatment
PREVIOUS TEXT

a dose delay of >14 days unless the investigator or GSK Medical Monitor agree 
that further treatment may benefit the subject. Exceptions apply to 
nephrotoxicity as outlined in Section 3.10.2
REVISED TEXT

a dose delay of >14 days unless the investigator or GSK Medical Monitor agree 
that subject derives benefit and that further treatment benefits will outweigh the 
risks may benefit the subject.   Exceptions apply to nephrotoxicity as outlined in 
Section 3.10.2


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Section 7.1.1.1, Every 3 Weeks Dosing Schedule for Multiple Myeloma
PREVIOUS TEXT
Study 
Assessments1
Screen2
DAY 
1 C1
DAY 
2 C1
DAY 
8 
C1
DAY 
15 
C1
DAY 
1 C2
D1 of C3-C16
END 
OF 
STUDY
3-MONTH 
OFF-
STUDY 
FOLLOW-
UP
BCMA 
assessment 
(flow) 
X15
Study 
Assessments1
Screen2
DAY 
1 C1
Day 
2 
C1
Day 
8 
C1
DAY 
15 
C1
DAY 
1 C2
D1 of C3-C16
END 
OF 
STUDY
3-MONTH 
OFF-
STUDY 
FOLLOW-
UP
PD 
X
X
Serum (soluble BCMA)
X18
X18
X18
X18
X18
X18
Predose at the start 
of each cycle
X18
Serum 
(cytokines/chemokines)
X19
X19
X
X19
At predose and EOI 
on D1 of each cycle
X
15. Sample(s) collected for analysis by central lab.   
18. A single sample for sBCMA will be collected at screening, C1D8, C1D15 and at the End of Study visit. 
sBCMA samples will also be collected on  C1D1 at EOI (5 minutes) and on C1D2 24h post SOI.  On C2D1 
sBCMA will be collected pre-dose (within 30 minutes prior to SOI) and at the EOI (5 minutes)
REVISED TEXT
Study 
Assessments1
Screen2
DAY 
1 C1
DAY 
2 C1
DAY 
8 
C1
DAY 
15 
C1
DAY 
1 C2
D1 of C3-C16
END 
OF 
STUDY
3-MONTH 
OFF-
STUDY 
FOLLOW-
UP
BCMA 
assessment 
and PD (flow) 
X15
X15


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Study 
Assessments1
Screen2
DAY 
1 C1
Day 
2 
C1
Day 
8 
C1
DAY 
15 
C1
DAY 
1 C2
D1 of C3-C16
END 
OF 
STUDY
3-MONTH 
OFF-
STUDY 
FOLLOW-
UP
PD 
X15
X
Serum (soluble BCMA)
X18
X18
X18
X18
X18
X18
Predose at the start 
of each cycle
X18
Serum 
(cytokines/chemokines)
X19
X19
X
X19
At predose and EOI 
on D1 of each cycle
X
15. Sample(s) collected for analysis by central lab.  The same sample will be used for BCMA (flow) and PD 
during Screening. 
18. A single sample for sBCMA will be collected at screening, C1D8, C1D15 and at the End of Study visit. 
sBCMA samples will also be collected on  C1D1 at predose (within 30 minutes prior to SOI), at EOI (5 
minutes) and on C1D2 24h post SOI.  On C2D1 sBCMA will be collected pre-dose (within 30 minutes prior to 
SOI) and at the EOI (5 minutes)
NEW TEXT
Study 
Assessments1
Screen2
Day 
1 
C1
Day 
2 
C1
Day 
8 
C1
Day 
15 
C1
Day 
1 
C2
D1 of C3-C16
End of 
Study
3-
Month 
Off-
study 
Follow-
up
HBV/HCV tests
X
Section 7.1.1.2,  Weekly Dosing Schedule (Dose Escalation) for Multiple 
Myeloma
PREVIOUS TEXT
Study 
Assessments1
Screen2
DAY 
1 C1
DAY 
2 C1
DAY 
8 
C1
DAY 
15 
C1
DAY 
1 C2
D1 of C3-C16
END 
OF 
STUDY
3-MONTH 
OFF-
STUDY 
FOLLOW-
UP
BCMA 
assessment 
(flow) 
X15


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Study 
Assessments1
Screen2
DAY 
1 C1
DAY 
2 C1
DAY 
8 
C1
DAY 
15 
C1
DAY 
1 C2
D1 of C3-C16
END 
OF 
STUDY
3-MONTH 
OFF-
STUDY 
FOLLOW-
UP
PD
X
X17
Serum (soluble BCMA)
X19
X19
X19
X19
X19
X19
Predose at the 
start of each cycle
X
Serum 
(cytokines/chemokines)
X20
X20
X
X20
X20
X20
At predose and 
EOI on D1 of 
each cycle
X
15. Sample(s) collected for analysis by central lab.
19. A single sample for sBCMA will be collected at screening and on C1D8 predose, and at the End of Study visit. 
sBCMA samples will also  be collected on C1D1 at EOI (5 minutes) and on C1D2 24h post SOI. On C1D15 and 
C2D1 collect at predose (within 30 minutes prior to SOI) and EOI (5 minutes)
REVISED TEXT
Study 
Assessments1
Screen2
DAY 
1 C1
DAY 
2 C1
DAY 
8 
C1
DAY 
15 
C1
DAY 
1 C2
D1 of C3-C16
END 
OF 
STUDY
3-MONTH 
OFF-
STUDY 
FOLLOW-
UP
BCMA 
assessment 
and PD (flow) 
X15
X15, 
17
Study 
Assessments1
Screen2
DAY 
1 C1
DAY 
2 C1
DAY 
8 
C1
DAY 
15 
C1
DAY 
1 C2
D1 of C3-C16
END 
OF 
STUDY
3-MONTH 
OFF-
STUDY 
FOLLOW-
UP
PD
X15
X17
Serum (soluble BCMA)
X19
X19
X19
X19
X19
X19
Predose at the 
start of each cycle
X
Serum 
(cytokines/chemokines)
X20
X20
X
X20
X20
X20
At predose and 
EOI on D1 of 
each cycle
X
15. Sample(s) collected for analysis by central lab. The same sample will be used for BCMA (flow) and PD during 
Screening.
19. A single sample for sBCMA will be collected at screening and on C1D8 predose, and at the End of Study visit. 
sBCMA samples will also  be collected on C1D1 at predose (within 30 minutes prior to SOI), at EOI (5 minutes) 
and on C1D2 24h post SOI. On C1D15 and C2D1 collect at predose (within 30 minutes prior to SOI) and EOI (5 
minutes)


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NEW TEXT
Study 
Assessments1
Screen2
Day 
1 
C1
Day 
2 
C1
Day 
8 
C1
Day 
15 
C1
Day 
1 
C2
D1 of C3-C16
End of 
Study
3-
Month 
Off-
study 
Follow-
up
HBV/HCV tests
X
Section 7.1.2.1, Every 3 Weeks Dosing Schedule for Multiple Myeloma
PREVIOUS TEXT
Study 
Assessments1
Screen2
DAY 
1 
C1
DAY 
8 
C1
DAY 
15 
C1
DAY 1 C2
D1 of C3-C16
END 
OF 
STUDY
3-MONTH 
OFF-
STUDY 
FOLLOW-
UP
BCMA 
assessment 
(flow)
X16
Study 
Assessments1
Screen2
DAY 
1 C1
DAY 
8 
C1
DAY 
15 
C1
DAY 1 C2
D1 of C3-C16
END 
OF 
STUDY
3-MONTH 
OFF-
STUDY 
FOLLOW-
UP
PD
X
X18
Serum (soluble BCMA)
X20
X20
X20
Predose at the 
start of each cycle
X
Serum 
(cytokines/chemokines)
X21
X21
X21
Predose and EOI 
on D1 of each 
cycle
X
16. Sample(s) collected for analysis at central lab. 
20. Collect sBCMA at screening (single sample), C1D1 at EOI (5 minutes), C2D1 at predose (within 30 minutes prior 
to SOI) and at EOI (+- 5 minutes).


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REVISED TEXT
Study 
Assessments1
Screen2
DAY 
1 
C1
DAY 
8 
C1
DAY 
15 
C1
DAY 1 C2
D1 of C3-C16
END 
OF 
STUDY
3-MONTH 
OFF-
STUDY 
FOLLOW-
UP
BCMA 
assessment 
and PD (flow)
X16
X16, 
18
Study 
Assessments1
Screen2
DAY 
1 C1
DAY 
8 
C1
DAY 
15 
C1
DAY 1 C2
D1 of C3-C16
END 
OF 
STUDY
3-MONTH 
OFF-
STUDY 
FOLLOW-
UP
PD
X16
X18
Serum (soluble BCMA)
X20
X20
X20
Predose at the 
start of each cycle
X
Serum 
(cytokines/chemokines)
X21
X21
X21
Predose and EOI 
on D1 of each 
cycle
X
16. Sample(s) collected for analysis at central lab. The same sample will be used for BCMA (flow) and PD during 
Screening. On D8 only postdose PD assessment will be performed, if applicable (refer to footnote 18).
20. Collect sBCMA at screening (single sample), C1D1 predose (within 30 minutes prior to SOI) and at EOI (5 
minutes), C2D1 at predose (within 30 minutes prior to SOI) and at EOI (+- 5 minutes).
NEW TEXT
Study 
Assessments1
Screen2
Day 
1 
C1
Day 
8 
C1
Day 
15 
C1
Day 1 C2
D1 of C3-C16
End 
of 
Study
3-
Month 
Off-
study
Follow-
up
HBV/HCV 
tests
X


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Section 7.1.2.2,  Dose Expansion Weekly Dosing Schedule for Multiple 
Myeloma
PREVIOUS TEXT
Study 
Assessments1
Screen2
DAY 
1 C1
DAY 
8 C1
DAY 
15 
C1
DAY 
1 C2
Day 
15 
C2
D1 of C3-C16
END 
OF 
STUDY
3-MONTH 
OFF-
STUDY 
FOLLOW-
UP
BCMA 
assessment 
and PD (flow)
X15
Study 
Assessments1
Screen2
DAY 
1 C1
Day 
8 
C1
DAY 
15 
C1
DAY 
1 C2
Day 
15 
C2
D1 of C3-C16
END 
OF 
STUDY
3-MONTH 
OFF-
STUDY 
FOLLOW-
UP
PD 
X
X17
Serum (soluble BCMA) 
X19
X19
X19
X19
X19
Predose at the start 
of each cycle
X
Serum 
(cytokines/chemokines)
X20
X20
X20
X20
X20
Predose and EOI on 
D1 of each cycle
X
15. Sample(s) collected for analysis at central lab. The same sample will be used for BCMA (flow) and PD during 
Screening.
19. A single sBCMA sample will be collected at Screening or predose (within 30 minutes prior to SOI) unless 
otherwise specified.  On C1D15 and C2D1 collect samples at predose (within 30 minutes prior to SOI) and at EOI 
(5 minutes).  
REVISED TEXT
Study 
Assessments1
Screen2
DAY 
1 C1
DAY 
8 
C1
DAY 
15 
C1
DAY 
1 C2
Day 
15 
C2
D1 of C3-C16
END 
OF 
STUDY
3-MONTH 
OFF-
STUDY 
FOLLOW-
UP
BCMA 
assessment 
and PD (flow)
X15
X15, 
17


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Study 
Assessments1
Screen2
DAY 
1 C1
Day 
8 
C1
DAY 
15 
C1
DAY 
1 C2
Day 
15 
C2
D1 of C3-C16
END 
OF 
STUDY
3-MONTH
OFF-
STUDY 
FOLLOW-
UP
PD 
X15
X17
Serum (soluble BCMA) 
X19
X19
X19
X19
X19
Predose at the start 
of each cycle
X
Serum 
(cytokines/chemokines)
X20
X20
X20
X20
X20
Predose and EOI on 
D1 of each cycle
X
15. Sample(s) collected for analysis at central lab. The same sample will be used for BCMA (flow) and PD during 
Screening. On D8 only postdose PD assessment will be performed, if applicable (refer to footnote 17).
19. A single sBCMA sample will be collected at Screening or C1D1 predose (within 30 minutes prior to SOI) unless 
otherwise specified.  On C1D15 and C2D1 collect samples at predose (within 30 minutes prior to SOI) and at EOI 
(5 minutes).  
NEW TEXT
Study 
Assessments1
Screen2
Day 
1 
C1
Day 
8 C1
Day 
15 
C1
Day 
1 
C2
Day 
15 
C2
D1 of C3-C16
End 
of 
Study
3-
Month 
Off-
study 
Follow-
up
HBV/HCV tests
X
Section 7.1.2.3,  Dose Expansion Every 3 Weeks Dosing Schedule for Other 
Hematologic Malignancies
PREVIOUS TEXT
Study Assessments1
Screen2
Day 1 
C1
Day 8 
C1
Day 15 
C1
Day 1 
C2
D1 of C3-C16
End 
of 
Study
3-
Month 
Off-
study 
Follow-
up
Serum (soluble BCMA) 
X14
X14
Serum 
(cytokines/chemokines)
X15
X15
X15
Predose and EOI 
on D1 of each 
cycle
X


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Study 
Assessments1
Screen2
Day 1 C1
Day 8 C1
Day 15 
C1
Day 1 C2
D1 of C3-C16
End 
of 
Study
3-
Month 
Off-
study 
Follow-
up
Survival Status
X24
Subsequent 
Treatment
X24
14. A single sBCMA sample will be collected at screening.  On C2D1 sBCMA will be collected at predose (within 
30 minutes prior to SOI) and at EOI (5 minutes).
REVISED TEXT
Study Assessments1
Screen2
Day 1 
C1
Day 8 
C1
Day 15 
C1
Day 1 
C2
D1 of C3-C16
End 
of 
Study
3-
Month 
Off-
study 
Follow-
up
Serum (soluble BCMA) 
X14
X14
X14
Serum 
(cytokines/chemokines)
X15
X15
X15
Predose and EOI 
on D1 of each 
cycle
X
Study 
Assessments1
Screen2
Day 1 C1
Day 8 C1
Day 15 
C1
Day 1 C2
D1 of C3-C16
End 
of 
Study
3-
Month 
Off-
study 
Follow-
up
Survival Status
X25
Subsequent 
Treatment
X25
14. A single sBCMA sample will be collected at screening.  C1D1 predose (within 30 minutes prior to SOI).  On 
C2D1 sBCMA will be collected at predose (within 30 minutes prior to SOI) and at EOI (5 minutes).
NEW TEXT
Study 
Assessments1
Screen2
Day 1 C1
Day 8 C1
Day 15 
C1
Day 1 C2
D1 of C3-C16
End of 
Study
3-
Month 
Off-
study 
Follow-
up
HBV/HCV tests
X


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Tumor biopsy 
for BCMA 
expression
X24
24. Archival or fresh tissue required for BCMA testing.  Refer to Section 5.2.1 Inclusion Criterion #4 for eligibility 
criteria. 
Section 7.1.2.4,  Dose Expansion Weekly Dosing Schedule for Other 
Hematologic Malignancies
PREVIOUS TEXT
Study Assessments1
Screen2
Day 
1 
C1
Day 
8 
C1
Day 
15 
C1
Day 
1 
C2
Day 
15 
C2
D1 of C3-C16
End 
of 
Study
3-
Month 
Off-
study 
Follow-
up
Serum (soluble BCMA) 
X13
X13
X13
X13
X13
X13
Serum 
(cytokines/chemokines)
X14
X14
X14
X14
X14
Predose and EOI on D1 of 
each cycle
X
Study 
Assessments1
Screen2
Day 
1 
C1
Day 
8 C1
Day 
15 
C1
Day 
1 
C2
Day 
15 
C2
D1 of C3-C16
End 
of 
Study
3-
Month 
Off-
study 
Follow-
up
Survival Status
X23
Subsequent 
Treatment
X23
13. A single sample for sBCMA will be collected at screening, on C1D8 predose, and at the End of Study visit.  
sBCMA samples will also be collected on C1D1 at EOI (5 minutes).  On C1D15 and C2D1 collect at 
predose (within 30 minutes prior to SOI) and EOI (5 minutes)
REVISED TEXT
Study Assessments1
Screen2
Day 
1 
C1
Day 
8 
C1
Day 
15 
C1
Day 
1 
C2
Day 
15 
C2
D1 of C3-C16
End 
of 
Study
3-
Month 
Off-
study 
Follow-
up
Serum (soluble BCMA) 
X13
X13
X13
X13
X13
X13
Serum 
(cytokines/chemokines)
X14
X14
X14
X14
X14
Predose and EOI on D1 of 
each cycle
X


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Study 
Assessments1
Screen2
Day 
1 
C1
Day 
8 C1
Day 
15 
C1
Day 
1 
C2
Day 
15 
C2
D1 of C3-C16
End 
of 
Study
3-
Month 
Off-
study 
Follow-
up
Survival Status
X2325
Subsequent 
Treatment
X2325
13. A single sample for sBCMA will be collected at screening, on C1D8 predose, and at the End of Study visit.  
sBCMA samples will also be collected on C1D1 at predose (within 30 minutes prior to SOI) and EOI (5 
minutes).  On C1D15 and C2D1 collect at predose (within 30 minutes prior to SOI) and EOI (5 minutes)
NEW TEXT
Study 
Assessments1
Screen2
Day 
1 
C1
Day 
8 C1
Day 
15 
C1
Day 
1 
C2
Day 
15 
C2
D1 of C3-C16
End 
of 
Study
3-
Month 
Off-
study 
Follow-
up
HBV/HCV tests
X
Study 
Assessments1
Screen2
Day 
1 
C1
Day 
8 C1
Day 
15 
C1
Day 
1 
C2
Day 
15 
C2
D1 of C3-C16
End 
of 
Study
3-
Month 
Off-
study 
Follow-
up
Tumor biopsy 
for BCMA 
expression
X23
23. Arcived or fresh tissue required for BCMA testing.  Refer to Section 5.2.1 Inclusion Criterion #4 for eligibility 
criteria. 
Section 7.3.6,  Laboratory Assessments, Table 15, List of Clinical 
Laboratory Tests
PREVIOUS TEXT
Glucose, fasting
Total carbon 
dioxide (CO2)
Gamma glutamyl transferase 
(GGT)
Albumin
Magnesium
Phosphorous
Creatinine kinase (CK)
LDH


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Serum Creatine Phosphokinase (CPK)
Human Immunodeficiency virus (HIV)
REVISED TEXT
Glucose, fasting
Total carbon 
dioxide (CO2)
Gamma glutamyl transferase 
(GGT)
Albumin
Magnesium
Phosphorous
Creatinine kinase (CK)
LDH
Serum Creatine Phosphokinase (CPK)
Human Immunodeficiency virus (HIV)
Section 7.4.1, Blood Sample Collection for Pharmacokinetics
PREVIOUS TEXT
Blood samples of approximately 1 mL for pharmacokinetic (PK) analysis of 
GSK2857916 (ADC and total antibody) and cys-mcMMAF will be collected at the time
points indicated in the Time and Events Tables (Section 7.1).  Each PK sample should be 
collected as close as possible to the planned time relative to the dose (i.e., time zero) 
administered to the subject 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 Study Procedures Manual (SPM).  
REVISED TEXT
Blood samples of approximately 1 5 mL for pharmacokinetic (PK) analysis of 
GSK2857916 (ADC and total antibody) and cys-mcMMAF will be collected at the time 
points indicated in the Time and Events Tables (Section 7.1).  Each PK sample should be 
collected as close as possible to the planned time relative to the dose (i.e., time zero) 
administered to the subject 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 Study Procedures Manual (SPM).  Blood volumes for PK samples are 
outlined in Appendix 10 (Section 17.10).


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Section 10, Concomitant Medications and Non-Drug Therapies
NEW TEXT
Concomitant dosing of GSK2857916 with strong Pgp inhibitors should be avoided unless 
considered medically necessary (See Appendix 11 for list of relevant Pgp inhibitors).
If future changes are made to the list of permitted/prohibited medications, formal 
documentation will be provided by GSK and stored in the study file.  The SPM will be 
updated to include this information. Any such changes will be communicated to the 
investigative sites in the form of a letter.
Section 17.10, Appendix 10: Blood Requirements
PREVIOUS TEXT
Blood Requirements in Dose Escalation and Dose Expansion Cohorts for All Lab 
Tests, Except PK
Test Sample
Sample 
Volume
Requirements for 
Screening – Cycle 1
Requirements for 
Subsequent Cycles
Hematology
5 ml
10-25 ml
5 ml
Chemistry
5 ml
15-20 ml
5 ml
Coagulation
5 ml
10-20 ml
5 ml
Hgb A1c
5 ml
5 ml
SPEP/UPEP
6 ml
6 ml
6 ml
CRP
1 ml
1-2 ml
1 ml
B2 microglobulin
1 ml
1-2 ml
1 ml
Kappa, lambda free LC, FLC
1 ml
1 ml
1 ml
Immunoglobulin levels (IgG, 
IgA, IgM)
6 ml
6 ml
6 ml
Plasma collection for cfDNA 
and circulating cytokines
5 ml
5 ml
5 ml
Hepatitis B, Hepatitis C
3 ml
3 ml
HIV
5 ml
5 ml
CK-MB
3 ml
6 ml
3 ml
Anti-Drug Antibody
3 ml
3 ml
3 ml
BNP
3 ml
3 ml
Troponin
2.5 ml
5 ml
2.5 ml
TBNK
3 ml
3 ml
3 ml
sBCMA1
1 ml
6 ml
6 ml
PGx2
6 ml
6 ml
Total Volume
100-132 ml
52.5 ml
1Calculation reflects blood drawn for sBCMA measurement in a MM subject
2 Dose expansion only


2012N155299_05
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Blood Requirements for PK
PK Schedule
Sample 
Volume
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 5 
Total 
Volume
Escalation Every 3 Weeks
3 ml
27 ml
6 ml
6 ml
39 ml
Escalation Weekly
3 ml
33 ml
6 ml
6 ml
45 ml
Expansion Every 3 Weeks 
MM
3 ml
6 ml
6 ml
6 ml
6 ml
24 ml
Expansion Every 3 Weeks 
Other Hematologic 
Malignancies
3 ml
12 ml
6 ml
6 ml
6 ml
30 ml
Expansion Weekly MM
3 ml
24 ml
12 ml
12 ml
6 ml
54 ml
Expansion Weekly 
Other Hematologic 
Malignancies
3 ml
24 ml
12 ml
12 ml
6 ml
54 ml
Total Blood Requirements
Schedule
Screening + Cycle 1
Subsequent Cycles
Escalation Every 3 Weeks
127-159 ml
58.5 ml
Escalation Weekly
133-165 ml
58.5 ml
Expansion Every 3 Weeks
106-144 ml
58.5 ml
Expansion Weekly
124-156 ml
58.5-64.5 ml
REVISED TEXT
Blood Requirements in Dose Escalation and Dose Expansion Cohorts for All Lab 
Tests, Except PK
Test Sample
Sample 
Volume
Requirements for 
Screening – Cycle 1
Requirements for 
Subsequent Cycles
Hematology
5 ml
10-25 ml
5 ml
Chemistry
5 ml
15-20 ml
5 ml
Coagulation
5 ml
10-20 ml
5 ml
Hgb A1c
5 ml
5 ml
SPEP/UPEP
6 ml
6 ml
6 ml
CRP
1 ml
1-2 ml
1 ml
B2 microglobulin
1 ml
1-2 ml
1 ml
Kappa, lambda free LC, FLC
1 ml
1 ml
1 ml
Immunoglobulin levels (IgG, 
IgA, IgM)
6 ml
6 ml
6 ml
Plasma collection for cfDNA 
and circulating cytokines
5 ml
5 ml
5 ml


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Test Sample
Sample 
Volume
Requirements for 
Screening – Cycle 1
Requirements for 
Subsequent Cycles
Hepatitis B, Hepatitis C
3 ml
3 ml
HIV
5 ml
5 ml
CK-MB
3 ml
6 ml
3 ml
Anti-Drug Antibody
3 ml
3 ml
3 ml
BNP
3 ml
3 ml
Troponin
2.5 ml
5 ml
2.5 ml
TBNK
3 ml
3 ml
3 ml
sBCMA1
1 ml
6 ml
6 ml
PGx2
6 ml
6 ml
Total Volume
100-132 ml
52.5 ml
1Calculation reflects blood drawn for sBCMA measurement in a MM subject
2 Dose expansion only
Blood Requirements for PK 
PK Schedule
Sample 
Volume
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 5 
Total 
Volume
Escalation Every 3 Weeks
3 ml
27 ml
6 ml
6 ml
39 ml
Escalation Weekly
3 ml
33 ml
6 ml
6 ml
45 ml
Expansion Every 3 Weeks 
MM
3 ml
6 ml
6 ml
6 ml
6 ml
24 ml
Expansion Every 3 Weeks 
Other Hematologic 
Malignancies
3 ml
12 ml
6 ml
6 ml
6 ml
30 ml
Expansion Weekly MM
3 ml
24 ml
12 ml
12 ml
6 ml
54 ml
Expansion Weekly 
Other Hematologic 
Malignancies
3 ml
24 ml
12 ml
12 ml
6 ml
54 ml
Total Blood Requirements
Schedule
Screening + Cycle 1
Subsequent Cycles
Escalation Every 3 Weeks
127-159 ml
58.5 ml
Escalation Weekly
133-165 ml
58.5 ml
Expansion Every 3 Weeks
106-144 ml
58.5 ml
Expansion Weekly
124-156 ml
58.5-64.5 ml


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Blood Requirements for All Lab Tests, Except PK
Test Sample
Sample 
Volume
Screening
Cycle 1
Each 
Subsequent 
Cycle
Hematology
5 ml
5 ml
10-15 ml
5 ml
Chemistry
5 ml
5 ml
15-20 ml
5 ml
Coagulation
5 ml
5 ml
10-15 ml
5 ml
SPEP
6 ml
6 ml
6 ml
CRP
1 ml
1 ml
1 ml
B2 Microglobulin
1 ml
1 ml
1 ml
Kappa, lambda free 
LC, FLC
1 ml
1 ml
1 ml
IgG, IgA, IgM
6 ml
6 ml
6 ml
cfDNA
10 ml
10 ml
Cytokines
3 ml
6 ml
6 ml
HBV/HCV
3 ml
3 ml
CK-MB
3 ml
3 ml
3 ml
3 ml
ADA
3 ml
3 ml
0-3 ml
BNP
3 ml
3 ml
Troponin
2.5 ml
2.5 ml
2.5 ml
2.5 ml
TBNK
3 ml
3 ml
3 ml
sBCMA
1 ml
5 ml
1-2 ml
Pregnancy Test1
2 ml
2 ml
0-2 ml
Total
59.5 ml
51.5-66.5 ml
45.5-51.5 ml
1. Required for women of childbearing potential
Dose Escalation:  Weekly for Multiple Myeloma
Test Sample
Sample 
Volume
Screening
Cycle 1
Each 
Subsequent 
Cycle
Hematology
5 ml
5 ml
10-15 ml
5 ml
Chemistry
5 ml
5 ml
15-20 ml
5 ml
Coagulation
5 ml
5 ml
10-15 ml
5 ml
SPEP
6 ml
6 ml
6 ml
CRP
1 ml
1 ml
1 ml
1 ml
B2 Microglobulin
1 ml
1 ml
1 ml
1 ml
Kappa, lambda free 
LC, FLC
1 ml
1 ml
1 ml
IgG, IgA, IgM
6 ml
6 ml
6 ml
cfDNA
10 ml
10 ml
Cytokines
3 ml
6 ml
6 ml
HBV/HCV
3 ml
3 ml
CK-MB
3 ml
3 ml
3 ml
3 ml
ADA
3 ml
3 ml
3 ml
0-3 ml


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Test Sample
Sample 
Volume
Screening
Cycle 1
Each 
Subsequent 
Cycle
BNP
3 ml
3 ml
Troponin
2.5 ml
2.5 ml
2.5 ml
2.5 ml
TBNK
3 ml
3 ml
3 ml
sBCMA
1 ml
6 ml
1-2 ml
Pregnancy Test1
2 ml
2 ml
0-2 ml
Total
59.5 ml
57.5-72.5 ml
45.5-51.5 ml
1. Required for women of childbearing potential
Dose Expansion:  Every 3 Weeks for Multiple Myeloma
Test Sample
Sample 
Volume
Screening
Cycle 1
Each 
Subsequent 
Cycle
Hematology
5 ml
5 ml
10-15 ml
5 ml
Chemistry
5 ml
5 ml
10-15 ml
5 ml
Coagulation
5 ml
5 ml
10-15 ml
5 ml
SPEP
6 ml
6 ml
6 ml
CRP
1 ml
1 ml
1 ml
B2 Microglobulin
1 ml
1 ml
1 ml
Kappa, lambda free 
LC, FLC
1 ml
1 ml
1 ml
IgG, IgA, IgM
6 ml
6 ml
6 ml
cfDNA
10 ml
10 ml
Cytokines
3 ml
6 ml
6 ml
HBV/HCV
3 ml
3 ml
CK-MB
3 ml
3 ml
3 ml
3 ml
ADA
3 ml
3 ml
0-3 ml
BNP
3 ml
3 ml
Troponin
2.5 ml
2.5 ml
2.5 ml
2.5 ml
TBNK
3 ml
3 ml
3 ml
sBCMA
1 ml
2 ml
1-2 ml
Pregnancy Test1
2 ml
2 ml
0-2 ml
PgX
6 ml
6 ml
Total
59.5 ml
49.5-64.5 ml
45.5-51.5 ml
1. Required for women of childbearing potential


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Dose Expansion:  Weekly for Multiple Myeloma
Test Sample
Sample 
Volume
Screening
Cycle 1
Each 
Subsequent 
Cycle
Hematology
5 ml
5 ml
10-15 ml
5 ml
Chemistry
5 ml
5 ml
10-15 ml
5 ml
Coagulation
5 ml
5 ml
10-15 ml
5-10 ml
SPEP
6 ml
6 ml
6 ml
CRP
1 ml
1 ml
1 ml
B2 Microglobulin
1 ml
1 ml
1 ml
Kappa, lambda free 
LC, FLC
1 ml
1 ml
1 ml
IgG, IgA, IgM
6 ml
6 ml
6 ml
cfDNA
10 ml
10 ml
Cytokines
3 ml
6 ml
6 ml
HBV/HCV
3 ml
3 ml
CK-MB
3 ml
3 ml
3 ml
3 ml
ADA
3 ml
3 ml
0-3 ml
BNP
3 ml
3 ml
Troponin
2.5 ml
2.5 ml
2.5 ml
2.5 ml
TBNK
3 ml
3 ml
3 ml
sBCMA
1 ml
1 ml
1-2 ml
Pregnancy Test1
2 ml
2 ml
0-2 ml
PgX
6 ml
6 ml
Total
59.5 ml
49.5-64.5 ml
45.5-56.5 ml
1. Required for women of childbearing potential
Dose Expansion:  Every 3 Weeks for Other Hematologic Malignancies
Test Sample
Sample 
Volume
Screening
Cycle 1
Each 
Subsequent 
Cycle
Hematology
5 ml
5 ml
10-15 ml
5 ml
Chemistry
5 ml
5 ml
10-15 ml
5 ml
Coagulation
5 ml
5 ml
10-15 ml
5 ml
CRP
1 ml
1 ml
1 ml
B2 Microglobulin
1 ml
1 ml
1 ml
IgG, IgA, IgM
6 ml
6 ml
6 ml
cfDNA
10 ml
10 ml
Cytokines
3 ml
6 ml
6 ml
HBV/HCV
3 ml
3 ml
CK-MB
3 ml
3 ml
3 ml
3 ml
ADA
3 ml
3 ml
0-3 ml
BNP
3 ml
3 ml
Troponin
2.5 ml
2.5 ml
2.5 ml
2.5 ml
TBNK
3 ml
3 ml
3 ml


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Test Sample
Sample 
Volume
Screening
Cycle 1
Each 
Subsequent 
Cycle
sBCMA
1 ml
1 ml
0-2 ml
Pregnancy Test1
2 ml
2 ml
0-2 ml
PgX
6 ml
6 ml
Total
52.5 ml
48.5-63.5 ml
37.5-44.5 ml
1. Required for women of childbearing potential
Dose Expansion:  Weekly for Other Hematologic Malignancies
Test Sample
Sample 
Volume
Screening
Cycle 1
Each 
Subsequent 
Cycle
Hematology
5 ml
5 ml
10-15 ml
5 ml
Chemistry
5 ml
5 ml
10-15 ml
5-10 ml
Coagulation
5 ml
5 ml
10-15 ml
5 ml
CRP
1 ml
1 ml
1 ml
B2 Microglobulin
1 ml
1 ml
1 ml
IgG, IgA, IgM
6 ml
6 ml
6 ml
cfDNA
10 ml
10 ml
Cytokines
3 ml
6 ml
6 ml
HBV/HCV
3 ml
3 ml
CK-MB
3 ml
3 ml
3 ml
3 ml
ADA
3 ml
3 ml
3 ml
0-3 ml
BNP
3 ml
3 ml
Troponin
2.5 ml
2.5 ml
2.5 ml
2.5 ml
TBNK
3 ml
3 ml
3 ml
sBCMA
1 ml
5 ml
0-2 ml
Pregnancy Test1
2 ml
2 ml
0-2 ml
PgX
6 ml
6 ml
Total
52.5 ml
55.5-70.5 ml
37.5-49.5 ml
1. Required for women of childbearing potential


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Blood Requirements for PK
PK Schedule
Sample 
Volume
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 5 
Total 
Volume
Escalation Every 3 Weeks
5 ml
60 ml
10 ml
10 ml
80 ml
Escalation Weekly
5 ml
80 ml
10ml
10 ml
100 ml
Expansion Every 3 Weeks 
MM
5 ml
20 ml
20 ml
20 ml
20 ml
80 ml
Expansion Weekly MM
5 ml
20 ml
10 ml
10 ml
10 ml
50 ml
Expansion Every 3 Weeks 
Other Hematologic 
Malignancies
5 ml
40 ml
20 ml
20 ml
10 ml
90 ml
Expansion Weekly 
Other Hematologic 
Malignancies
5 ml
40 ml
20 ml
20 ml
10 ml
90 ml
Total Blood Requirements
Schedule
Screening
Cycle 1
Each Subsequent 
Cycle
Escalation Every 3 Weeks 
MM
59.5 ml
111.5-126.5 ml
45.5-61.5 ml
Escalation Weekly MM
59.5 ml
137.5-152.5 ml
45.5-61.5 ml
Expansion Every 3 Weeks 
MM
59.5 ml
69.5-84.5 ml
45.5-61.5 ml
Expansion Weekly MM
59.5 ml
69.5-84.5 ml
45.5-66.5 ml
Expansion Every 3 Weeks 
Other Hematologic 
Malignancies
52.5 ml
88.5-103.5 ml
37.5-64.5 ml
Expansion Weekly Other
Hematologic Malignancies
52.5 ml
95.5-110.5 ml
37.5-69.5 ml
The Study Procedures Manual will be updated with new information if changes in blood 
volumes are required.


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Section 17.11, Appendix 11: Pgp Inhibitors
NEW TEXT
Amiodarone
Atorvastatin
Azithromycin
Carvedilol
Clarithromycin
Dronedarone
Fluvoxamine
Indinavir
Indinavir and Ritonavir
Itraconazole
Ketonazole
Lapatinib
Lopinavir and Ritonavir
Nicardipine
Quinidine
Ranolazine
Ritonavir
Saquinavir and Ritonavir
Telaprevir
Verapamil
Valspodar
The Study Procedures Manual will be updated if changes to the Pgp inhibitor list is 
required.


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16.11.3.
Amendment 3
Where the Amendment Applies
Canada
Summary of Amendment Changes with Rationale
1. Section 4.2, Preparation/Handling/Storage of GSK2867916 Investigational 
Product

Rationale: Health Canada requested change to the amount of time prepared 
product can be kept under refrigerated conditions from 24 hours to 8 hours as 
the product does not contain an antimicrobial preservative
List of Specific Changes
Section 4.2,  Preparation/Handing/Storage of GSK2857916 Investigational 
Product
PREVIOUS TEXT
Preparation
GSK2857916 Solution for Infusion, 20 mg/mL is supplied as a frozen liquid (Lot# 
132373860).  Before use, thaw each vial of GSK2857916 for Infusion, 20mg/mL, 1.5mL 
for up to 4 hours under refrigerated conditions, protected from light.  Following thawing, 
gently swirl the vial to ensure uniformity.  GSK2857916 should be diluted in normal 
saline (0.9%) to no more than 2 mg/mL and no less than 0.2 mg/mL.
The dosing solution of GSK2857916 can be held up to 24 hours under refrigerated 
conditions or 4 hours at room temperature (diluted drug product in bag) from a stability 
perspective, but should be used as soon as possible as the product does not contain an 
antimicrobial preservative.
REVISED TEXT
Preparation
GSK2857916 Solution for Infusion, 20 mg/mL is supplied as a frozen liquid (Lot# 
132373860).  Before use, thaw each vial of GSK2857916 for Infusion, 20mg/mL, 1.5mL 
for up to 4 hours under refrigerated conditions, protected from light.  Following thawing, 
gently swirl the vial to ensure uniformity.  GSK2857916 should be diluted in normal 
saline (0.9%) to no more than 2 mg/mL and no less than 0.2 mg/mL.
The dosing solution of GSK2857916 can be held up to 24 8 hours under refrigerated 
conditions or 4 hours at room temperature (diluted drug product in bag) from a stability 
perspective, but should be used as soon as possible as the product does not contain an 
antimicrobial preservative.


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16.11.4.
Amendment 4
Where the Amendment Applies
Amendment 4 applies to all sites in Canada, United Kingdom, and United States
Amendment Changes with Rationale
The protocol Amendment 2 dated 20 March 2014 (applied to all sites) and protocol 
Amendment 3 dated 05 May 2014 (applied to sites in Canada) are replaced by 
Amendment 4 with the effective date of 05 MAY 2016.
The following protocol changes have been implemented to include patient reported 
outcome instruments in the Part 2 multiple myeloma cohort and refine the lymphoma 
histologies eligible in Part 2 BCMA-expressing lymphoma cohort (the prior cohort name 
of “other hematologic malignancies” will be replaced with “lymphomas”; this revision 
will be referenced throughout the protocol. Additionally the requirement for 60% of 
tumor cells staining positive for BCMA expression was removed. The total number of 
subjects that may be enrolled is presented by a range of 80 to 95 to provide an updated 
estimate based on the number of subjects who enrolled at the time of the amendment.  
Additional modifications include: changing the time-point specific blood specimens are 
collected for baseline/pre-treatment immunogenicity and biomarker measurements, and 
the visit window for certain assessments. The primary and secondary medical monitors 
were updated and study treatment dose modification revisions were made for Grade 3 
ocular toxicities. 
Original text displayed as strikethrough indicates replaced or removed text. New text is 
displayed as underline. Revisions within tables will either be presented with the entire 
table or displayed as text (i.e., for larger tables). Revisions to figures will be displayed 
first by the old figure and then followed by the new figure. Typos or minor word changes 
will not be presented.
Summary of Changes
1. Medical Monitor/Sponsor Contact Information
Role
Name
Day Time 
Phone 
Number
After-hours 
Phone/Cell/
Pager 
Number
GSK Address
Primary 
Medical 
Monitor
MD
GlaxoSmithKline
1250 South Collegeville Road
Mailstop UP1450 UP-4300
Collegeville, PA 19426, USA
Secondary 
Medical 
Monitor
MD
 
MD
GlaxoSmithKline
1250 South Collegeville Road
Mailstop UP4315UP4300
Collegeville, PA 19436, USA
PPD
PPD
PPD
PPD
PPD
PPD


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2. Protocol Synposis
RATIONALE: This is a FTIH study that will assess the safety, pharmacokinetics (PK), 
pharmacodynamics (PD) and therapeutic potential of GSK2857916 in multiple myeloma 
(MM) and other hematologic malignancies lymphomas that express BCMA.
The hypothesis is that GSK2857916 can be safely administered to subjects with BCMA 
positive malignancies at doses where target engagement can be demonstrated.  This study 
will determine if adequate target engagement of BCMA receptors translates into clinical 
benefit for subjects with MM and other BCMA positive hematologic malignancies
lymphomas.
OBJECTIVES: 
Secondary

To evaluate the 
pharmacokinetic (PK) 
profile of GSK2857916 and 
the breakdown product cys-
mcMMAF) after 
intravenous (IV) single and 
repeat dose administration 
in subjects with 
relapsed/refractory MM and 
other BCMA expressing 
hematologic malignancies
lymphomas

GSK2857916 and cys-mcMMAF PK parameters 
following IV single and repeat dose administration 
during dose escalation as data permit (e.g., AUCs 
Cmax, tmax, CL, VSS, t½ [single dose], Cmax and 
Ctrough [repeat dose]). GSK2857916 population 
PK parameters in expansion cohorts at the RP2 
dose (e.g. clearance (CL), volume of distribution 
(Vd)), and relevant covariates which may 
influence exposure (e.g. age, weight, or disease-
related covariates e.g. BCMA expression) 

To assess anti-drug 
antibody (ADA)formation 
after IV single and repeat 
dose administration of 
GSK2857916

ADA incidence and titers after single and repeat 
IV dosing of GSK2857916

To explore the initial anti-
tumor activity of 
GSK2857916 in subjects 
with relapsed/refractory 
MM and other BCMA 
expressing hematologic 
malignancies lymphomas

Clinical activity measured as Overall Response 
Rate (ORR) which is defined as follows:
o
For MM: the percentage of subjects 
achieving confirmed partial response or 
better (PR) 
o
In addition, the percentage of subjects with 
minimal response (MR) will be assessed 
for clinical benefit rate (CBR) (Appendix 
1)
o
For Other Hematologic Malignancies 
Lymphomas: the percentage of subjects 
achieving PR or better (PR) (Appendix 


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2Appendix 2) (Appendix 3)
Exploratory 

To evaluate PD markers in 
MM after treatment with 
GSK2857916

sBCMA levels, BCMA receptor occupancy and 
cell death markers in subjects with MM. 

To explore relationships of 
GSK2857916 plasma 
concentrations/exposure 
with pharmacodynamics 
(PD), safety and clinical 
activity 

Relationship between receptor occupancy, tumor 
cell death markers, sBCMA and GSK2857916 
plasma PK parameters;

Relationship between safety/clinical activity (e.g. 
ORR) and GSK2857916  PK parameters 

To characterize the 
relationship between 
clinical response and other 
biologic tumor 
characteristics (DNA, 
protein analysis)

BCMA expression levels on malignant cells as 
measured by IHC and/or flow cytometry in tumor 
tissue, serum sBCMA levels and their relationship 
to clinical response

To investigate the 
relationship between genetic 
variants in the host and 
response to GSK2867916
study medicine, or 
susceptibility, severity and 
progression of disease.

Relationship between host genetic variation and 
response to GSK2867916 study medicine or 
susceptibility, severity and progression of disease

To explore the effect of 
GSK2857916 on bone 
pain/fatigue and HRQoL in 
subjects with 
relapsed/refractory MM
(Part 2)

Changes from baseline in bone pain/fatigue and 
analgesic use as measured by the eDiary

Interviews with subjects to further characterize 
changes in bone pain/fatigue and impacts on 
HRQoL
Rationale for Change: update the objectives and endpoints to align with the other 
hematologic malignancies to be restricted to lymphomas and the inclusion of fatigue and 
bone pain quality of life instruments in Part 2 multiple myeloma cohort. Also allow for 
genetic research to include analyses of genetic variants with disease susceptibility, 
severity, and progression of disease. 


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STUDY DESIGN: This study is an open-label, dose escalation Phase I FTIH study to 
determine the RP2 dosing regimen of GSK2857916.  The recommended dose and 
schedule will be selected based on the safety, pharmacokinetic (PK), and 
pharmacodynamic (PD) profiles observed after administering the study drug to subjects 
with multiple myeloma (MM).  The study will consist of two parts and will enroll 
approximately 80-95 subjects.  The Part 1 dose escalation phase will characterize the 
safety and tolerability of respective dosing regimen for GSK2857916 utilizing the model 
based on the Neuenschwander continual reassessment method (N-CRM).  Initially, 
GSK2857916 will be administered via 60 min intravenous (IV) infusion once every three 
weeks (21 days = 1 cycle). After a MTD or recommended phase 2 dose (RP2D) has been 
established on the once every three weeks schedule, the safety, tolerability, and PK of 
once-weekly dosing of GSK2857916 for three consecutive weeks with 1 week rest (28 
days = 1 cycle) may be explored in an additional cohort(s). Part 2 will explore the safety, 
tolerability, PK, PD, and clinical activity of the RP2 dose of GSK2857916 identified in 
Part 1.  Subjects with MM (n=40) and lymphomas expressing BCMA (n=10) will be 
enrolled inexpansion cohort in Part 2. Futility analyses will be performed on the MM 
cohort after approximately 15, 22, 30 subjects have been enrolled. Sparse PK sampling 
will be collected to further characterize GSK2857916 exposures for the selected dose 
schedule.  Although not required for MM, subjects with other BCMA-positive 
hematologic malignancies lymphomas will be enrolled in Part 2 based upon the detection 
of positive BCMA staining of tumor cells in a prospective immunohistochemistry 
screening assay performed at a central laboratory.
NUMBER OF SUBJECTS: Approximately 80-95 subjects will be enrolled.
Up to 30 subjects with relapsed/refractory MM will be enrolled in Part 1, Schedule 1; 
Schedule 2, if explored, will enroll up to 15 additional subjects in Part 1.
Up to 40 subjects with relapsed/refractory MM and up to 10 subjects with other 
hematologic malignancies lymphomas expressing BCMA will be enrolled in Part 2.
INCLUSION CRITERIA
2.
Male or female, 18 years or older (at the time consent is obtained) and must have a 
body weight of at least 45 kg (99 lb).
4. Part 2/Other BCMA positive Hematologic Malignancies cohort: 
a.Subject with one of the following hematologic malignancies lymphomas:
Waldenstrom’s Macroglobulinemia (WM), Diffuse Large B-cell Lymphoma 
(DLBCL), or and chronic lymphocytic leukemia (CLL) follicular lymphoma 
(FL) that exhibits positive BCMA expression on tumor cells as determined by a 
central laboratory using a validated IHC assay. The BCMA positivity is defined 
as having approximately 60% of tumor cells staining positive for BCMA, and 
the staining intensity must be 2 on IHC scale 0-3.
Eligible subjects with BCMA positive malignancies lymphomas must also fulfill the 
prior treatment requirements as follows:


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b. DLBCL and WM: at least 2 prior lines of systemic therapy containing at least 
one line of chemo-immunotherapy with anti-CD20 antibody, and either has 
undergone stem cell transplant or is considered transplant ineligible.
c.FL: at least 2 prior lines of systemic therapy CLL: at least 2 prior lines of 
systemic therapies, and who are refractory to fludarabine, and failed (or are 
ineligible) for rituximab, ofatumumab and bendamustine.
6. Adequate organ system functions as defined in Table below:
General
Ca
1.1xULN 
Exclusion Criteria:
1.
Systemic anti-myeloma tumor therapy within 14 days, or plasmapheresis within 7 
days prior to the first dose of study drug.
17. Subjects with positive test for hepatitis C (HCV) infection are excluded regardless 
of viral load.  If hepatitis C antibody test is positive, a confirmatory polymerase chain 
reaction (PCR) or recombinant immunoblot assay (RIBA) test should be performed.  If 
the PCR or RIBA test is negative, subject is eligible for this trial.
Rationale for Changes: removed the minimum weight in Inclusion criterion 2 as that 
was required for the lowest doses administered during dose escalation. The Part 2 
hematologic malignancies were refined to include DLBCL and FL only based on the 
frequency of BCMA expression and the intensity of expression observed. 
PHARMACOKINETIC/ PHARMACODYNAMIC ASSESSMENT(S): 
In the Part 2 dose expansion phase in subjects with other BCMA positive lymphomas  
hematologic malignancies PK samples will be taken for both GSK2587916 and cys-
mcMMAF measurement according to the Time and Events Tables in Section 7.17.1.
CLINICAL ACTIVITY ASSESSMENT:
For Other Hematologic Malignancies Lymphomas: the percentage of subjects with 
confirmed CR, PR, as described in the Revised Response Criteria for Malignant 
Lymphoma (Appendix 2). and for CLL Appendix 3).
TRANSLATIONAL RESEARCH
Pharmacodynamic assessments will include evaluation of tumor tissue by flow cytometry 
and immunohistochemistry (IHC) for plasma cell expression of free BCMA receptors and 
GSK2857916 bound receptors, cell cycle markers, as well as apoptosis markers on tumor 
cells, to understand anti-tumor responses. IHC markers may include but will not be 
limited to BCMA, Blimp1, CD38, CD45, cys-mcMMAF, CC3, PH3, and MPM-2.  
Additionally, tumor tissue may be evaluated for any DNA /RNA changes correlating with 
response.  Serum levels of free and GSK2857916 bound sBCMA will be assessed by 
Meso-Scale Discovery immunoassay and correlated with clinical outcome to treatment 
with GSK2857916.  Cytokines and, chemokines, and cfDNA will also be measured; cell-
free deoxyribonucleic acid (cfDNA) may be measured.  


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Leukocyte population will be characterized and may be correlated with clinical outcome.
Pharmacogenetic A genetics samples will be collected in Part 2 and may be used to 
investigate variability in response that may be attributable to host genetic variation, if it 
emerges during this clinical study or a series of clinical studies of GSK2857916 
(Appendix 7). Further, the genetic sample may be used to investigate the relationship 
between genetic variation and disease (susceptibility, severity or progression).
Rationale for Changes: as cfDNA analyses may not occur the language was revised 
accordingly. Sample collected for genetic analysis may be used to investigate 
relationships between genetic variations and disease associated parameters in addition to 
response to GSK2857916.
PATIENT REPORTED OUTCOMES
Part 2/MM cohort: changes in symptoms and health-related quality of life (HRQoL) will 
be assessed with the use of the Bone Pain/Fatigue diary.
Rationale for Change: inclusion of HRQoL assessments in Part 2 MM cohort will 
provide a preliminary assessement of patient report for affects of GSK2857916 on bone 
pain and fatigue. 
3. Section 1.1 Background
BCMA is expressed in various B-cell malignancies, including MM.  The expression 
levels in MM vary from patient to patient, but our studies demonstrate that all patients 
tested express detectable levels of BCMA protein on their tumor cells. BCMA expression 
varies between MM patients and GlaxoSmithKline (GSK) studies have shown that in 
samples taken from MM patients (N=45), 31% have low expression, 38% moderate 
expression and 31% high expression of BCMA as detected by immunohistochemistry 
(IHC).  BCMA was also analyzed by flow cytometry in tumor cells from 48 MM patients 
which aligned well with IHC results. In addition, other B-cell malignancies including 
Follicular Lymphoma (FL) [Basso, 2005; GSKin-house data], Diffuse Large B-Cell 
Lymphoma (DLBCL), Large B-Cell Lymphoma (LBCL), Chronic Lymphocytic 
Leukemia (CLL) and Waldenstrom’s Macroglobulinemia (WM) [Montes-Moreno, 2012] 
[Elsawa, 2006] [Endo, 2007] were reported to express BCMA at varying 
frequencies;DLBCL and FL were among the B-cell hematologic malignancies exhibiting 
the highest frequency of BCMA expression.
A soluble form of BCMA has also been reported [Sanchez, 2012].  Higher amounts of 
this soluble form were found in supernatants isolated from cultures of MM-containing 
peripheral blood and bone marrow mononuclear cells compared to normal cells.  
Moreover, soluble BCMA (sBCMA) was higher in the sera of MM patients (n=209) 
compared to sera from age-matched, healthy controls (n=40; P < 0.0001).  Measurement 
of serum levels of BCMA was conducted by immunoassay to confirm the prevalence and 
level of sBCMA expression in MM.  Soluble BCMA is present in serum at a median 
concentration of 9.28 ng/mL (range 6.10-14.09 ng/mL) in healthy volunteers (N=38) and 
is elevated in the serum of MM patients (N = 44) to median of 148.64 ng/mL (range 2.40-
1062.48 ng/mL). 


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In addition, other B-cell malignancies including Diffuse Large B-Cell Lymphoma 
(DLBCL), Large B-Cell Lymphoma (LBCL), Chronic Lymphocytic Leukemia (CLL) 
and Waldenstrom’s Macroglobulinemia (WM) [Montes-Moreno, 2012] [Elsawa, 2006]
[Endo, 2007] have been reported to express BCMA at varying frequencies. 
The restricted normal tissue expression profile of BCMA, along with its upregulation and 
survival function in MM and other BCMA-positive cancers makes it an attractive target 
for a therapeutic antibody with direct cell killing activity. 
4. Section 1.3.2 Benefit Assessment
Currently there is no clinical evidence that treatment with GSK2857916 will result in 
any benefit to subjects.  However, based on data from non clinical studies there is a 
possibility that GSK2857916 might reduce tumor burden in subjects with MM and 
other BCMA positive hematologic malignancies lymphomas.
5. Section 1.3.3 Overall Benefit:Risk Conclusion
Overall, due to lack of any limited clinical experience with GSK2857916 benefit/risk 
cannot be asseesesed at this time.  The safety of subject is the primary objective of 
this study and adequate monitoring and guidance for dose reductions/stopping criteria 
are provided in the protocol to minimize risks associated with exposure to 
GSK2857916. 
6. Objectives(s), Endpoint(s) and Hypothesis
Objective
Endpoint
Primary

To determine safety, 
tolerability, maximum 
tolerated dose (MTD), and 
recommended phase (RP2) 
dose and schedule of 
GSK2857916 administered

Adverse events (AE) and changes in clinical signs 
and laboratory parameters 
Secondary 

To evaluate the 
pharmacokinetic (PK) 
profile of GSK2857916 and 
the breakdown product cys-
mcMMAF) after 
intravenous (IV) single and 
repeat dose administration 
in subjects with 
relapsed/refractory MM and 
BCMA expressing 
lymphomas

GSK2857916 and cys-mcMMAF PK parameters 
following IV single and repeat dose administration 
during dose escalation as data permit (e.g., AUCs 
Cmax, tmax, CL, VSS, t½ [single dose], Cmax and 
Ctrough [repeat dose]). GSK2857916 population 
PK parameters in expansion cohorts at the RP2 
dose (e.g. clearance (CL), volume of distribution 
(Vd)), and relevant covariates which may 
influence exposure (e.g. age, weight, or disease-
related covariates e.g. BCMA expression) 


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Objective
Endpoint

To assess anti-drug 
antibody (ADA)formation 
after IV single and repeat 
dose administration of 
GSK2857916

ADA incidence and titers after single and repeat 
IV dosing of GSK2857916

To explore the initial anti-
tumor activity of 
GSK2857916 in subjects 
with relapsed/refractory 
MM and BCMA expressing 
lymphomas

Clinical activity measured as Overall Response 
Rate (ORR) which is defined as follows:
o
For MM: the percentage of subjects 
achieving confirmed partial response or 
better (PR) 
o
In addition, the percentage of subjects with 
minimal response (MR) will be assessed 
for clinical benefit rate (CBR) (Appendix 
1)
o
For Other HematologicMalignancies
Lymphomas: the percentage of subjects 
achieving PR or better (PR) (Appendix 2
and Appendix 3)
Exploratory 

To evaluate PD markers in 
MM after treatment with 
GSK2857916

sBCMA levels, BCMA receptor occupancy and 
cell death markers in subjects with MM. 

To explore relationships of 
GSK2857916 plasma 
concentrations/exposure 
with pharmacodynamics 
(PD), safety and clinical 
activity 

Relationship between receptor occupancy, tumor 
cell death markers, sBCMA and GSK2857916 
plasma PK parameters;

Relationship between safety/clinical activity (e.g. 
ORR) and GSK2857916  PK parameters 

To characterize the 
relationship between 
clinical response and other 
biologic tumor 
characteristics (DNA, 
protein analysis)

BCMA expression levels on malignant cells as 
measured by IHC and/or flow cytometry in tumor 
tissue, serum sBCMA levels and their relationship 
to clinical response

To investigate the 
relationship between genetic 
variants in the host and 
response to GSK2857916 
study medicine or 
susceptibility, severity and 

Relationship between host genetic variation and 
response to GSK2857916 study medicine or 
susceptibility, severity and progression of disease


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Objective
Endpoint
progression of disease

To explore the effect of 
GSK2857916 on bone 
pain/fatigue and HRQoL in 
subjects with 
relapsed/refractory MM

Changes from baseline in bone pain/fatigue and 
analgesic use as measured by the eDiary

Interviews with subjects to further characterize 
changes in bone pain/fatigue and impacts on 
HRQoL
7. Section 3.1 Discussion of Study Design
This is a First Time in Human (FTIH), open-label, dose escalation trial consisting of two 
parts: a Part 1 dose escalation phase and a Part 2 expansion phase for safety, and clinical 
activity testing (Table 3 and Section 3.2). The study will enroll a total of approximately 
80-95 subjects with relapsed/refractory MM or other BCMA-expressing hematologic 
malignancieslymphomas.  The maximum dose to be administered in this trial will not 
exceed 5 mg/kg.
Part 1: Dose-escalation cohorts will characterize the safety, tolerability, PK, and PD of 
GSK2857916 given on a once every 21 days or a once weekly schedule. Only subjects 
with MM will be enrolled in Part 1 based on an N-CRM dose escalation model until 
MTD(s) or RP2D is/are established on an appropriate schedule(s).
Once an MTD1 or RP2D has been established on the once every 21-day (Schedule 1), the 
safety, tolerability, PK, and PD of once-weekly dosing (Schedule 2) of GSK2857916 
may be explored as an additional cohort(s). 
A smaller cohort of subjects with other BCMA positive hematologic malignancies
lymphomas (up to 10 subjects) will be enrolled based upon prospective detection of 
positive BCMA tumor cell expression as determined by a central laboratory using a 
validated IHC screening assay.  BCMA staining intensity of 2 (on scale 0-3) in 
approximately 60% tumor cells vs. control slides will be assessed for study entry at a 
central laboratory). Enrollment into the cohort for other hematologic malignancies will be 
initiated once the safety of the selected dose and schedule have been confirmed in the 
MM expansion cohort (i.e. when at least >15 MM patients have enrolled and been 
evaluated for at least one cycle).
8. Section 3.2 Study Schematic
Old Figure


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New Figure
MTD1
4
3
1
2
25% of MTD1/RP2D1
MTD2/RP2D2
BCMA-positive Lymphomas (n =≈10)
Multiple myeloma  (n ≈ 40)
PART 1: Dose Escalation
(n≈30)
PART 2: Expansion Cohorts 
(n≈50)
2
3
1
*Cohort size to increase, n≈3 if ≥Grade 2 
drug related toxicity reported
5-9
4
RP2D1


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Abbreviations: MTD=maximum tolerated dose; N-CRM= Neuenschwander Continual Reassessment 
Method; RP2D=recommended phase 2 dose
1.
Part 2 to initiate after  once every 3 week recommended dose is determined
2.
Dose escalation with once weekly schedule may commence in parallel to Part 2 expansion
Rationale for Changes: the figure was revised to illustrate that Part 2 will be initiated 
after a recommended dose for the once every three weeks schedule is determined. Dose 
escalation of the once weekly schedule if investigated may commence at any time during 
the conduct of the study.
9. Section 3.3 Part 1: Dose-Escalation Phase
After the MTD1 or RP2D is established for the once every three weeks Schedule 1, once 
weekly dosing of GSK2857916 (Schedule 2) may be evaluated prior to, or in parallel 
with the expansion phase as described in Section 3.3.2.  A weekly dosing regimen may be 
chosen for further evaluation if toxicity is felt to be related to Cmax and that equivalent 
or greater exposures in terms of AUC can be safely achieved with weekly dosing 
compared with the once every 3weeks dosing regimen.  
10. Section 3.3.1.2.1 Planned Dose Levels
Prior to the start of the study, projected dose levels on Schedule 1 (in mg/kg) are 0.03, 
0.06, 0.12, 0.24, 0.48, 0.96, 1.92, 2.8, 3.6, and 4.5 mg/kg; actual dose levels will be 
determined by N-CRM (Neuenschwander-Continuous Reassessment Method).  
Additional doses and schedules may be explored based on emerging safety, PK, and PD 
data. The maximum dose to be administered in this trial will not exceed 5 mg/kg.
11. Section 3.3.1.2.3 Bayesian Prior
A graphical presentation of the initial prior is displayed in Figure 1.  Doses are the 
projected doses.  Actual doses used during the conduct of the trial may vary. An 
intermediate prior will be derived based on the initial prior by FACTS (Version 2.3 or 
higher) from Tessella. The final prior is determined based on the intermediate prior and 
all available data.
12. Section 3.3.2 Dose Escalation on Schedule 2 (GSK2857916 administered once 
weekly x3, 1 week rest; 28 days = 1 cycle)

The once weekly dosing cohorts may be explored prior to, or in parallel with, 
enrollment to the expansion cohorts (Part 2).

Depending on emerging safety signals, the proposed weekly starting dose will be 
25% of MTD1 or RP2D1.  If the initial dose of 25% of MTD1 or RP2D1 is not 
tolerated, dose escalation on the weekly schedule will be terminated and enrollment 
into Schedule 2 will be closed.  If the starting dose is tolerated, escalation on the 
weekly schedule will continue at increments of 30% and will follow the N-CRM 
procedure until MTD2 or RP2D2 is reached. 
13. Section 3.4 RP2 Dose and Administration Schedule Selection for Part 2
This lower dose level, or an intermediate dose considered the BED, may be tested as the 
RP2 dose for further evaluation in Part 2.  Part 2 may start enrolling once Part 1 has 
completed enrollment of Schedule 1 (once every three weeks) and after the preliminary 


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PK and relevant PD data have been analyzed. The schedule selection for Part 2 (weekly 
vs. once every 3 weeks vs. an intermediate schedule) will be based on the information 
collected following administration of GSK2857916 on the respective schedules evaluated 
in Part 1. The once weekly schedule may be explored prior to or in parallel with the 
expansion cohorts. Data considered will include, but not be limited to,  relationships 
between safety and exposure, the PK profiles, as well as any emerging PD information, 
and early signs of clinical activity observed for each schedule evaluated in Part 1. If the 
once weekly schedule is explored prior to initiating Part 2, the chosen dosing regimen 
would need to provide evidence of the following in order to be the preferred schedule in 
Part 2:  a better safety and tolerability profile at an equivalent or higher dose, or greater 
clinical activity, or a more desirable PK profile (i.e. no evidence of target-mediated 
disposition observed over the dosing interval).  A preference might be given to the 
weekly schedule if at MTD1, the receptor occupancy levels are considered sub-optimal 
and/or saturation of soluble sBCMA is not maintained long enough on the every 3 weeks 
dosing schedule.
Part 2: Expansion Cohort:
(Note: For details on scheduled procedures in subjects given GSK2857916 in Part 2, refer 
to Time and Events Tables Section 7.1.2. The Time and Events Table for GSK2857916 
administered to MM subjects on Schedule 1 is represented in Section 7.1.2.1, and the 
Time and Events Table for GSK2857916 administered to MM subjects on Schedule 2 is 
represented in Section 7.1.2.2. Refer to Time and Events Tables Section 7.1.2.3 and 
Section 7.1.2.4 for GSK2857916 administered to subjects with other hematologic 
malignancies lymphomas on Schedule 1 or Schedule 2, respectively).
Once the RP2 dose and schedule have been selected, expansion cohorts will be enrolled 
in order to better characterize the safety profile of the selected dose and schedule.  

The Part 2 expansion will enroll up to 50 subjects as summarized below:
o
Multiple Myeloma cohort (up to 40 subjects)- no prospective screening of 
BCMA is required for enrollment

Futility analyses based on ORR will take place after approximately 
15, 22 and 30 subjects have been evaluated for response. Full 
details can be found in Section 13.6.2  

BCMA expression data and retrospective analysis will be 
performed on samples collected in the MM population

PRO will be collected via eDiary in the MM population in Part 2 
only

OtherBCMA positive lymphomas (defined as BCMA positive 
staining by IHC) hematologic malignancies (up to 10 subjects) –
prospective screening of  BCMA expression is required for 
enrollment


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14. Section 3.6.1 Rationale for Study; Section 3.6.2 Rationale for Populations
This study will assess the safety, PK, PD and the therapeutic potential of 
GSK2857916 in subjects with MM and other hematologic malignancies lymphomas 
that express BCMA.
This study will determine if adequate target engagement of BCMA receptors 
translates into clinical benefit for subjects with MM and otherBCMA positive 
hematologic malignancieslymphomas.
Subjects with lymphomas that exhibit BCMA expression have been selected as an 
exploratory cohort in this FTIH study; the frequency of BCMA expression in 
lymphomas is lower than that observed in MM, therefore prospective selection is 
required.  
The target population for this study includes subjects with relapsed/refractory MM to 
establish the dose and characterize safety, PK and PD of GSK2857916.  Subjects with 
otherBCMA expressing hematologic malignancies lymphomas will also be allowed 
on study after prospective screening by IHC demonstrates that BCMA is expressed on 
tumor cells. Potential subjects with other B-cell malignancieslymphomas who will be 
tested for BCMA expression prior to study entry include, subjects with the following 
diseases:  Diffuse Large B-Cell Lymphoma (DLBCL), , Folicullar Lymphoma (FL), 
Chronic Lymphocytic Leukemia (CLL) and Waldenstrom’s Macroglobulinemia who 
have that have failedprogressed after 2 prior lines of systemic therapy for a given 
disease.  
15. Section 3.6.4 Rationale for Endpoints
Markers showing significant correlation between baseline levels and clinical outcome 
may have predictive value and maybe further explored for utility in patient selection 
in future trials.
Anti-tumor activity will be explored to evaluate the potential for clinical benefit from 
GSK2857916 treatment. In addition, patient report outcomes will also be studied in 
Part 2 (MM subjects only)
Rationale for Changes: QoL measurements were included as exploratory endpoints 
In Part 2 multiple myeloma cohort in order to provide preliminary analyses of affects 
of treatment on fatigue and bone pain. Additionally, biomarker analyses in the 
BMA117159 may uncover markers that may be implemented for patient selection in 
future trials.
16. Section 3.9.8. Ocular Toxicity and Stopping Criteria
All subjects will be advised to use prednisolone phosphate 1% or dexamethasone 
0.1% eye drop 4 times a day (QID) for 4 days starting 1 day prior to each dose. 
Additional use of lubrication eye drops (artificial tears) QID PRN throughout the trial 
is recommended, especially if subject develops any ocular symptoms. Subjects who 
develop Grade 3 ocular or corneal toxicity will be allowed to continue study 


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treatment after resolution to Grade 1; each case will be discussed individually 
between the investigator and the Medical Monitor. Subjects who develop Grade 3 4 
ocular or corneal toxicity will be permanently removed from study. Refer to Section 
3.10.2 for futher guidance.
Rationale for Change: The requirement to permanently discontinue GSK2857916 
for Grade 3 ocular toxicity was revised to require study treatment to be interrupted 
and to allow for these events to be discussed with regard to type of event and the 
duration of time for the event to resolve to Grade 1 or to baseline. If study treatment 
resumes, the dose will be reduced by at least 25% of the dose that was administered 
when event occurred.
17. Section 3.10.2  Predicted Toxicities and Proposed Dose Adjustments/Stopping 
Criteria
Grade 2 Ocular Toxicity: Further treatment Permanently discontinue treatment with 
GSK2857916 only allowed after discussion and in agreement with medical monitor and 
withdraw subject from study
Grade 3 

First occurrence
o
Consult ophthalmologist immediately
o
Interrupt treatment with GSK2857916
o
Once resolved to G1: Restart treatment with GSK2857916 at 25% -50%  dose 
reduction if the investigator and Medical Monitor agree that the potential benefits 
outweigh the risks

Second occurrence
o
Consult ophthalmologist immediately
Permanently discontinue treatment with GSK2857916
Grade 3/ Grade 4
Rationale for Changes: The requirement to permanently discontinue GSK2857916 
for Grade 3 ocular toxicity was revised to require study treatment to be interrupted 
and to allow for these events to be discussed with regard to type of event and the 
duration of time for the event to resolve to Grade 1 or to baseline. If study treatment 
resumes, the dose will be reduced by at least 25% of the dose that was administered 
when event occurred.
18. Section 4.1 Description of Investigation Product; Section 4.2 
The lot number indicated on the label refers to labelled lot number; the batch 
Lot#132373860 may not be provided on the label.
Before use, thaw each vial of GSK2857916 for Infusion, 20mg/mL, 1.5mL for up to 4 
hours under refrigerated conditions (2-8C), protected from light.  Following thawing, 
gently swirl the vial to ensure uniformity.  GSK2857916 should be diluted in normal 
saline (0.9%) to no more than 2 mg/mL and no less than 0.2 mg/mL. Refer to the Study 
Procedures Manual (SPM) for further details on preparation of GSK2857916.


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The dosing solution of GSK2857916 can be held under refrigerated conditions (2-8C),
for up to 24 hours (NOTE: For centers in Canada up to 8 hours only) or 4 hours at 
ambient temperature (diluted drug product in bag) from a stability perspective, but should 
be used as soon as possible as the product does not contain an antimicrobial preservative.
Rationale for Change: Clarify that lot number 132373860 refers to manufacturer batch 
lot number. 
19. Section 5.1 Number of Subjects
An adequate number of subjects will be enrolled into the study to establish the 
recommended dose(s) for further study.  It is estimated that approximately 30 subjects 
will be enrolled into Part 1, Schedule 1 (dose-escalation) of the study.  Up to 40 subjects 
with MM and up to 10 subjects with other BCMA positive hematologic malignancies
lymphomas (50 subjects total) will be enrolled in Part 2 (expansion cohort).  The 
number of subjects in the expansion cohort has been estimated based on expected 
variable expression of BCMA in those subjects (about 1/3 low, 1/3 medium, 1/3 high 
expression; approximately 13 subjects/group).  The level of BCMA expression in a given 
subject is expected to impact target-mediated clearance, which as a consequence might be 
reflected in the PK/PD variability and safety profile of individual subjects.  In addition, 
the sample size of 40 subjects in the MM cohort will allow for assessment of early signals 
of clinical activity and its relationship (if any) to variable target expression levels.  A total 
of approximately 80 subjects will be enrolled in the study.If Part 1, Schedule 2 (once 
weekly schedule) is explored, up to 15 additional subjects will be enrolled; then a total of 
approximately 95 subjects will be enrolled in the study.
Rationale for Change: The number of subjects in dose escalation is increased to allow 
for the weekly dosing schedule to be investigated as the estimated 30 subjects in dose 
escalation were allocated to the Q3week schedule. 
20. Section 5.2.1 Inclusion Criteria
2. Male or female, 18 years or older (at the time consent is obtained) and must have a 
body weight of at least 45 kg (99 lb). 
4. Part 2/Other BCMA positive Hematologic Malignancies cohort: 
d. Subject with one of the following hematologic malignancies lymphomas:
Waldenstrom’s Macroglobulinemia (WM), Diffuse Large B-cell Lymphoma 
(DLBCL), or and chronic lymphocytic leukemia (CLL) follicular lymphoma 
(FL) that exhibits positive BCMA expression on tumor cells as determined by a 
central laboratory using a validated IHC assay. The BCMA positivity is defined 
as having approximately 60% of tumor cells staining positive for BCMA, and 
the staining intensity must be 2 on IHC scale 0-3.
Eligible subjects with BCMA positive malignancies lymphomas must also fulfill the 
prior treatment requirements as follows:
e.DLBCL and WM: at least 2 prior lines of systemic therapy containing at least one 
line of chemo-immunotherapy with anti-CD20 antibody, and either has 
undergone stem cell transplant or is considered transplant ineligible.


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f.FL: at least 2 prior lines of systemic therapy CLL: at least 2 prior lines of 
systemic therapies, and who are refractory to fludarabine, and failed (or are 
ineligible) for rituximab, ofatumumab and bendamustine.
6. Adequate organ system functions as defined in Table below:
General
Ca
1.1xULN 
21. Section 5.2.2 Exclusion Criteria
1. Systemic anti-myeloma tumor therapy within 14 days, or plasmapheresis within 7 days 
prior to the first dose of study drug.
17. Subjects with positive test for hepatitis C (HCV) infection are excluded regardless of 
viral load.  If hepatitis C antibody test is positive, a confirmatory polymerase chain 
reaction (PCR) or recombinant immunoblot assay (RIBA) test should be performed.  If 
the PCR or RIBA test is negative, subject is eligible for this trial.
Rationale for Changes: removed the minimum weight in Inclusion criterion 2 as that 
was required for the lowest doses administered during dose escalation. The Part 2 
hematologic malignancies were refined to include DLBCL and FL only based on the 
frequency of BCMA expression and the intensity of expression observed. 
22. Section 7 Study Assessments and Procedures and Time and Events Tables
The maximum amount of blood collected in Screening and during the first Cycle 1 from 
each subject for the Dose Escalation and for the Dose Expansion is no more than 158 162
ml of blood (See Appendix 10).
The following changes were made to all Time and Events Tables in Section 7.1.1.2, and 
all Tables in Section 7.1.2; selected changes made to Table in Section 7.1.1.1 are 
indicated in parentheses:

End of Study visit was clarified as End of Study Treatment visit (also Section 
7.1.1.1)

Study Assessment: CK-MB (local), Troponin; BM biopsy for disease assessment 
and BCMA expression (IHC); Peripheral blood (flow for TBNK and intracellular 
cytokine testing). For Tables referring to Part 2 study assessment: PGxGenetics 
sample. For Part 2 MM cohort study assessments: e-Diary and Exit Interview and 
all associated visits.

Serum for ADA, Plasma for cfDNA, and whole blood for TBNK analysis at 
screening was moved to Day 1 cycle 1 pre-dose. 

C1 D8 visit added for whole blood for TBNK/intracellular cytokine analyses

Footnotes (note footnote number provided as the number may not be consistent 
across all tables: 
o
Screening examination to include BCVA (best-corrected visual acuity), 
slit lamp examination (with special focus on cornea), intraocular pressure, 


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dilated fundoscopic examination may be performed within 21 days prior to 
first dose. (also Section 7.1.1.1)
o
On-study exams to include BCVA (best-corrected visual acuity) and slit 
lamp examination (with special focus on cornea); window for exams is up 
to 3 days prior to dosing. (also Section 7.1.1.1)
o
Description of change: BNP and CK-MB can be measured by central or 
local lab. (also Section 7.1.1.1)
o
On days where ECG timepoints align with PK sampling timepoints, ECGs 
should be performed prior to PK samples being drawn (PK sample should 
be taken at the exact nominal time). (also Section 7.1.1.1)
o
At Screening, LVEF may be performed within 30 days prior to first dose. 
All ECHOs indicated on dosing days may be performed up to 5 days 
before dosing. All ECHOs to be done locally and sent to GSK for central 
imaging storage. (also Section 7.1.1.1)
o
Description of change for TBNK blood sample: no longer collected at 
Screening but collected C1D1 predose.
o
For Part 2 Tables: 26. Informed consent for optional PGx 
(pharmacogenetics) genetics research should be obtained before collecting 
a sample.
o
For Part 2 MM: e-Diary to be completed at screening, then Days 1-7, 8, 15 
of each treatment cycle. Upon implementation of the e-Diary, these 
assessments will be required. Exit interview to be performed within 14 
days of end of study visit.
Rationale for Changes: Ocular and ECHOs assessments window increased at 
Screening for ocular and on dosing days to allow flexibility for scheduling of 
these assessments prior to dosing. Baseline blood samples for ADA and 
biomarker tests moved to C1D1 to only collect those samples from eligible 
subjects who receive study treatment. Allow for BNP and CK-MB testing by 
central laboratory as not all site local laboratories perform these tests. 
23. Section 7.2 Baseline Assessments
Baseline (Screening) assessments obtained will include:

Imaging studies (extramedullary disease for MM if indicated,or CT/PET scan for 
other hematologic malignancieslymphomas)

For MM: BM aspirate for FISH, BCMA (flow cytometry), PD (target engagement 
and caspase 3); BCMA expression (IHC)

Serum (soluble BCMA, cytokines, and anti-drug-antibodies)

Plasma cfDNA

Peripheral blood (flow for TBNK)

For MM: BM biopsy for disease assessment and BCMA expression (IHC)

For other hematologic malignancies Lymphomas: archival or fresh tissue evaluation 
for BCMA expression
24. Section 7.3.6 Laboratory Assessments


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Table 15:
Hepatitis C (Hep C antibody -- if second generation Hepatitis C antibody positive, a hepatitis 
C antibody Chiron RIBA immunoblot assay or a validated HCV PCR viral test should be 
reflexively performed on the same sample to confirm the result)
25. Section 7.3.8 Immunogenicity 
Serum samples for determination of anti-GSK2857916 antibodies will be taken from 
all subjects in this study at the time-points specified in the Time and Events Tables in 
Section 7.1.  Timing of the assessments may be adjusted based on emerging data.  
Details of sample preparation, storage and analysis will be provided in the SPM.
Samples will be analyzed for the presence of anti-GSK2857916 antibodies by a 
validated electrochemiluminescent immunoassay. All samples will be tested in 
ascreening assay, and positive samples will be further characterized for specificity 
and antibody titers. 
Rationale for Change: Included section to describe specifics on the immunogenicity 
assessments. 
26. Section 7.5 Translation Research
Section 7.5.1: 
Whole blood count of mononuclear cells (PBMC) and their activation status and 
intracellular cytokine profile.
Section 7.5.1.4: 
Clusters of markers circulating in the plasmablood have been found to correlate with 
tumor pathway activation.  A broad panel of cytokines/chemokines will be evaluated at 
various timepoints as outlined in the Time and Events table (Section 7.1) and correlated 
with clinical outcome to treatment with GSK2857916. In addition to measuring total 
cytokine levels in serum, activated lymphocytes and monocytes producing involved in 
the cytokine production will be determined via intracellular cytokine assay. 
Section 7.5.2:
Baseline measurements of BCMA expression on tumour tissue plasma cells will be 
measured BCMA exhibits varied expression across B-cell hematological malignancies 
and therefore, BCMA expression levels at baseline may be an important predictor of 
response to GSK2857916. To evaluate whether BCMA expression has utility in patient 
stratification or selection, malignant plasma cells at baseline will be measured for BCMA 
expression by IHC and/or flow cytometry.since this may be important for potential 
retrospective stratification of subjects more likely to respond to GSK2857916.  Because 
BCMA can also be detected in circulation, the soluble form (sBCMA) has the potential to 
serve as a surrogate for cell surface BCMA marker expression. This study will correlate 


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subject’s sBCMA levels with cell surface expression and clinical response to support 
future validation of sBCMA as a patient selection marker, if data warrant.
Novel candidate biomarkers and subsequently discovered biomarkers of the biological 
response associated with advanced multiple myeloma, hematological 
malignancieslymphomas and/or medically related conditions, as well as the biological 
and clinical responses to GSK2857916 may also be evaluated.  These analyses may 
include but not be limited to:

Tumor/plasma cell BCMA receptor expression by flow cytometry and/or IHC.    

Soluble factors, including circulating cfDNA analysis of tumor tissue and plasma and 
cytokine/chemokine analysis of plasma

Additional soluble measurements to include serum levels of free sBCMA 

Activated PBMC count analysis of whole blood and intracellular cytokine assessment
27. Section 7.6 Pharmacogenetics Genetics
An important exploratory objective of the clinical study is pharmacogenetic (PGx)
genetic research.  Participation in PGx is optional but all subjects who are eligible for the 
clinical study and are enrolled into part 2 (expansion cohort) will be given the 
opportunity to participate.  Subjects may decline participation without effect on their 
medical care or care during the clinical study.  A separate consent signature is required 
for PGx genetic research.
Subjects who provide consent will have a blood sample taken for analysis.  The 
presence/absence of genetic variations in host DNA will be analyzed to determine their 
relationship with response (safety, tolerability, pharmacokinetics (PK) and efficacy) to 
treatment with GSK2857916.
Information regarding PGx research genetic research is included in Appendix 7.  In 
approving the clinical protocol the IEC/IRB and, where required, the applicable 
regulatory agency are also approving the PGx genetic research described in Appendix 7
unless otherwise indicated.  Where required by regulatory authorities, approval of the 
PGxgenetic assessments can occur after approval is obtained for the rest of the study.  If 
so, then the written approval will clearly indicate approval of the PGx genetic
assessments is being deferred and the study, except for PGxgenetic assessments, can be 
initiated.  When PGxgenetic assessments will not be approved, then the approval for the 
rest of the study will clearly.
Rationale for Change: Also allow for genetic research to include analyses of genetic 
variants with disease susceptibility, severity, and progression of disease.
28. Section 7.8 Health Outcomes:Quality of Life
Health Outcomes Endpoints


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The patient reported outcome (PRO) instruments that will be used are the Bone 
Pain/Fatigue Assessment via an e-Diary. In the Part 2 multiple myeloma cohort, the 
implementation of this assessment will occur upon availability of the instruments.
Bone Pain/Fatigue Assessment: Bone pain burden will be measured by e-Diary consisting 
of certain modified questions from Brief Pain Inventory-Short Form (BPI-SF) which 
assesses pain intensity and the interference of pain with daily life [Atkinson, 2010; 
Cleeland, 1994] and Brief Fatigue Inventory (BFI) [Cleeland, 2010]. The BPI-SF is one 
of the most frequently used pain assessments [Cleeland, 2009] and has been used in 
various disease areas, including cancer pain and neuropathic pain [Daut, 1982; McDowell 
1996]. The questionnaire has demonstrated both reliability and validity across cultures 
and languages [Cleeland, 1994]. The BFI has also been used in cancer patients to 
measure fatigue [Mendoza, 1999].
Bone pain and fatigue burden will be measured by an e-Diary consisting of 7 short 
questions, including 4 questions to assess pain intensity (severity) and one question to 
assess the interference of pain with daily life activities. The items ask about pain 
experienced within the last 24 hours. It also includes 2 questions on use of pain 
medication. Fatigue will be measured by 2 short questions – one to assess the level of 
fatigue in the past 24 hours and the second to assess the interference of fatigue with 
general activity. Data from this e-Diary will be used to understand and characterize 
pain/fatigue experience and explore time to potential pain relief while controlling for the 
use of pain medication.
It is expected that the improvement in intensity of bone pain/fatigue and the impact of 
bone pain/fatigue on general activity will take place within the first 8 cycles of treatment 
and the self-completion of the e-Diary during this period will accurately capture the 
changes in bone pain/fatigue.
Upon availability of the Bone Pain/Fatigue Assessment e-Diary, MM subjects will self-
complete the assessments at the following times:

Starting 2-4 days prior to Cycle 1 Day 1

Daily from Day 1 through Day 8 for each Cycle to time of study treatment 
discontinuation

Day 15 of each Cycle to time of study treatment discontinuation

Study Treatment Discontinuation visit
Samples of the paper versions of the PRO questionnaires are included in SPM.
29. Section 13. 7.2.3 Immunogenicity Analyses (Section 14 deleted)
For each subject, the results and titers of anti-GSK2857916 binding antibodies will be 
listed for each assessment time point.  The frequency and percentage of subjects with 
positive and negative results will be summarized for each assessment time and overall for 
each subject by dose cohort.
Rationale for Change: Section was placed in Safety Analyes sections.


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30. Section 13.7.8 Health Outcome Analyses
Symptom imact and HRQoL will be assessed using the e-Diary. Chage from baseline and 
change over time will be summarized. 
31. The calculation of scores and methods to deal with missing data will be provided in 
the RAP. Section 16.3 Appenidx 3: Response Definition after Treatment for 
Patients with CLL
Entire section deleted as CLL is no longer a hematologic malignancy under investigator 
in Part 2. 
32. Section 16.6 Appendix 7 Pharmacogenetics (PGx) Genetics
Updated with current template language which allows for analyses of genetic variants
with disease susceptibility, severity, and progression of disease.


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16.11.5.
Amendment 5
Amendment 5 applies to all sites in Canada, United Kingdom, and United States
The protocol Amendment 4 dated 05 May 2016 (applied to all sites) is replaced by 
Amendment 5 with the effective date of DD MMM YYYY.
Summary of Changes
The following protocol changes have been implemented to include additional follow up 
of multiple myeloma subjects for ocular exams (for those whose corneal signs or 
symptoms have not resolved), additional patient reported outcome instruments, addition 
of time-to-event endpoints as exploratory objectives. Subjects who have completed 
treatment or the 3 month follow up visit (end of study) prior to amendment 5 will be 
reconsented for further follow up and survival status. Other administrative changes are 
also included
Original text displayed as strikethrough indicates replaced or removed text. New text is 
displayed as underline. Revisions within tables is either presented with the entire table or 
displayed as text (i.e., for larger tables). Typos or minor word changes are not presented.
List of Changes
1.
List of Abbreviations
CI
Confidence interval
DOR
Duration of response
NEI-VFQ-25
National Eye Institute Visual Functioning Questionnaire - 25
OSDI
Ocular Surface Disease Index
PFS
Progression-free survival
SD
Stable disease
TTP
Time to progression
Rationale for Change: Updated to include new abbreviations used within the 
amendment.


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2.
Protocol Synopsis
STUDY OBJECTIVES, ENDPOINTS AND HYPOTHESES
Objective
Endpoint
Exploratory

To explore the effect of GSK2857916 on bone 
pain symptoms (including bone pain, fatigue 
and visual symptoms) and impacts on and 
HRQoL in subjects with relapsed/refractory 
MM (Part 2)

Changes from baseline in bone pain/fatigue 
and analgesic use as measured by the eDiary

Interviews with subjects to further characterize 
changes in bone pain symptoms (including 
bone pain, fatigue and visual symptoms) and 
impacts on HRQoL

To explore changes in visual symptoms and 
function following discontinuation of treatment 
with GSK2857916

Changes in visual symptoms and impacts as 
measured by the OSDI and NEI-VFQ-25 
following treatment discontinuation

Follow-up telephone interviews conducted to 
further understand subjects experience with 
visual symptoms and changes in symptoms 
and related impacts following treatment 
discontinuation

To explore the initial anti-tumor activity of 
GSK2857916 in subjects with 
relapsed/refractory MM in terms of time-to-
event (TTE) endpoints (Part 2 MM)

Time to progression (TTP), defined as: the 
time from first dose until the earliest date of 
PD per International Multiple Myeloma 
Working Group (IMWG), or death due to PD.

Duration of response (DOR), defined as: the 
time from first documented evidence of PR or 
better; until the time when disease progression 
(PD) is documented per IMWG; or death due 
to PD occurs in participants who achieve a 
response, i.e. confirmed PR or better.

Time to response (TTR), defined as: the time 
between the date of first dose and the first 
documented evidence of response (PR or 
better).

Progression-free survival (PFS), defined as: the 
time from first dose until the earliest date of 
disease progression (PD) per IMWG, or death 
due to any cause.
Rationale for Change: To align with changes made in the main Objectives and 
Endpoints table.
PATIENT REPORTED OUTCOMES
Part 2/MM cohort: changes in symptoms and health-related quality of life (HRQoL) will 
be assessed with the use of the Bone Pain/Fatigue diary.
Changes in visual symptoms and impacts with the use of the OSDI and NEI-VFQ-25


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Rationale for Change: Questionnaires added to obtain additional patient information on 
the resolution of corneal events after the treatment period.
STATISTICAL METHODS
Part1: After each dosing cohort, the N-CRM will be used to recommend the next dose 
level based on observed dose-limiting toxicities (DLTs).  The dose escalation decisions 
will be based on this recommendation as well as the totality of the safety, 
pharmacokinetic, and pharmacodynamic data.
Part 2: Futility analyses will be performed on the MM cohort after approximately 15, 22, 
and 30 evaluable subjects have been enrolled. The methodology utilized is based on the 
predictive probability of success if enrollment continues to 40 subjects [Lee, 2008].
Clinical Activity
The exact 95% confidence interval (CI) for overall response rate (ORR) and clinical 
benefit rate (CBR) will be provided. Subjects with unknown or missing response will be 
treated as non-responders, i.e., these subjects will be included in the denominator when 
calculating percentages of response.
For the Part 2 MM population, additional exploratory time-to-event (TTE) endpoint will 
include TTP, DOR, TTR, and PFS, as data permits. For all the TTE endpoints listed 
above, median TTE with 95% CI will be estimated employing the Kaplan-Meier method 
as data permits. A Kaplan-Meier survival curve will be generated. The number and 
percentage of subjects who had the event or were censored will also be reported.
Adverse Events: Adverse events will be summarized by frequency and proportion of 
total participants, by system organ class and preferred term. Separate summaries will be 
given for all AEs, treatment-related AEs, SAEs, and AEs leading to discontinuation of 
study treatment.
The incidence of deaths and the primary cause of death will be summarized.
Clinical Laboratory Evaluation: The evaluation of clinical laboratory tests will focus 
on selected laboratory analytes from the hematology and blood chemistry panel.
Descriptive statistics (mean, standard deviation, median, range) will be used to 
summarize observed laboratory values and change from baseline in observed value at 
each scheduled visit or worst-case post baseline, as appropriate.
The worst-case- toxicity grade in hematology and chemistry result during the treatment 
will be summarized. Shift tables from baseline to the worst toxicity grade during 
treatment will be provided for each laboratory analyte.
Other Safety Measures: Data for vital signs, electrocardiograms (ECGs), and 
echocardiograms (ECHOs) will be summarized. For continuous variables, these 
summaries will include sample size, mean, median, standard deviation, minimum, and 


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maximum.  For categorical variables, the summaries will include frequencies and 
corresponding percentages.  
Rationale for Change: To further clarify and define statistical analyses.
3.
Section 2.0
Objective(S), Endpoint(S) And Hypothesis
Objective
Endpoint
Exploratory

To explore the effect of GSK2857916 on bone 
pain/fatiguesymptoms (including bone pain, 
fatigue and visual symptoms) and impacts on
and HRQoL in subjects with relapsed/refractory 
MM (Part 2)

Changes from baseline in bone pain/fatigue 
and analgesic use as measured by the eDiary

Interviews with subjects to further characterize 
changes in bone pain symptoms (including 
bone pain, fatigue and visual symptoms) and 
impacts on HRQoL

To explore changes in visual symptoms and 
function following discontinuation of treatment 
with GSK2857916 (Part 2 MM)

Changes in visual symptoms and impacts as 
measured by the OSDI and NEI-VFQ-25 
following treatment discontinuation

Follow-up telephone interviews conducted to 
further understand subjects experience with 
visual symptoms and changes in symptoms 
and related impacts following treatment 
discontinuation

To explore the initial anti-tumor activity of 
GSK2857916 in subjects with 
relapsed/refractory MM in terms of time-to-
event (TTE) endpoints (Part 2 MM)

Time to progression (TTP), defined as: the 
time from first dose until the earliest date of 
PD per International Multiple Myeloma 
Working Group (IMWG), or death due to PD.

Duration of response (DOR), defined as: the 
time from first documented evidence of PR or 
better; until the time when disease progression 
(PD) is documented per IMWG; or death due 
to PD occurs in subjects who achieve a 
response, i.e. confirmed PR or better.

Time to response (TTR), defined as: the time 
between the date of first dose and the first 
documented evidence of response (PR or 
better).

Progression-free survival (PFS), defined as: the 
time from first dose until the earliest date of 
disease progression (PD) per IMWG, or death 
due to any cause.
Rationale for Change: To further define and clarify the objectives of the QoL 
questionnaire and interviews; to implement follow up questionnaires for patients 
experiencing ocular symptoms post dosing; to further define and clarify statistical 
endpoints.


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4.
Section 5.2.1.
Inclusion Criteria
Table 14
Adequate Organ System Function
System
Laboratory Values
Total bilirubin
≤1.525 X ULN (isolated bilirubin ><1.5xULN is 
acceptable if bilirubin is fractionated and direct 
bilirubin <35%)
Rationale for Change: Clarification as per Note to file submitted to all sites.
5.
Section 6.2 
Subject Completion Criteria
For Part 1 (dose-escalation phase), a completed subject is one who has completed at least 
1 cycle of study treatment and an End of Study Visit without events causing them to 
withdraw or discontinue from the study for reasons listed  in Section 6.3  For Part 2 
(expansion cohort), a completed subject is one who has received at least one dose of 
study treatment without events causing them to withdraw or discontinue study treatment 
for reasons listed in Section 6.3 and completed an End of Study Visit.
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 before the end of the study, has not 
been lost to follow-up, or has not withdrawn consent from study participation.
Rationale for Change: To clarify subject study completion criteria.


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6.
Section 7.1.2.1. Every 3 Weeks Dosing Schedule for Multiple Myeloma
Time and Events Table for Full Study (Cycle = 21 days)
Study 
Assessments1
Screen2
Day 
1 
C1
Day 
8 
C1
Day 
15 
C1
Day 1 
C2
D1 of C3-C16
End of 
Study 
Treatment34
Monthly 
Follow 
up35
3-
Month 
Off-
study 
Follow-
up
Ocular Exam
X3
X4
At the start of 
each cycle4
X4
X35
Pregnancy 
Test
X10
At the start of 
cycles 510, 910, 
1310
X10
X11
X11
OSDI
X31
X31
NEI-VFQ-2531
X31
X31
Exit Interview
X3132
Follow-up 
Interview
X33
Survival Status
X29
X29
Subsequent 
Treatment
X29
X29
4.
On-study exams, to include BCVA (best-corrected visual acuity) and slit lamp examination (with special focus on 
cornea); window for exams is up to 3 days prior to dosing. In the event that a subject has a dose delay due to a non-
ocular toxicity and an ocular exam has been performed for that cycle, a repeat ocular exam 3 days prior to dosing may 
be omitted if the participant did not have corneal signs on the previous exam and does not have any new corneal 
symptoms.
5.
On initial (first infusion) dosing day, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +10 
minutes, +30 minutes (515 min) after SOI, EOI, and 1 hour post EOI.  On subsequent dosing days, vital signs must 
be assessed at pre-dose (within 30 minutes prior to SOI), +30 minutes after SOI, and EOI.  On days where vital sign 
timepoints align with PK sampling timepoints, vital signs should be assessed prior to PK samples being 
drawn.
29. All participants should be followed for survival for 1 year from last subject last dose. Record subject’s survival 
status and whether subsequent treatment for disease was given.  Subject does not need to come in for visit.
Participants who have completed treatment or the 3 month follow up visit (end of study) prior to amendment 5 will be 
reconsented for further follow up and survival status.
31. OSDI and NEI-VFQ-25 to be administered during end of study treatment visit.  Additional assessments for subjects 
who are experiencing corneal symptoms to be completed via telephone on a monthly basis for up to 1 year, or until 
resolution of symptoms (whichever comes first) during the follow-up period. 
32. Exit interview to be performed within 14 21 days of end of study visit
33. Optional follow-up telephone interview interview to explore visual symptoms and changes in symptoms and related 
impacts following treatment discontinuation be performed at least 6 months following the End of Study Treatment visit.  
This interview would only be for those subjects who experienced corneal symptoms during treatment and consent to 
participate.
34. End of treatment visit should be performed within 30 days (+7 days) after the last dose or prior to the start of new 
anti-cancer treatment, whichever is earlier. In cases where more than 30 days (+7 days) have elapsed from the date of 
the subject’s last dose due to dosing delays and a subsequent decision to take the subject off treatment, the end of 
study treatment visit should be scheduled as soon as possible to allow the final assessments to be performed at the 
earliest date.
35. Participants with corneal signs or symptoms at the end of study treatment visit should be monitored by ophthalmic 
exam once a every month after the last study dose until deemed clinically stable by an eye care professional complete 
resolution or for 12 months (whichever comes first). Corneal exams to include BCVA and slit lamp examination (with 


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special focus on cornea). Participants who have completed treatment or the 3 month follow up visit (end of study) will 
be reconsented for further additional ophthalmology follow up.
36. The 3-month off study follow up visit should be performed within 3 months (90 days) (±7 days) after the last dose. 
The subject is not required to come to the clinic for this visit (except when a pregnancy test is required). The 
assessments can be performed by phone calls, email or other means of communication.
Rationale for Change: To implement monthly follow ups and clarify administrative 
inconsistencies in the Time and Events Table.   Increase the window for performing the 
Exit Interview in order to allow additional flexibility in scheduling.
7.
Section 7.1.2.3. Dose Expansion Every 3 Weeks Dosing Schedule for 
Lymphomas
Study 
Assessments1
Screen2
Day 
1 
C1
Day 
8 C1
Day 
15 
C1
Day 1 
C2
D1 of C3-C16
End of 
Study 
Treatment26
Monthly 
Follow 
up27
3-
Month 
Off-
study 
Follow-
up
Ocular Exam
X3
X4
At the start of 
each cycle4
X4
X27
Pregnancy 
Test 
X10
At the start of 
cycles 510, 910, 
1310
X10
X11
X11
Survival Status
X25
X25
Subsequent 
Treatment
X25
X25
4.
On-study exams to include BCVA (best-corrected visual acuity) and slit lamp examination (with special focus on 
cornea); window for exams is up to 3 days prior to dosing.  In the event that a subject has a dose delay due to a non-
ocular toxicity and an ocular exam has been performed for that cycle, a repeat ocular exam 3 days prior to dosing may 
be omitted if the participant did not have corneal signs on the previous exam and does not have any new corneal 
symptoms. investigator determines that it is not medically necessary and the subject does not have any new ocular 
symptoms. 
5.
On initial (first infusion) dosing day, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +10 
minutes, +30 minutes (± 515 min) after SOI, EOI, and 1 hour post EOI.  On subsequent dosing days, vital signs must 
be assessed at pre-dose (within 30 minutes prior to SOI), +30 minutes after SOI, and EOI.  On days where vital sign 
timepoints align with PK sampling timepoints, vital signs should be assessed prior to PK samples being 
drawn.  
21.
CT/PET or CT scans from within 21 days prior to first dose are acceptable. CT scans are acceptable at all 
restaging assessments unless CR is suspected, in which case a PET/CT scan will be obtained to confirm CR.
25. Record subject’s survival status until last subject completes or discontinues treatment and whether subsequent 
treatment for disease was given.  Subject does not need to come in for visit.
26. End of treatment visit should be performed within 30 days (+7 days) after the last dose or prior to the start of new 
anti-cancer treatment, whichever is earlier. In cases where more than 30 days (+7 days) have elapsed from the date of 
the subject’s last dose due to dosing delays and a subsequent decision to take the subject off treatment, the end of 
study treatment visit should be scheduled as soon as possible to allow the final assessments to be performed at the 
earliest date.
27. All participants should be followed for survival for 1 year from last dose. Participants with corneal signs or 
symptoms at the end of study treatment visit should be monitored by ophthalmic exam every month after the last study 


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dose until deemed clinically stable by an eye care professional or for 12 months (whichever comes first). Corneal 
exams to include BCVA and slit lamp examination (with special focus on cornea).
Rationale for Change: To align with additional follow ups implemented in the MM 
cohort.
8.
Section 7.1.2.4. Dose Expansion Weekly Dosing Schedule for Lymphomas
4. On-study exams, to include BCVA (best-corrected visual acuity) and slit lamp examination (with special focus on 
cornea); window for exams is up to 3 days prior to dosing. In the event that a subject has a dose delay due to a non-
ocular toxicity and an ocular exam has been performed for that cycle, a repeat ocular exam 3 days prior to dosing may 
be omitted if the participant did not have corneal signs on the previous exam and does not have any new corneal 
symptoms.
Rationale for Change: To clarify that ocular exams do not need to occur if already 
completed in that cycle if there are no corneal signs and symptoms after the treatment 
period.


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9.
Section 7.3
Safety Evaluations
Section 7.3.6. Ocular Exam
An ocular exam to include BCVA (best-corrected visual acquity), slit lamp examination 
(with special focus on the cornea), intraocular pressure, and dilated funduscopic 
examination will be conducted for all subjects at screening. Additional exams will be 
performed as specified in the Time and Events Tables (Section 7.1) during the treatment 
period and at monthly follow-up visits as clinically indicated. 
Rationale for Change: To add further follow up visits to assess corneal signs and 
symptoms after the treatment period.
Section 7.3.10. Visual Functioning Questionnaires
The impact of potential ocular toxicity on function and health-related quality of life will 
be assessed with the use of 2 visual function questionnaires: the National Eye Institute 
Visual Functioning Questionnaire-25 (NEI VFQ-25), and the Ocular Surface Disease 
Index (OSDI).  Subjects will complete the self-administered versions of these two 
assessments during their End of Study Treatment visit.  Subjects who are unable to 
complete the questionnaire on their own due to blurry vision, and require assistance can 
have the questionnaire read to them by an interviewer.  If the questionnaires are 
administrated by an Interviewer, then the questionnaire should be read to the subjects 
verbatim, and subject responses should be recorded directly without any interpretation.  
Subjects who continue to experience visual symptoms after discontinuation of study 
treatment will complete additional interviewer-administered assessments via telephone on 
a monthly basis for up to 1 year during the Follow-up period or until the resolution of 
their visual symptoms, whichever comes first.
Section 7.3.10. 1. National Eye Institute Visual Functioning Questionnaire-25
The NEI-VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 
vision-related constructs, plus an additional single-item general health rating question 
[Mangione., 2001].  The NEIVFQ-25 generates the following vision-targeted sub-scales:  
global vision rating difficulty with near vision activities; difficulty with distance vision 
activities; limitations in social functioning due to vision; role limitations due to vision; 
dependency on others due to vision; mental health symptoms due to vision; driving 
difficulties; limitations with peripheral vision, limitations with color vision; and corneal 
pain.  In addition to the core items from the NEI-VFQ-25, select questions from the 
Appendix of Optional Additional Questions will be administered to further assess the 
impact of corneal events on visual function.  
Section 7.3.10. 2. Ocular Surface Disease Index Questionnaire
The Ocular Surface Disease Index (OSDI) is a 12-item questionnaire designed to assess 
both the frequency of dry eye symptoms and their impact on vision-related functioning 
[Schiffman, 2000]. The OSDI has demonstrated good reliability, validity, sensitivity, and 
specificity, and can be used as a complement to other clinical and subjective measures of 
dry eye disease by providing a quantifiable assessment of dry eye symptom frequency 
and the impact of these symptoms on vision-related functioning.


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Rationale for Change: To implement questionnaires at the end of study treatment visit 
and during follow-up for patients experiencing ocular symptoms, in order to assess 
changes in visual symptoms and function following discontinuation of treatment with 
GSK2857916.
10. Section 7.8. Health Outcomes: Quality of Life
Health Outcomes EndpointsSection 7.8.1. Bone Pain/Fatigue Assessment (eDiary)
Section 7.8.2. Exit Interview and Follow-up Interview
To further evaluate disease and treatment related symptoms (including bone pain and 
fatigue, and visual symptoms) and associated impacts on function and health-related 
quality-of-life, participants in the Part 2 multiple myeloma cohort will complete an 
optional Exit Interview conducted via telephone.  The interview will be conducted by a 
trained interviewer and will be audio recorded for transcription and analysis.  The 
telephone interview should be conducted within 21 days following completion of the End 
of Study Treatment visit.
Subjects who have experienced ocular symptoms during the treatment period will have 
the option to also consent to participate in an optional Follow-up interview.  The Follow-
up interview will be conducted by a trained interview via telephone at least 6 months 
following the End of Study Treatment visit.  The Follow-up interview will focus on 
visual symptoms experienced by the subject, impacts on function and health-related 
quality-of-life and management and resolution of their visual symptoms following 
discontinuation of study treatment.
Both the Exit Interview and Follow-Up interview are optional, and the failure to complete 
either interview will not constitute a protocol deviation.
Rationale for Change: To implement follow up interviews for patients who experienced 
corneal symptoms to further understand changes in visual symptoms and function 
experienced during the study and following discontinuation of treatment with 
GSK2857916.
11.
Section 13.4.1 Analysis Populations
The ‘All Treated’ population is defined as all eligible subjects who receive at least 1dose 
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. 
Subjects 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 or 28 days for once weekly schedule) for reasons other than toxicity may be 
presented in separate tables/listings.
The ‘All Treated’ population will further be classified in the following sub-populations.


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o
Part 1: all Part 1 subjects of All Treated population. Note, subjects in Part 1 are 
exclusively multiple myeloma patients. 
o
Part 2 MM: all Part 2 MM subjects of All Treated population 
o
All Treated MM: comprise of subjects in Part 1 and Part 2 MM.
o
Part 2 NHL: all Part 2 lymphoma subjects of All Treated population.
The ‘DLT Evaluable’ population in Part 1 enables an appropriate evaluation of study 
DLTs. It is defined as those subjects fulfilling the ‘All Treated’ population criteria, and 
having met the following adequate exposure criteria: 
o
For Schedule 1 (once every 3 weeks dosing) subjects received a complete infusion 
in cycle 1. 
o
For Schedule 2 (once weekly dosing for 3 consecutive weeks, 1 week rest) 
subjects receive three infusions, two of which must be complete infusions, in 
cycle 1. (as increases up to ≤30% are implemented between cohorts, less than 2 
complete infusions would result in a total dose closer to the previous dose 
investigated).
Any subject in the “All Treated” population who experiences a DLT, as defined in 
Section 3.3.3 will also be included in the DLT evaluable population regardless of 
exposure.
The ‘PK’‘All Evaluable (MM)’ population is a subset of the ‘All Treated’ population, 
who were initially treated at RP2D in the expansion cohort and have at least two post-
baseline disease assessments or they have progressed or died or permanently 
discontinued treatment. This population will be used for the futility analysis of the MM 
expansion cohort.
The ‘Pharmacokinetic (PK) Population’ is defined as those subjects in the “All 
Treated” population from whom at least one PK sample was obtained, analyzed, and was 
measurable. 
The ‘Pharmacodynamic (PD) Population’ is defined as those subjects in the “All 
Treated” population from whom at least one PD sample was obtained, analyzed, and was 
measurable.
Rationale for Change: To further clarify and define statistical populations.
12.
Section 13.6 Interim Analysis, Section 13.6.2 Part 2
Subjects will not be replaced when they discontinue the study due to: Progression 
(symptomatic or otherwise), toxicity related to GSK2857916, or lack of efficacy.
Other administrative interim analyses may be performed if needed.


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Final analysis of MM population may be performed separately, before the NHL cohort 
completes the study. 
Rationale for Change: To further define timeframe for MM population in relation to 
NHL cohort.
13.
Section 13.7.2.2 Adverse Events
Characteristics (e.g. number of occurrences, action taken, grade, etc) of the following 
AEs of special clinical interest will be summarized separately: corneal events, 
hematologic toxicities (including but not limited to thrombocytopenia and neutropenia), 
infusion related reaction etc. Details will be provided in the RAP.
The incidence of deaths and the primary cause of death will be summarized.
Rationale for Change: To further define AEs of clinical interest.
14.
Section 13.7.2.3 Clinical Laboratory Evaluations
Hematology and clinical chemistry data will be summarized using frequencies and 
proportions according to National Cancer Institute-Common Toxicity Criteria for 
Adverse Events (NCI-CTCAE) (Version 4.0).  The evaluation of clinical laboratory tests 
will focus on selected laboratory analytes from the hematology and blood chemistry 
panel.Laboratory test results outside the reference ranges that do not have associated 
NCI-CTCAE criteria will be summarized using proportions. 
Descriptive statistics (mean, standard deviation, median, range) will be used to 
summarize observed laboratory values and change from baseline in observed value at 
each scheduled visit or worst-case post baseline, as appropriate.
The worst-case- toxicity grade in hematology and chemistry result during the treatment 
will be summarized. Shift tables from baseline to the worst toxicity grade during 
treatment will be provided for each laboratory analyte.
Further details will be provided in the Reporting and Analysis Plan (RAP).
Rationale for Change: To further define analysis of clinical laboratory evaluations.
15.
Section 13.7.2.5 Other Safety Measures
Data for vital signs, electrocardiograms (ECGs), and echocardiograms (ECHOs) will be 
summarized 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 Reporting and Analysis Plan (RAP).


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Rationale for Change: To further define analysis of ECGs and ECHOs. 
16.
Section 13.7.7 Clinical Activity Analyses
Clinical activity will be calculated based on Overall Response Rate (ORR), which is 
defined as the percentage of subjects with confirmed stringent complete response (sCR), 
complete response (CR), very good partial response (VGPR), and partial response (PR) 
as assessed by 2011 recommendation of the International Myeloma Working Group 
(IMWG) Panel I (Appendix 1).  Clinical benefit rate may be considered in addition to 
ORR.
Overall Response Rate (ORR) is one of the secondary endpoints to measure clinical 
activity of this study.  
For multiple myeloma, ORR is defined as the percentage of subjects with a confirmed PR 
or better (i.e. PR, VGPR, CR and sCR), according to the IMWG Panel I (Appendix 1), as 
assessed by the investigator. In addition, Clinical Benefit rate (CBR) is defined as the 
percentage of subjects with a confirmed MR or better (i.e.MR, PR, VGPR, CR and sCR), 
according to the IMWG Panel I (Appendix 1), as assessed by the investigator.
The number and percentage of subjects in the following response categories will be 
presented sCR (stringent complete response), (complete response) CR, (very good partial 
response) VGPR, (partial response) PR, (minimal response) MR, stable disease (SD), 
progressive disease (PD), and not evaluable (NE)
sCR+CR+VGPR+PR for overall response (ORR)
sCR+CR+VGPR+PR+MR for Clinical Benefit rate (CBR)
The corresponding exact 95% CI for ORR and Clinical Benefit Rate (CBR) will also be 
provided.  Subjects with unknown or missing response will be treated as non-responders, 
i.e., these subjects will be included in the denominator when calculating percentages of 
response.
For lymphomas, ORR is Clinical activity for lymphomas will be calculated based on 
ORR defined as the percentage of subjects with confirmed CR, or PR, as described in the 
Revised Response Criteria for Malignant Lymphoma (Appendix 2). ORR for lymphomas 
will be summarized in a similar way as multiple myeloma. The corresponding exact 95% 
CI for ORR will also be provided.
Other exploratory time-to-event (TTE) endpoints related to clinical activity for Part 2 
(MM) of this study are TTP, DOR, TTR, and PFS.
Time to disease progression (TTP) is defined as the time from first dose until the 
earliest date of PD per IMWG, or death due to PD. Determination of dates of TTP event 
and dates for censoring will be described in the RAP. Duration of response (DOR) is 
defined as the time from first documented evidence of PR or better until disease 
progression (PD) per IMWG, or death due to PD among subjects who achieve a response 


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(i.e. confirmed PR or better). Responders without disease progression will be censored at 
the censoring time point for TTP. 
Time to response (TTR) is defined as the time between the date of first dose and the 
first documented evidence of response (PR or better). Subjects without confirmed 
response (PR or better) will be censored at the censoring date for TTP. 
Progression-free survival (PFS) is defined as the time from first dose until the earliest 
date of disease progression (PD) per IMWG, or death due to any cause. Determination of 
dates of PFS event and dates for censoring will be described in the RAP. 
For all the TTE endpoints described above, median TTE with 95% CI will be estimated 
employing the Kaplan-Meier method as data permits. A Kaplan-Meier survival curve will 
be generated. The number and percentage of subjects who had the event or were censored 
will also be reported.
Exploratory subgroup analyses may be performed for all endpoints to measure clinical 
activity as appropriate.
Overall Survival: The protocol is amended to collect long-term survival data (i.e. up to 1 
year after last subject completes or discontinues treatment). Subjects who are already 
completed the study will be contacted to request re-consent.
If all the patients (who were alive at the time of study completion) can be re-consented, 
OS landmark analysis may be performed at 9 and 12 months using Kaplan-Meier analysis 
as data permits.
Otherwise, only descriptive analysis (number and % of deaths and lost to follow-up) will 
be performed.
Rationale for Change: To further define efficacy analysis and add analysis of time-to-
event endpoints. 
17.
Section 13.7.8. Health Outcome Analyses
Symptom impact and HRQoL will be assessed using the e-Diary. Change from baseline 
and change over time will be summarized. 
The calculation of scores and methods to deal with missing data will be provided in the 
RAP.
Visual Functioning Questionnaire (NEI VFQ-25 and OSDI): Data will be collected from 
end of treatment (EOT) visit as baseline. Additional data will be collected in follow-up 
visits on a monthly basis for subjects with ongoing corneal events or signs at EOT for 1 
year or until resolution, whichever occurs first. These data will not be collected for 
subjects who already completed the treatment. Calculation of scores will be provided in 
the RAP. Due to limited number of on-treatment subjects at the time of protocol 
amendment, only a listing by subject will be generated.
Rationale for Change:   To further clarify how the NEI-VFQ-25 and OSDI will be 
reported.


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18.
Section 15. References
Mangione, C. M., P. P. Lee, P. R. Gutierrez, K. Spritzer, S. Berry, R. D. Hays and I. 
National Eye Institute Visual Function Questionnaire Field Test. "Development of the 
25-item National Eye Institute Visual Function Questionnaire." Arch Ophthalmol 2001; 
119(7): 1050-1058.
Schiffman, R. M., M. D. Christianson, G. Jacobsen, J. D. Hirsch and B. L. Reis. 
"Reliability and validity of the Ocular Surface Disease Index." Arch Ophthalmol 2000; 
118(5): 615-621.
Rationale for Change: References added to align with updates to questionnaires.