Clinical trial NCT01868022
Conditions: Neoplasms
Keywords: FGFR1 FP1039 GSK3052230 docetaxel FGFR carboplatin HGS1036 squamous non-small cell lung cancer paclitaxel
Sponsor: GlaxoSmithKline
Start date: 2013-10-09; Completion date: 2017-10-24
Enrollment: 65 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This phase IB trial aims to identify anticancer activity of GSK3052230 in subjects with malignancies with abnormal dependence on FGF pathway signaling. Combination doses of GSK3052230 with standard of care chemotherapy in the first and second line or greater setting of metastatic squamous non-small cell lung cancer (NSCLC) and first line malignant pleural mesothelioma subjects will be studied in the 3+3 dose-escalation design. This will be a multi-arm, multicenter, non-randomized, parallel-group, uncontrolled, open-label Phase IB study designed to evaluate the safety, tolerability and preliminary activity of GSK3052230 in combination with paclitaxel + carboplatin (Arm A), in combination with docetaxel (Arm B), or in combination with pemetrexed + cisplatin (Arm C). Approximately 70 subjects will be enrolled in the study (approximately up to 120 may be enrolled).

Detailed description:

Arms: arm 1: Subject will receive GSK3052230 as 30-minute intravenous (i.v.) infusion once a week (Day 1, Day 8, Day 15) of each 21-day cycle + paclitaxel (constant infusion for 3 hrs) and carboplatin (constant infusion for 30 to 60 minutes) iv on Day 1 of each 21-day cycle. The number of cycles of paclitaxel/carboplatin will be limited to 4 to 6 cycles. arm 2: Subject will receive GSK3052230 as 30-minute intravenous (i.v.) infusion once a week (Day 1, Day 8, Day 15) of each 21-day cycle + docetaxel as 1 hour iv infusion on Day 1 of each 21-day cycle. Subjects may continue to receive docetaxel until disease progression or as long as they are considered to derive benefit from treatment. arm 3: Subject will receive GSK3052230 as 30 minute iv infusion once a week (Day 1, Day 8, Day 15) of each 21 day cycle + pemetrexed iv infusion over 10 minutes on Day 1 of each 21 day cycle followed 30 minutes later by iv Cisplatin infused over 2 hours
Interventions: intervention 1: GSK3052230 intervention 2: paclitaxel intervention 3: carboplatin intervention 4: docetaxel intervention 5: pemetrexed intervention 6: cisplatin
Intervention descriptions: intervention 1: A clear to opalescent, colorless to pale yellow solution for IV infusion once weekly (Day 1, Day 8, Day 15) in each 21-day cycle with unit dose strengths/dose level of 5, 10, 15, and 20 mg/kg supplied in a sterile 25 mL glass vial. intervention 2: paclitaxel will be from commercial stock. intervention 3: carboplatin will be from commercial stock. intervention 4: docetaxel will be from commercial stock. intervention 5: pemetrexed will be from commercial stock intervention 6: cisplatin will be from commercial stock

Protocol documents:
Prot_000.pdf: 
2013N165256_06
CONFIDENTIAL
The GlaxoSmithKline group of companies
FGF117360
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TITLE PAGE
Division: Worldwide Development
Retention Category: GRS019
Information Type: Protocol Amendment
Title:
Multi-arm, Non-randomized, Open-Label Phase IB Study to 
Evaluate GSK3052230 in Combination with Paclitaxel and 
Carboplatin, or Docetaxel or as Single Agent in Subjects with 
Solid Malignancies and Deregulated FGF Pathway Signaling
Compound Number:
GSK3052230
Effective Date:
14-DEC-2015
Protocol Amendment Number:  05
Subject: squamous non-small cell lung cancer, FGFR, GSK3052230, HGS1036, FP1039, 
paclitaxel, carboplatin, docetaxel, FGFR1, FGF2, permetrexed, cisplatin
Author:
Oncology Clinical Development, USA
Precision Medicine and Diagnostics, Oncology, USA
Quantitative Sciences-Oncology, USA
Biotransformation and Drug Disposition, PTS, USA
Global Clinical Safety and Pharmacovigilance, USA
Cancer Research, USA
Clinical Pharmacology Modeling & Simulation, USA
Quantitative Sciences-Genetics, USA
Clinical Immunology, USA
GMP Operations Biopharm R&D, USA
Oncology Clinical Development, USA
Copyright 2015 the GlaxoSmithKline group of companies.  All rights reserved.  
Unauthorised copying or use of this information is prohibited
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Revision Chronology
GlaxoSmithKline
Document Number
Date
Version
2013N165256_00
2013-APR-16
Original
2013N165256_01
2013-OCT-17
Amendment No. 1
This amendment is a country-specific amendment for the UK. Stopping criteria based on 
QTc interval and contraceptive requirements have been revised.
2013N165256_02
2013-NOV-07
Amendment No. 2
Amendment No.2: This amendment applies to all sites. Sponsor medical monitor 
information was updated, the inclusion criterion for FGFR gene amplification was 
modified, clarifications were made to the Time and Events Table, vital sign 
measurements, and permitted concomitant medications; and contraceptive requirements 
were corrected.
2013N165256_03
2014-FEB-03
Amendment No. 3
Amendment No.3: This amendment changed Arm C of the protocol from GSK3052230 
monotherapy of subjects with solid tumors to combination chemotherapy (GSK3052230 
plus pemetrexed and cisplatin) of subjects with mesothelioma. Associated additions to 
the protocol include safety precautions for pemetrexed and cisplatin, use of modified 
RECIST for evaluation of clinical response, assessment of forced vital capacity. Patient 
reported outcomes using the Lung Cancer Symptom Scale (LCSS) was added for 
subjects with lung cancer and LCSS-meso for subjects with mesothelioma. Additional 
background and rationale were added. Stopping rules and sample size were modified. 
Translational research objectives were clarified
2013N165256_04
2014-FEB-03
Amendment No. 3
Amendment No.3 version 2: A minor correction to Amendment 3 was made on Page 24 
to correct ototoxicity monitoring for consistency with the changes listed on page 114. As 
Amendment 3 was published prior to discovery of this inconsistency, the correction 
increases the document number from 03 to 04.
2013N165256_05
2014-OCT-15
Amendment No. 4
Amendment No.4: The protocol medical monitor contact information was updated and 
information will be provided during the study to prevent protocol amendments if there 
are staff changes.  Additional information on preclinical studies in mesothelioma was 
added in the background section, and clarifications were provided for modified RECIST, 
the time & event tables, concomitant medications and Cockcroft-gault formula 
description.  In Arm B, the criteria for entry has been broaden to greater than two prior 
lines of therapy.  The protocol was expanded to allow intra-subject dose escalation or de-
escalation.  This allows subjects who receive benefit during the dose escalation to 
transition to the recommended expansion dose.  In addition, additional wording has been 
added to allow alternative dosing and schedules to be explored.  


2013N165256_06
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FGF117360
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2013N165256_06
2015-DEC-14
Amendment No. 5
Amendment No.5: Changes including (1) the medical monitors contacts, (2) synopsis 
wording clarified to be consistent with the changes in Amendment 4 regarding confirmed 
diagnosis being Stage IIIB or IV for subjects in Arm A or B; (3) provide additional 
wording that chemotherapy such as cisplatin should be administered per local standards, 
(4) providing additional guidance for GSK3052230 dosing with extended infusion 
timings and pre-medication per local institutional standard practice, (5) providing more 
flexible timing for subjects in Arm A screening who desire to start chemotherapy prior to 
GSK3052230 first dose, (6) providing new PK sampling for cisplatin for Arm C subjects, 
and (7) requiring total calcium instead of total calcium and ionized calcium at selected 
sites in the UK.


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MEDICAL MONITOR INFORMATION PAGE
Medical Monitor and Sponsor Contact Information:
Role
Name
Day Time 
Phone 
Number
After-hours 
Phone/Cell/
Pager 
Number
Fax 
Number
GSK Address
Medical 
Monitor
 
MD, PhD
GlaxoSmithKline
1250 South Collegeville Road
PO Box 5089
Collegeville, PA 19426-0989, 
United States
Email: 
Secondary 
Medical 
Monitor
 MD
GlaxoSmithKline
1250 S. Collegeville Road, 
Collegeville, PA 19426-0989, 
United States
Email:  
Additional medical monitor or sponsor contacts may be provided in a letter to investigator during the course 
of the study conduct without involving a protocol amendment.  
Sponsor Registered Address:
GlaxoSmithKline Research & Development Limited
980 Great West Road
Brentford
Middlesex, TW8 9GS
UK
In some countries, the clinical trial sponsor may be the local GlaxoSmithKline affiliate 
company (or designee). If applicable, the details of the alternative Sponsor and contact 
person in the territory will be provided to the relevant regulatory authority as part of the 
clinical trial application.
Regulatory Agency Identifying Number(s):  
Compound Number
IND Number
EudraCT Number
GSK3052230
IND#114083
2013-000354-21
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INVESTIGATOR PROTOCOL AGREEMENT PAGE
For protocol number FGF117360:
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


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TABLE OF CONTENTS
PAGE
LIST OF ABBREVIATIONS...........................................................................................11
PROTOCOL SYNOPSIS...............................................................................................14
1.
INTRODUCTION....................................................................................................17
1.1.
The FGF Pathway in Cancer.......................................................................17
1.2.
Lung Cancer...............................................................................................17
1.3.
Mesothelioma .............................................................................................18
1.4.
GSK3052230..............................................................................................18
1.4.1.
Background .................................................................................18
1.4.1.1.
Preclinical data on GSK3052230................................18
1.4.2.
First-time-in-human study FP1039-001........................................19
1.4.2.1.
Clinical Pharmacokinetics of GSK3052230.................20
1.4.2.2.
Clinical Safety of GSK3052230 ..................................20
1.4.2.3.
Anti-tumor Activity with GSK3052230 .........................21
1.5.
Chemotherapy (Paclitaxel, Carboplatin, Docetaxel, Pemetrexed, 
Cisplatin).....................................................................................................21
1.5.1.
Paclitaxel/Carboplatin ..................................................................21
1.5.2.
Docetaxel.....................................................................................22
1.5.3.
Pemetrexed/Cisplatin...................................................................22
1.6.
Summary of Risk Management...................................................................23
2.
OBJECTIVES AND ENDPOINTS...........................................................................26
2.1.
Primary.......................................................................................................26
2.2.
Secondary ..................................................................................................26
2.3.
Exploratory .................................................................................................27
3.
STUDY POPULATION...........................................................................................28
3.1.
Number of Subjects ....................................................................................28
3.2.
Subject Selection Criteria............................................................................28
3.2.1.
Inclusion Criteria..........................................................................28
3.2.2.
Exclusion Criteria.........................................................................30
4.
INVESTIGATIONAL PLAN.....................................................................................32
4.1.
Discussion of Study Design ........................................................................32
4.2.
GSK3052230 plus Chemotherapy ..............................................................33
4.2.1.
Arm A ..........................................................................................34
4.2.2.
Arm B ..........................................................................................35
4.2.3.
Arm C ..........................................................................................35
4.2.4.
Dose-Limiting Toxicity..................................................................36
4.2.5.
Maximum Tolerated Dose............................................................36
4.2.6.
Intra-Subject Dose Escalation or Dose De-escalation..................37
4.2.6.1.
Alternative Dosing and Schedule Cohorts ..................37
4.3.
Rationale ....................................................................................................37
4.3.1.
Rationale for Evaluation of GSK3052230 in Chemotherapy 
Combinations...............................................................................37
4.3.2.
Rationale for Dose of GSK3052230.............................................37
4.3.3.
Rationale for Endpoints................................................................38
4.4.
Study Treatment Assignment......................................................................38


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4.5.
Dosage and Administration of Study Treatments ........................................38
4.5.1.
GSK3052230...............................................................................38
4.5.1.1.
Study treatments: Alternative Dosing and 
Schedule cohorts........................................................38
4.5.2.
Paclitaxel + Carboplatin ...............................................................39
4.5.3.
Docetaxel.....................................................................................40
4.5.4.
Pemetrexed and Cisplatin............................................................40
4.6.
Safety Management Guidelines..................................................................41
4.6.1.
Liver Chemistry Stopping Criteria ................................................41
4.6.1.1.
Liver Chemistry Follow-up Procedures .......................41
4.6.2.
QTc Stopping Criteria ..................................................................43
4.6.3.
Left Ventricular Ejection Fraction (LVEF) and Valvular 
Toxicity Stopping Criteria.............................................................44
4.6.3.1.
LVEF Stopping Criteria...............................................44
4.6.3.2.
Cardiac Valve Toxicity Stopping Criteria.....................44
4.6.4.
Management of Diarrhea .............................................................45
4.6.5.
Management of Fluid Retention...................................................45
4.7.
Dose Modifications .....................................................................................46
4.7.1.
Dose Delays ................................................................................46
4.7.2.
Hematologic Toxicity Related to Chemotherapy...........................46
4.7.3.
Non-hematologic Toxicity Related to Chemotherapy ...................47
4.7.4.
GSK3052230 Dose Modifications ................................................49
4.7.4.1.
GSK3052230 Dose Modifications regarding 
infusion related reactions............................................49
5.
INVESTIGATIONAL PRODUCT.............................................................................50
5.1.
Description of Investigational Products .......................................................50
5.1.1.
GSK3052230...............................................................................50
5.1.2.
Chemotherapeutic Agents ...........................................................50
5.2.
Preparation/Handling/Storage of GSK3052230...........................................51
5.3.
Product Accountability ................................................................................51
5.4.
Treatment Compliance................................................................................51
5.5.
Treatment of Study Treatment Overdose....................................................52
6.
COMPLETION OR WITHDRAWAL OF SUBJECTS...............................................52
6.1.
Screen Failures...........................................................................................52
6.2.
Subject Completion Criteria ........................................................................52
6.3.
Permanent Discontinuation from Study Treatment......................................52
6.4.
Study Completion .......................................................................................53
6.5.
Treatment after the End of the Study ..........................................................53
7.
STUDY ASSESSMENTS AND PROCEDURES .....................................................53
7.1.
Time and Events Table...............................................................................54
7.2.
Demographic/Medical History and Baseline Assessments..........................60
7.2.1.
Critical Baseline Assessments.....................................................60
7.3.
Safety Evaluations......................................................................................60
7.3.1.
Physical Examinations.................................................................61
7.3.2.
ECOG Performance Status..........................................................61
7.3.3.
Vital Signs....................................................................................61
7.3.4.
Forced Vital Capacity...................................................................61
7.3.5.
Electrocardiogram........................................................................61
7.3.6.
Echocardiogram...........................................................................61


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7.3.7.
Ophthalmologic Examinations......................................................62
7.3.8.
Laboratory Assessments .............................................................62
7.3.9.
Pregnancy Testing and Reporting................................................63
7.4.
Evaluation of Anti-Cancer Activity ...............................................................64
7.4.1.
Evaluation of Response in Arm A and Arm B (RECIST 
1.1) ..............................................................................................66
7.4.1.1.
Evaluation of target lesions.........................................66
7.4.1.2.
Evaluation of non-target lesions..................................67
7.4.1.3.
New lesions................................................................67
7.4.1.4.
Evaluation of overall response....................................67
7.4.1.5.
Evaluation of best overall response............................68
7.4.2.
Evaluation of Response in Arm C: Mesothelioma ........................69
7.4.2.1.
Mesothelioma Tumor Imaging ....................................69
7.4.2.2.
Prior Scan collection...................................................70
7.4.3.
Patient Reported Outcomes.........................................................70
7.5.
Pharmacokinetics .......................................................................................71
7.5.1.
Blood Sample Collection for Pharmacokinetics............................71
7.5.2.
Pharmacokinetic Sample Analysis ...............................................71
7.6.
Immunogenicity...........................................................................................71
7.7.
Translational Research...............................................................................72
7.7.1.
Central Confirmation of FGF Signalling Pathway Status 
and Translational Research .........................................................72
7.7.2.
Peripheral Blood ..........................................................................72
7.7.2.1.
Plasma for Soluble Markers........................................72
7.7.2.2.
Circulating cell free DNA (cfDNA) Analysis.................73
7.8.
Pharmacogenetics......................................................................................73
8.
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS.....................................74
8.1.
Definition of an AE......................................................................................74
8.2.
Definition of a SAE......................................................................................75
8.3.
Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as SAEs.....................................................................................76
8.4.
Laboratory and Other Safety Assessment Abnormalities Reported 
as AEs and SAEs .......................................................................................76
8.5.
Time Period and Frequency of Detecting AEs and SAEs............................76
8.5.1.
Method of Detecting AEs and SAEs.............................................77
8.5.2.
Prompt Reporting of SAEs and Other Events to GSK ..................77
8.5.3.
Regulatory reporting requirements for SAEs................................78
9.
CONCOMITANT MEDICATIONS AND NON-DRUG THERAPIES .........................79
9.1.
Permitted Medication(s)..............................................................................79
9.2.
Prohibited Medications................................................................................79
9.3.
Permitted Non-Drug Therapies ...................................................................80
10. LIFESTYLE AND/OR DIETARY RESTRICTIONS..................................................80
10.1.
Contraception .............................................................................................80
10.1.1.
Female Subjects..........................................................................80
10.1.2.
Male Subjects..............................................................................81
11. DATA MANAGEMENT ...........................................................................................82
12. DATA ANALYSIS AND STATISTICAL CONSIDERATIONS...................................82


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12.1.
Considerations of statistical design.............................................................82
12.2.
Hypotheses.................................................................................................82
12.3.
Sample Size Determination ........................................................................83
12.3.1.
Arm A: GSK3052230 + Paclitaxel + Carboplatin ..........................83
12.3.2.
Arm B: GSK3052230 + Docetaxel................................................83
12.3.3.
Arm C: GSK3052230 + Pemetrexed + Cisplatin...........................84
12.4.
Sample Size Sensitivity...............................................................................84
12.4.1.
Sample Size Re-estimation..........................................................84
12.5.
Data Analysis Considerations .....................................................................84
12.5.1.
Analysis Populations....................................................................84
12.6.
Treatment Comparisons .............................................................................85
12.7.
Interim Analysis ..........................................................................................85
12.8.
Key Elements of Analysis Plan ...................................................................88
12.8.1.
Anti-Cancer Activity Analyses ......................................................89
12.8.2.
Safety Analyses...........................................................................89
12.8.2.1.
Extent of Exposure .....................................................89
12.8.2.2.
Adverse Events ..........................................................89
12.8.2.3.
Clinical Laboratory Evaluations ..................................89
12.8.2.4.
Other Safety Measures...............................................90
12.8.3.
Patient Reported Outcomes.........................................................90
12.8.4.
Pharmacokinetic Analyses...........................................................90
12.8.5.
Pharmacokinetic/Pharmacodynamic Analyses.............................90
12.8.6.
Tumor Kinetics Analysis...............................................................91
12.8.7.
Translational Research Analyses.................................................91
12.8.8.
Pharmacogenetic Analyses .........................................................92
13. STUDY CONDUCT CONSIDERATIONS ...............................................................92
13.1.
Posting of Information on Clinicaltrials.gov..................................................92
13.2.
Regulatory and Ethical Considerations, Including the Informed 
Consent Process ........................................................................................92
13.3.
Urgent Safety Measures .............................................................................92
13.4.
Quality Control (Study Monitoring) ..............................................................93
13.5.
Quality Assurance.......................................................................................93
13.6.
Study and Site Closure ...............................................................................93
13.7.
Records Retention......................................................................................94
13.8.
Provision of Study Results to Investigators, Posting of Information 
on Publicly Available Clinical Trials Registers and Publication....................94
14. REFERENCES.......................................................................................................96
15. APPENDICES......................................................................................................102
15.1.
Appendix 1: Pharmacogenetics (PGx) ......................................................102
15.2.
Appendix 2: NYHA Functional Classification System ................................107
15.3.
Appendix 3: COCKCROFT-GAULT FORMULA ........................................108
15.4.
Appendix 4: ECOG Performance Status1..................................................109
15.5.
Appendix 5: Liver Chemistry Monitoring, Interruption Stopping and 
Follow-up Criteria......................................................................................110
15.6.
Appendix 6: Urine Protein Creatinine (UPC) Ratio....................................111
15.7.
Appendix 7: Country Specific Requirements.............................................112
15.8.
Appendix 8: Protocol Amendment Changes..............................................113


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LIST OF ABBREVIATIONS
AE(s)
Adverse Event(s)
ADA
Anti-drug antibody
AIDS
Acquired immunodeficiency syndrome
ALP
Alkaline phosphatase
ALT
Alanine aminotransferase
AML
Acute myeloid leukemia
ANC
Absolute neutrophil count
AST
Aspartate aminotransferase
AUC(0-)
Area under the concentration-time curve over the dosing interval
-HCG
Beta-Human Chorionic Gonadotropin
BSA
Body surface area
BUN
Blood urea nitrogen
CAF
Cytokines and Angiogenic Factors
Cav
Average concentration
CBC
Complete blood count
CfDNA
Circulating cell free DNA
CL
Systemic clearance of parent drug
CLCR
Creatinine clearance
Cmax
Maximum observed concentration 
CT
Computed tomography
Cτ
Pre-dose (trough) concentration at the end of the dosing interval
CO2
Carbon dioxide
CPMS
Clinical Pharmacokinetic Modeling and Simulation
CNS
Central nervous system
CR
Complete response
Ct
Last observed quantifiable concentration
DLT
Dose-limiting toxicity
DNA
Deoxyribonucleic acid
EC
Ethics committee
ECG(s)
Electrocardiogram(s)
ECHO
Echocardiogram
ECL
Electrochemiluminescent
ECOG
Eastern Cooperative Oncology Group
eCRF
Electronic case report form
EGF
Endothelial growth factor
FDA
Food and Drug Administration
FGF
Fibroblast growth factor
FGFR1
Fibroblast growth factor receptor 1
FISH
Fluorescence in situ hybridization
FSH
Follicle Stimulating Hormone
FTIM
First time in man
GCP
Good Clinical Practice
GFR
Glomerular filtration rate 
GGT
Gamma glutamyltransferase


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GSK
GlaxoSmithKline
HIV
Human Immunodeficiency Virus
h/hr
Hour(s)
IB
Investigator’s Brochure
ICH
International Conference on Harmonization
IEC
Independent Ethics Committee
IgG1
Immunoglobulin G1
IHC
Immunohistochemistry
IND
Investigational New Drug
INR
International normalization ratio
IP
Investigational Product
IRB
Institutional Review Board
IU
International Unit
IV
Intravenous
kg
Kilogram
L
Liter
LDT/IUO
Laboratory developed test for investigational use only
LLN
Lower limit of normal
LVEF 
Left Ventricular Ejection Fraction
MedDRA
Medical Dictionary for Regulatory Activities
mg
Milligrams
mL
Milliliter
msec
Milliseconds
MFD
Maximum Feasible Dose
MPM
Malignant pleural mesothelioma
MRI
Magnetic resonance imaging
MTD
Maximum tolerated dose
NSCLC
Non-small cell lung cancer
NCI-CTCAE
National Cancer Institute - Common Terminology Criteria for Adverse 
Events
NYHA
New York Heart Association
ORR
Overall response rate
PD
Progressive disease or pharmacodynamics
PET
Probability of early termination
PFS
Progression-free survival
PGx
Pharmacogenetics
PK
Pharmacokinetic
PO
Per os, by mouth
PR
Partial response
PTT
Partial thromboplastin time
QTc
Corrected QT interval duration
QTcB
QT interval corrected for heart rate by Bazett’s formula
QTcF
QT interval corrected for heart rate by Fridericia’s formula
RAMOS
Registration and Medication Ordering System
RAP
Reporting and Analysis Plan
RBC
Red blood cells


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RECIST
Response Evaluation Criteria in Solid Tumors
RNA
Ribonucleic acid
SAE
Serious adverse event(s)
SCCHN
Squamous cell carcinoma of the head and neck
SD
Standard deviation or stable disease
SMRP
Soluble mesotheline-related peptides
SPM
Study Procedures Manual
t
Time of last observed quantifiable concentration
t1/2
Terminal phase half-life
τ
Dosing interval
TGI
tumor growth inhibition 
TSH
Thyroid stimulating hormone
TTG
Time to tumor growth
ULN
Upper limit of normal
UK
United Kingdom
UPC
Urine protein creatinine
US/USA
United States/United States of America
Vd
Apparent volume of distribution after IV administration
WBC
White blood cells
Trademark Information
Trademarks of the GlaxoSmithKline 
group of companies
Trademarks not owned by the 
GlaxoSmithKline group of companies
NONE
Alimta
Paraplatin
Platinol
Taxol
Taxotere


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PROTOCOL SYNOPSIS
Title: Multi-arm, Non-randomized, Open-Label Phase IB Study to Evaluate 
GSK3052230 in Combination with Paclitaxel and Carboplatin, or Docetaxel or as Single 
Agent in Subjects with Solid Malignancies and Deregulated FGF Pathway Signaling
Protocol Number: FGF117360
Clinical Phase: IB
Compound: GSK3052230
Study Rationale: FGF receptor 1 (FGFR1) amplification has been identified in 
approximately 20% of squamous non-small cell lung cancer (NSCLC) with suggested 
tumor dependence on fibroblast growth factor (FGF) pathway signaling in this subset. 
FGFR1 amplification has been associated with significantly shorter disease free and 
overall survival in NSCLC [Kim, 2013]. GSK3052230 inhibits the FGF pathway through 
binding and sequestering of FGF ligands and has demonstrated tumor growth inhibition 
in several tumor xenograft models [Harding, 2013]. Carboplatin and paclitaxel can be 
used in first line therapy of metastatic NSCLC and docetaxel is a standard second line 
agent. Additive antitumor effect was demonstrated in tumor xenograft models treated 
with the combination of GSK3052230 and chemotherapy including paclitaxel and 
carboplatin as well as docetaxel. Based on the clinical and preclinical data, the 
combination of GSK3052230 in combination with chemotherapy will be investigated in 
patients with metastatic squamous NSCLC in Arms A and B.
FGF ligand-dependent signaling plays an important role in cancer development and 
tumor maintenance. GSK3052230 has been shown to inhibit tumor growth in non-
amplified FGFR1 tumor xenograft models where FGF2 mRNA was overexpressed 
[Harding, 2013]. Malignant pleural mesothelioma (MPM) is a tumor type where FGF2 
ligand overexpression has been observed in a high percentage of primary specimens and 
where GSK3052230 preclinical efficacy has been observed in xenograft models. 
Pemetrexed and cisplatin are standard agents used in first line therapy of MPM. In Arm 
C, the combination of GSK3052230 and pemetrexed + cisplatin will be investigated in 
patients with MPM who are not surgically resectable or have relapsed after surgery or 
localized treatment.
Study Design: This will be a multi-arm, multicenter, non-randomized, parallel-group, 
uncontrolled, open-label Phase IB study designed to evaluate the safety, tolerability and 
preliminary activity of GSK3052230 in combination with paclitaxel + carboplatin in 
previously untreated metastatic squamous NSCLC (Arm A), in combination with 
docetaxel in metastatic squamous NSCLC that has progressed after at least 1 line of 
chemotherapy (Arm B), or in combination with pemetrexed + cisplatin in MPM 
previously untreated with chemotherapy or investigational agents (Arm C). 
Objectives and Endpoints:
The primary objectives and endpoints are noted below. The full objectives and endpoints 
(primary, secondary andexploratory) are located in the main protocol in Section 2.


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Primary Objectives:

To characterize the safety and tolerability of GSK3052230 in combination with 
chemotherapy regimens.

To determine the regimen of GSK3052230 in combination with chemotherapy for 
evaluation in future studies based on the maximum tolerated dose (or maximum
feasible dose).

To assess the overall response rate (ORR) in each treatment arm.
Primary Endpoints:

Measurements used to evaluate safety and tolerability will include rate and severity 
of adverse events (AEs), withdrawals due to AEs, dose interruptions and reductions, 
treatment duration, and dose-limiting toxicities (DLTs) as well as change from 
baseline for the following: physical examinations, vital signs,12-lead 
electrocardiograms (ECGs), echocardiograms (ECHO), clinical laboratory tests.

Maximum tolerated dose (MTD) or maximum feasible dose (MFD).

Best response defined as complete or partial response, stable disease or progressive 
disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. 
ORR defined as the proportion of subjects with investigator-assessed confirmed 
complete response or partial response per RECIST 1.1.
Hypotheses:
Arm A: H0: p≤25% versus HA:p≥45%
Arm B: H0: p≤10% versus HA:p≥25%
Arm C: H0:p≤40% versus HA: p≥60%
Number of Subjects: Approximately 70 subjects (minimum of 38 and up to 120, 
alternative dosing cohorts could potentially add another 6 to ~40 subjects).
Inclusion Criteria: A high level summary of the inclusion and exclusion criteria are 
denoted below. The full details of inclusion and exclusion criteria are located in the main 
protocol Section 3.2.
1.
Histologically or cytologically confirmed diagnosis:
Arms A and B: Stage IIIB or IV or recurrent metastatic squamous NSCLC (TNM 
Staging for NSCLC, 7th Edition) with FGFR1 gene amplification by central 
laboratory testing.
Arm C: recurrent after local treatment or unresectable MPM with measurable 
lesions.

For specific arms the following requirements:
Arm A: Subjects who have received no prior therapy for Stage IV or recurrent 
metastatic disease. Note, to avoid any undue delay of initiating systemic
chemotherapy for these subjects with newly diagnosed metastatic disease, it is 
allowed to initiate the first cycle of chemotherapy while eligibility for the study is 


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still being determined, as long as the first dose of GSK3052230 is given no later than 
Cycle 2 Day 1 of chemotherapy.
Arm B: Subjects who have documented tumor progression (based on radiological 
imaging), or intolerability, after receiving only at least prior line of platinum 
containing combination chemotherapy for metastatic disease. 
Arm C: Subjects who have received no prior systemic therapy for MPM.
2.
Availability of archival tumor tissue required. If archival tissue is not available, a 
fresh biopsy is required.
3.
Measurable disease per RECIST version 1.1 for Arms A & B and by modified 
RECIST for Arm C.
4.
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 for Arm A
and C and 0-2 for Arm B. 
Exclusion Criteria:
1. For Arms A,  C: Treatment with any FGFR inhibitor.
For Arm B: Treatment with any anti-cancer therapy (for biological anti-cancer 
therapies see criteria 2.) during the preceding 4 weeks or within 4 half-lives of the 
therapy, whichever is longer.
2. Receipt of any biological therapy within 6 weeks of the first dose of GSK3052230.
3. Conditions likely to increase the potential for abdominal perforation or fistula 
formation.
4. Symptomatic leptomeningeal or brain metastases or spinal cord compression.
Study Treatment Dose/Route/Regimen: GSK3052230 will be administered via 
intravenous infusion (i.v.) once weekly in each 21-day cycle. GSK3052230 will be 
diluted in a 250 mL (nominal volume) i.v. bag containing either 5% dextrose solution or 
normal saline and administered over 30 minutes. Paclitaxel and carboplatin (Arm A), 
docetaxel (Arm B), and pemetrexed and cisplatin (Arm C) will be administered per 
product label on Day 1 of each cycle.
Study Assessments: Prior to starting the study informed consent will be obtained from 
all subjects. Safety assessments and study procedures include: medical history, review 
inclusion/exclusion criteria, physical exam, vital signs, weight, height, ophthalmologic 
exam, ECHO, Eastern Cooperative Oncology Group Performance Status (ECOG PS), 
laboratory assessments (hematology, coagulation, pancreatic markers, chemistry, thyroid, 
pregnancy, urinalysis), ECG, and immunogenicity sampling. Radiologic and disease 
assessments include brain scan and bone scan. Patient reported outcomes will be assessed 
using the Lung Cancer Symptom Scale or Lung Cancer Symptom Scale Mesothelioma 
[LCSS(-meso)]. Additional samples (blood, plasma or tissue) will be obtained for 
pharmacokinetic, pharmacodynamic, or translational research.  An optional 
pharmacogenetic blood sample may be obtained if subject consents.


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1.
INTRODUCTION
1.1.
The FGF Pathway in Cancer
Preclinically, the fibroblast growth factor (FGF) pathway plays many roles in the 
development of cancer, including regulation of cell growth and differentiation, regulation 
of angiogenesis and participation in tumor-stroma interactions. FGFs can stimulate the 
proliferation of tumor cells and tumor cell lines. Blockade of FGF signaling can prevent 
tumor cell growth [Lamont, 2011].
There are 22 known human FGFs (for a review on FGFs and their role in cancer see 
[Beenken, 2009]. The expression of the FGFs is restricted to specific tissues, cell types, 
and/or developmental stages with the exception of FGF-1 and FGF-2, both of which are 
expressed in essentially all adult tissues.  FGF signaling is mediated by a family of trans-
membrane receptor tyrosine kinases encoded by four distinct genes producing FGF 
receptor subtypes termed FGFR1-4.  Many FGFs bind with high affinity to multiple FGF 
receptors, and as such, each FGF receptor has a characteristic binding profile.  The FGF 
proteins trigger their 4 cognate receptor tyrosine kinases (FGFRs) to generate a range of 
cellular proliferation, survival, and differentiation responses [Itoh, 2007].
FGFR1 is the best characterized of the 4 FGFRs. FGFR1 acts through multiple 
mechanisms in the promotion of tumor cell growth and survival. FGFR1 signaling 
increases the mitotic rate of tumor cells, promotes tumor angiogenesis, and helps 
maintain the tumorigenicity of tumor stem cells. Many tumor cell lines are responsive to 
and dependent on FGFR1 signaling for growth in vitro, and tumor cell lines become 
resistant to cytotoxic agents when stimulated with FGF2 [Song, 2000]. 
FGF ligand-dependent signaling occurs through autocrine production of FGFs directly 
from cancer cells or through paracrine production of FGFs from the local stroma [Turner, 
2010]. FGF2-FGFR1 autocrine feedback loops have been characterized in several tumor 
types and may have a role in drug resistance upon exposure to chemotherapy or targeted 
agents such as gefitinib [Sharpe, 2011; Marek, 2009]. Overexpression of FGFs is readily 
detectable by immunohistochemical approaches, as several studies have shown high 
levels of FGF2 protein in MPM tumor specimens [Kumar-Singh, 1999; Davidson, 2004; 
Li, 2011]. Further, overexpression or high systemic levels of FGF ligands correlate with 
tumorigenesis and poor patient outcome. These discoveries support the notion that 
specific treatments targeting FGF pathway alterations may provide benefit in this 
population.
1.2.
Lung Cancer
Various in vitro studies utilizing non-small cell lung cancer (NSCLC) cell lines reveal 
that specific FGFs (FGF2 and FGF9) as well as FGFR1 and FGFR2 are frequently co-
expressed [Berger, 1999; Chandler, 1999; Fischer, 2008; Kono, 2009].  In addition, 
frequent expression of FGF2, FGFR1 and FGFR2 mRNA and protein in primary NSCLC 
specimens have been demonstrated [Kono, 2009]. Further it has been shown that FGFR1
gene amplification is associated with sensitivity to FGFR1 inhibition in non-small cell 
lung cancer (NSCLC) cell lines [Dutt, 2011]. 


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Increased expression of FGFRs, FGFR1 gene amplification, or production of FGFs 
correlates with poor prognosis in a variety of tumor types including NSCLC [Nguyen, 
1994; Kim, 2013]. A focal amplification of the FGFR1 gene has been detected in 
approximately 20% of subjects with squamous NSCLC [Weiss, 2010], a histological 
subtype of NSCLC which previously had very limited evidence of molecular alterations 
amenable to targeted drug therapy. 
1.3.
Mesothelioma
Malignant mesothelioma remains a deadly disease with few effective therapies. Although 
the incidence of mesothelioma is leveling off in the United States, the incidence in 
Western Europe, China, Russia, and India continues to rise [Ettinger, 2012]. The median 
overall survival ranges from 9-17 months regardless of disease stage [Tsao, 2009]. The 
standard of care for the front-line treatment of mesothelioma remains cisplatin and 
pemetrexed with the combination regimen having a 41% response rate, a median time to 
progression of 5.7 months, a median overall survival of 12.1 months, and significant 
improvements in quality of life [Vogelzang, 2003; Gralla, 2003]. There remains no 
widely approved regimen for recurrent mesothelioma although pemetrexed (if not used in 
the front-line), vinorelbine, and gemcitabine are agents that have been used with limited 
success [Jassem, 2008; Stebbing, 2009; Manegold, 2005]. A recently completed Phase III 
study of vorinostat versus placebo in 660 patients with recurrent mesothelioma reported a 
median progression-free survival (PFS) of 6.3 versus 6.1 weeks and median overall 
survival (OS) of 31 versus 27 weeks in vorinostat vs. placebo respectively, which 
represents the largest Phase III study completed to date in recurrent mesothelioma 
[Krug, 2011]. These poor PFS and OS data underscore the need for more effective 
therapies in recurrent mesothelioma.
1.4.
GSK3052230
1.4.1.
Background
GSK3052230 was originally developed as FP1039 and was also briefly known as 
HGS1036. All three names refer to the same molecular entity and differ only in the 
extinction coefficient used to calculate the concentration of drug. Please refer to the 
Investigators Brochure (IB) for additional details [GlaxoSmithKline Document Number
2013N160379_00].
GSK3052230 is a soluble fusion protein consisting of the extracellular domains of human 
fibroblast growth factor receptor 1 (FGFR1) isoform α-IIIc linked to the modified hinge 
and native Fc regions of human immunoglobulin G1 (IgG1).  GSK3052230 acts as a 
fusion protein “trap” that sequesters FGFs that may be involved in the growth of tumor 
cells or the associated vasculature mediated by FGFRs. In this manner, GSK3052230 
may have anti-tumor activity either by inhibiting tumor cell proliferation and/or by 
inhibition of tumor associated angiogenesis. 
1.4.1.1.
Preclinical data on GSK3052230
Seventy-eight tumor-derived xenograft models were treated with GSK3052230 (FP1039) 
as a single agent.  Twenty-eight models were found to show significant tumor growth 


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inhibition (TGI), including models of NSCLC, small cell lung cancer, mesothelioma, 
squamous cell carcinoma of the head and neck (SCCHN), endometrial, colon and breast 
cancer [Harding, 2010; Harding, 2013].  In lung cancer xenografts, GSK3052230-teated 
tumors harboring FGFR1 gene amplification displayed an average of 56% TGI compared 
to 22% TGI in non-amplified FGFR1 xenografts (p=0.03)[Harding, 2013]. FGF2 mRNA 
levels displayed the highest ratio (247.7-fold) of median gene expression between 
GSK3052230 responder and nonresponder xenograft models and was the only marker 
that correlated with response in the subset of non-amplified FGFR1 lung cancer 
xenografts where significant tumor growth inhibition was observed [Harding, 2013]. 
To further extend this observation, GSK3052230 was tested in models of mesothelioma, 
a tumor type shown to express high levels of FGF2 mRNA in cell lines and in primary 
tumor specimens [DeYoung, 2014]. GSK3052230 inhibited MAPK signaling as 
evidenced by decreased phospho-ERK levels in both NCI-H226 and MSTO-211H cells. 
When both cell lines were grown as tumor xenografts in mice, GSK3052230 inhibited 
tumor growth in a dose-dependent manner (NCI-H226: 16 – 78% TGI; MSTO-211H: 20 
– 50% TGI). Because FGFs also play a key role in angiogenesis, the effects of 
GSK3052230 on tumor vessel formation in NCI-H226 xenografts were explored 
[DeYoung, 2014]. Dose-dependent and statistically-significant reductions in tumor vessel 
density were observed in GSK3052230-treated tumors compared to vehicle-treated 
tumors using MECA-32 endothelial cell IHC staining. Therefore, FGFR1 amplification 
or FGF2 overexpression served as predictive markers of response to GSK3052230.
An additional thirty tumor xenograft models were treated with GSK3052230 in 
combination with other anti-cancer agents including chemotherapy and targeted agents. 
In general, the combination of GSK3052230 and a second agent was more effective than 
either GSK3052230 or the other agent when administered alone. In A549 lung 
xenografts, GSK3052230 treatment (15 mg/kg) alone resulted in 42% tumor inhibition 
(not significant). Carboplatin (25 mg/kg) plus paclitaxel (30 mg/kg) alone resulted in 
73% tumor inhibition (p < 0.001), and carboplatin plus paclitaxel and GSK3052230 
resulted in 86% tumor inhibition (p < 0.001) compared to vehicle treated animals. In two 
prophylactic models (A549 and NCI-H1703) the combination of GSK3052230 and 
docetaxel showed tumor growth inhibition of 58% (p < 0.01) and 97% (p < 0.001) 
compared to 46% and 26% with GSK3052230 alone (both not significant).  In these three 
models, the addition of GSK3052230 did not confer additional toxicity compared to 
chemotherapy alone [GlaxoSmithKline Document Number 2013N160379_00].
1.4.2.
First-time-in-human study FP1039-001
GSK3052230 has been studied in a Phase 1, open-label, dose-escalation study (Protocol 
FP1039-001, please refer to Investigator Brochure, GlaxoSmithKline Document Number 
2013N160379_00).  No maximum tolerated dose (MTD) was identified in this study 
exploring a dose range from 0.6 to 20 mg/kg/week of GSK3052230.  The 20 mg/kg once 
weekly dosing schedule was determined to be safe and was declared the ‘maximum 
feasible dose’ (MFD) taking into account the high absolute dose of drug as well as 
achievement of the desired target concentration based on preclinical studies.


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1.4.2.1.
Clinical Pharmacokinetics of GSK3052230
In study FP1039-001, the GSK3052230 PK profiles were assessed following the 1st and 
4th doses and were found to be typical of a large protein, with an initial distribution phase 
and a terminal elimination phase.  The profile in humans is similar to that observed in 
rats, dogs, and chimpanzees.  After the 1st dose, the mean terminal phase half-life (t1/2) 
ranged from 63 to 92 h, while after the 4th dose t1/2 ranged from 87 to 125 h. Systemic 
clearance (CL) ranged from 0.0648 to 0.101 L/h across the dose range and appears to be
independent of dose.  The maximum plasma GSK3052230 concentration (Cmax) and 
area under the plasma GSK3052230 concentration-time curve during a dosing interval 
(AUC(0-)) increased proportionally to dose.  Some accumulation was observed after 4 
weekly doses; Cmax after the 4th infusion was 11% to 42% higher than Cmax after the 
1st dose, and AUC(0-) was 30% to 61% higher after the 4th dose compared to the 1st 
dose.  The pharmacokinetic analysis supports a weekly IV dosing schedule of between 10 
and 20 mg/kg, when used as monotherapy, achieving the desired target concentration 
throughout the dosing interval.
1.4.2.2.
Clinical Safety of GSK3052230
GSK3052230 has been investigated as monotherapy in a first-time-in-man (FTIM) study 
(FP1039-001) including a total of 39 subjects with different tumor types. It should be 
noted that the study population was heavily pretreated with a median of 4 prior anticancer 
therapies (range 0-11). GSK3052230 IV once every week was considered tolerable over 
the dose range studied (0.6-20 mg/kg/week).  Mean duration of exposure was 54 days 
(13-203 days). One subject required a dose reduction (Grade 3 neutropenia event 
described below) and a total of 6 subjects experienced dose interruptions at any timepoint 
during the study. 
A total of 4 dose-limiting toxicities (DLTs) were reported over the course of the study 
and occurred at doses of 1.0 mg/kg (urticaria), 1.3 mg/kg (intestinal perforation and 
neutropenia each counted as an event), and 20 mg/kg (muscular weakness). After seeing 
2 DLTs at 1.3 mg/kg/week, 2 dose levels below 1.3 mg/kg were explored in 6 subjects 
each. Both these dose levels were considered tolerable.  Since the DLT of intestinal 
perforation was confounded by several known risk factors and of questionable relation to 
GSK3052230 (see below) and the DLT of neutropenia was a brief Grade 3 event, further 
exploration of this dose-level for a total of 6 subjects was carried out. Since there were no 
further DLTs at this dose level, dose escalation continued.  No clear evidence of dose-
related toxicity limiting the dose escalation was found, hence a MTD was not identified, 
rather, a ‘maximum feasible dose’ of 20 mg/kg was determined. 
The most common toxicities were diarrhea (44%), fatigue (44%) and nausea (26%), with 
no clear dose-related increases in frequency of any adverse events (AEs) except low 
grade nausea/vomiting seen at the highest dose-level.
The more commonly reported Grade 3 (severe) AEs involved metabolism and nutrition 
disorders as reflected in abnormal clinical chemistry values, reported for 7 subjects 
(17.9%) and consisted of hyperglycemia, hypokalemia, and hypophosphatemia (each 
reported by 2 subjects [5.1%]).  Of note, hyperphosphatemia that has been previously 
reported with agents targeting the FGF pathway was not identified in the study.  Other 


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Grade 3 AEs reported by more than 1 subject were abdominal pain and dyspnea (each 
reported by 2 subjects [5.1%]).  A total of 2 subjects had Grade 4 and/or fatal AEs (1 
subject with Grade 4 pulmonary embolism and 1 subject with Grade 4 leukopenia, Grade 
4 neutropenia, and Grade 5 respiratory failure).
A total of 12 serious adverse events (SAEs) were reported in 11 subjects during the 
course of this study.  Two SAEs, intestinal perforation and worsening bilateral leg 
weakness/peripheral neuropathy, were considered at least possibly related to 
GSK3052230.  Intestinal perforation occurred in a subject with malignant liposarcoma of 
the retroperitoneum treated with several resections and abdominal radiotherapy, who died 
of intestinal perforation 17 days after last dose of GSK3052230.  The tumor mass 
involved the bowel at study entry; this was also a DLT event.  The second subject 
developed exacerbation of pre-existing bilateral leg weakness and died of acute 
respiratory failure secondary to pneumonia 43 days after last dose of GSK3052230.  The 
subject had colon cancer with metastatic spread to the lungs, and had pre-existing 
peripheral neuropathy since 2005.  After 3 weeks on study the neuropathy worsened and 
GSK3052230 was discontinued.  MRI of brain and spinal cord was normal and the 
subject was transferred to a rehabilitation facility where he died 19 days later.
A total of five deaths were reported in the study.  Please refer to the Investigator 
Brochure, GlaxoSmithKline Document Number 2013N160379_00, for further details.
1.4.2.3.
Anti-tumor Activity with GSK3052230
No activity in terms of objective tumor responses were seen in the FTIM study which 
was carried out in a population unselected for deregulation of FGF signaling pathway. 
For subjects with evaluable disease, the best overall tumor response (Response 
Evaluation Criteria in Solid Tumors [RECIST] 1.0) was stable disease (SD) for 15/36 
subjects (41.7%) and progressive disease (PD) for 17/36 subjects (47.2%). One subject 
with hormone resistant prostate cancer rapidly progressing on prior docetaxel, 
experienced a 20% reduction in tumor diameter and stable disease of 7 months duration.
1.5.
Chemotherapy (Paclitaxel, Carboplatin, Docetaxel, 
Pemetrexed, Cisplatin)
1.5.1.
Paclitaxel/Carboplatin
Paclitaxel, a mitotic inhibitor originally extracted from the pacific yew (Taxus 
brevifolia), has been shown to be active as a single agent and/or in combination with 
other chemotherapeutic drugs in subjects with ovarian cancer, breast cancer, NSCLC, and 
Kaposi’s sarcoma.  Paclitaxel causes side effects that are generally predictable and 
manageable. Neutropenia, the most frequent side effect, is generally of short duration.  
Peripheral neuropathy, myalgia, and arthralgia are usually noted with the administration 
of higher doses of paclitaxel (≥ 175 mg/m2) for several cycles. Paclitaxel causes rapid 
and usually complete alopecia.  Other toxicities include: mild to moderate nausea, 
vomiting, diarrhea, and mucositis [Taxol USPI, 2011].
Carboplatin is an analog of cisplatin with an improved toxicity profile. Bone marrow 
suppression is the major dose-limiting toxicity of carboplatin. Carboplatin has been 


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shown to be active as a single agent and/or in combination with other chemotherapeutic 
drugs in subjects with ovarian cancer, NSCLC, bladder cancer, esophageal and other 
upper gastrointestinal cancer [Paraplatin USPI, 2010]. Nausea, vomiting, and loss of 
appetite are usually mild to moderate.  The pharmacokinetics (area under the time 
concentration curve [AUC] and the pharmacodynamic effects (hematologic toxicity) of 
carboplatin are much better predicted by glomerular filtration rate (GFR) based dosing as 
compared with the more traditional body surface area (BSA) dosing method [Calvert, 
1994]. 
The combination of paclitaxel and carboplatin has been developed to avoid overlapping 
neurotoxicity of paclitaxel with cisplatin and for its easier administration.  Several Phase 
2 and Phase 3 studies of the combination of paclitaxel and carboplatin have shown that 
the drug combination is active in subjects with NSCLC, ovarian cancer, bladder cancer, 
esophageal cancers, SCCHN cancers and other tumor types [NCCN Guidelines, 2012]. 
1.5.2.
Docetaxel
Docetaxel, a semi-synthetic analog of paclitaxel, acts by disrupting the microtubule 
network leading to apoptosis and cell death.  Docetaxel is used as a single agent in the 
treatment of NSCLC, breast cancer, and in combination with multiple other 
chemotherapies in the treatment of breast cancer, NSCLC, gastric cancer and SCCHN. 
The most common adverse events associated with the administration of docetaxel are 
infections, neutropenia, anemia, febrile neutropenia, hypersensitivity, thrombocytopenia, 
neuropathy, dysgeusia, dyspnea, constipation, anorexia, nail disorders, fluid retention, 
asthenia, pain, nausea, diarrhea, vomiting, mucositis, alopecia, skin reactions and myalgia 
[Taxotere PI, 2010]. 
1.5.3.
Pemetrexed/Cisplatin
Pemetrexed is a folate analog inhibitor that disrupts folate-dependent metabolic processes 
essential for cell replication. In vitro studies have shown that pemetrexed inhibits
thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide 
formyltransferase, which are folate-dependent enzymes involved in de novo biosynthesis 
of thymidine and purine nucleotides. Cisplatin is a heavy-metal complex containing a 
central platinum atom with 2 chloride atoms and 2 ammonia molecules in the cis 
position. Pemtrexed in combination with cisplatin is recommended for the treatment of 
mesothelioma [Alimta PI, 2004].
The most common adverse reactions (incidence ≥20%) with single-agent use of 
pemetrexed are fatigue, nausea, and anorexia. Additional common adverse reactions 
when used in combination with cisplatin include vomiting, neutropenia, leukopenia, 
anemia, stomatitis/pharyngitis, thrombocytopenia, and constipation [Alimta PI, 2004].
Common adverse reactions (incidence ≥20%) associated with cisplatin include 
nephrotoxicity, ototoxicity, myelosuppression, and nausea/vomiting. Other toxicities 
include vascular complications, serum electrolyte imbalance, Hyperuricemia, 
neurotoxicity, ocular toxicity, anaphylactic-type reactions, and hepatotoxicity [Platinol
PI, 2010].


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1.6.
Summary of Risk Management
Further information on these potential risks can be found in the Investigator Brochure 
(IB) for GSK3052230 [GlaxoSmithKline Document Number 2013N160379_00].
Based on preclinical data and experience from the clinical study, as well as the toxicity 
profile of the combination agents, the following are events of interest:
Infusion-related reactions/Edema/Hypersensitivity: 

Generalized edema of unknown cause (not associated with measurable increase in 
histamine or cytokines) was a prominent observation in preclinical toxicology 
studies

Edema and hypersensitivity are potential overlapping toxicities between 
GSK3052230 and taxanes such as paclitaxel and docetaxel.

Subjects will be closely monitored for infusion-related reactions.

Subjects in the combination chemotherapy arms will already be receiving 
premedication with glucocorticoids (for the paclitaxel combination also 
antihistamines and H2 receptor antagonists) as part of the standard of care. 
Epinephrine for subcutaneous injection, diphenhydramine for IV injection, and any 
other medications and resuscitation equipment for the emergency management of 
anaphylactic reactions must be available in the room where the infusions are being 
performed.

If infusion reactions are noted in subjects not already premedicated with 
glucocorticoids, antihistamines and H2 receptor antagonists, appropriate 
premedication against hypersensitivity reactions may be initiated prior to the next 
infusions at the discretion of the investigator according to the institution’s standard 
practice.  All subjects who have experienced an infusion reaction should have 
GSK3052230 infused over 60 minutes instead of 30 minutes and pre-treated with 
appropriate local pretreatment guidelines. If the subject continues to have a reaction 
on re-challenge, the infusion of GSK3052230 may be prolonged for 90 minutes.
Anti-drug antibodies:

The antidrug antibody response in study FP1039-001 was generally weak with no 
apparent associated changes in drug exposure or clinical sequelae. Anti-drug 
antibodies will be monitored throughout the study.
Anterior uveitis:

Bilateral acute anterior uveitis was seen in preclinical toxicology studies. This is 
believed to be secondary to anti-drug antibody (ADA) immune complexes deposited 
in the eyes of the animals. No events of anterior uveitis were reported in study 
FP1039-001.

Optic neuritis, papilledema, and cerebral blindness have been reported in patients 
receiving standard recommended doses of cisplatin.


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
An ophthalmologic exam will be performed at screening and at Cycle 4 
(Section 7.3.7). If at any time the subject complains of photophobia, changes in 
vision, or eye pain; the ophthalmic examination finding are abnormal; or visual 
acuity has worsened by 3 lines or more since the start of the study the subject will be 
referred for a formal evaluation, including a slit-lamp examination and intraocular 
pressure, by a qualified ophthalmologist.
Wound healing:

Abnormal wound healing is a theoretical risk associated with inhibition of the FGF
signaling pathway. No events of abnormal wound healing have been reported 
previously. Subjects with non-healing wounds that, in the opinion of the investigator, 
would pose a significant medical risk to the subject should wound healing be further 
impaired, will be excluded from participation in this study. 

Interruption of therapy is recommended in subjects undergoing surgical procedures; 
treatment with GSK3052230 should be stopped at least 14 days prior to scheduled 
surgery and restarted only after complete healing has occurred and been documented 
in subject’s notes. 
Bowel perforation:

One subject developed fatal bowel perforation in Study FP1039-001.The subject’s 
history was notable for several risk factors for perforation.  However, GSK3052230 
may have anti-angiogenic activity that has previously been associated with a risk of 
bowel perforation, so subjects with conditions with an increased risk for bowel 
perforation are excluded from participation in this study.
Heart valve fibrosis:

Heart valve thickening due to fibrosis was noted at necropsy in 2 rats in a 4-week 
toxicology study. This finding was consistent with chronic persistent irritation and 
attributed to infusion catheter complications.

Subjects participating will undergo echocardiography at screening and Cycle 4 for 
evaluation of cardiac valve abnormalities and left ventricular ejection fraction 
(LVEF) changes (note, additional assessments may be obtained as clinically 
indicated or if the subject discontinues prior to Cycle 4). 
Peripheral Neuropathy 

One event of worsening bilateral leg neuropathy/muscle weakness was reported as a 
possibly related SAE in a subject with pre-existing neuropathy in Study FP1039-001.

Peripheral neuropathy is a potentially overlapping toxicity between GSK3052230, 
taxanes such as paclitaxel and docetaxel, and cisplatin.

Complete physical exam will be performed at screening. Also, disease-oriented 
physical examination will be performed on Day 1 of each cycle, Day 22 of the last 
cycle on treatment or 7 days after last visit off treatment, and 30 days after 
discontinuation of GSK3052230 therapy


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Hypothyroidism:

Slightly reduced weight of the thyroid gland was seen in preclinical toxicology 
studies. In study FP1039-001, 2 events of hypothyroidism/increased thyroid 
stimulating hormone (TSH) were reported. 

Subjects participating in clinical studies with GSK3052230 will be assessed for TSH 
at baseline and periodically during the study. If TSH is abnormal, additional thyroid 
assessments (total T3, total T4, free T4) along with appropriate clinical assessments 
are warranted.
Hematologic toxicity:

Two events of neutropenia (Grade 3 and grade 4) were reported in Study FP1039-001 
for an overall rate of 5.1%. Furthermore, paclitaxel, docetaxel, and cisplatin have 
known bone-marrow toxicity. 

All subjects in the study will have their blood counts monitored regularly, and 
supportive therapy including blood transfusions and growth factor support is 
encouraged (Section 9.1).
Nephrotoxicity:

Dose-related and cumulative renal insufficiency, including acute renal failure, is the 
major dose-limiting toxicity of cisplatin. Renal toxicity has been noted in 28% to 36% 
of patients treated with a single dose of 50 mg/m2. It is first noted during the second
week after a dose and is manifested by elevations in BUN and creatinine, serum uric 
acid and/or a decrease in creatinine clearance. Renal toxicity becomes more 
prolonged and severe with repeated courses of the drug. Renal function must return to 
normal before another dose of cisplatin can be given.

One patient with severe renal impairment (creatinine clearance 19 mL/min) who did 
not receive folic acid and vitamin B12 died of drug-related toxicity following 
administration of pemetrexed alone.
Ototoxicity:

Ototoxicity has been observed in up to 31% of patients treated with a single dose of 
cisplatin 50 mg/m2, and is manifested by tinnitus and/or hearing loss in the high 
frequency range (4000 to 8000 Hz). Decreased ability to hear normal conversational 
tones may occur. Deafness after the initial dose of cisplatin has been reported. 
Hearing loss can be unilateral or bilateral and tends to become more frequent and 
severe with repeated doses. Careful monitoring per standard of care should be 
performed.


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2.
OBJECTIVES AND ENDPOINTS
2.1.
Primary
Objectives
Endpoints
Primary
To characterize the safety and tolerability 
of GSK3052230 in combination with 
chemotherapy regimens.
Measurements used to evaluate safety 
and tolerability will include rate and 
severity of AEs, withdrawals due to AEs, 
dose interruptions and reductions, 
treatment duration, and DLTs as well as 
change from baseline for the following: 
physical examinations, vital signs,:12-lead 
ECGs, ECHO, clinical laboratory tests.
To determine the regimen of 
GSK3052230 in combination with 
chemotherapy for evaluation in future 
studies based on the maximum tolerated 
dose (or maximum feasible dose).
Maximum tolerated dose (MTD) or 
maximum feasible dose (MFD).
To assess the overall response rate 
(ORR) in each treatment arm.
Best response defined as complete or 
partial response, stable disease or 
progressive disease according to RECIST 
1.1 or modified RECIST (for MPM)
ORR defined as the proportion of subjects 
with investigator-assessed confirmed 
complete response or partial response per 
RECIST 1.1 or modified RECIST (for 
MPM)
2.2.
Secondary
Objectives
Endpoints
Secondary
To assess progression free survival 
(PFS) for each treatment arm. 
PFS is defined as the interval between first 
dose of GSK3052230 and the earliest date 
of disease progression or death due to 
any cause by investigator assessment per 
RECIST 1.1 or modified RECIST (for 
MPM)
Secondary
To characterize the population 
pharmacokinetics of GSK3052230 and 
identify important determinants of 
variability.
GSK3052230 population pharmacokinetic 
parameters such as clearance (CL) and 
volume of distribution (Vd), and relevant 
covariates which may influence exposure 
(e.g. age, weight, or disease related 
covariates).
Secondary
Assess improvement in Pulmonary 
Function Tests in Patients with MPM
Change from baseline in  Forced Vital 
Capacity (FVC) in patients with MPM


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2.3.
Exploratory
Objectives
Endpoints
Exploratory
To describe the kinetics of tumor growth 
in the presence of GSK3052230 for 
each treatment arm and investigate the
relationship between tumor growth 
kinetics and clinical activity. 
Tumor size over time, tumor growth rate 
constants, and time to tumor growth 
(TTG) predicted with the model 
parameters. Additional analysis will be 
performed utilizing volumetric analysis.
Exploratory
To identify biomarkers that may predict 
response or resistance.
Evaluate potential predictive/prognostic 
biomarkers (DNA, RNA, or protein) of 
response in circulation and/or in tumor.
Exploratory
To evaluate the pharmacodynamic 
response in circulation following 
treatment.
Changes in circulating biomarkers (eg, 
proteins) implicated in FGFR or disease 
biology signalling in pre and post dose 
blood samples. 
Exploratory
To explore the relationship between PK, 
pharmacodynamic response, and 
clinical endpoints.
Predicted/observed exposure (AUC), 
trough concentrations (C), or other PK 
endpoints as compared to 
pharmacodynamic and clinical endpoints.
Exploratory
To develop and validate an assay to 
measure  FGFR1 gene amplification 
status such as, but not limited to, a 
Fluorescence in situ hybridization 
(FISH) -based assay..
Association of FGFR1 gene amplification 
with clinical response to support the 
development of an investigation use only 
test (IUO) and potential companion 
diagnostic for subject selection.
Exploratory
To investigate additional measures of 
FGF signaling pathway deregulation as 
potential predictive biomarkers for 
GSK3052230 in tissue.
Identification and validation of alternative 
measures of FGF signaling pathway 
deregulation retrospectivelysuch as 
ligand or receptor overexpression for 
example but not limited to FGF2 or 
FGFR1 expression   FGF2 
overexpression) as predictive biomarkers 
for subject selection and potential 
development of a companion diagnostic.
Exploratory
To evaluate changes in patient reported 
outcomes
Change from baseline and association 
with ORR in observer and patient 
assessed components of the Lung 
Cancer Symptom Scale (LCSS) and 
LCSS-meso
Pharmacogenetics
To investigate the relationship between 
genetic variants in the host DNA and 
the pharmacokinetics of GSK3052230
and/or the relationship between genetic 
variants in the host DNA and the 
efficacy, safety and tolerability of 
GSK3052230.
Refer to Appendix 1. 


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3.
STUDY POPULATION
3.1.
Number of Subjects
Approximately 70 subjects will be enrolled in the study (minimum of 38 and up to 
approximately 120, alternative dosing cohorts could potentially add another 6 to ~ 40 
subjects). In addition to minimum and maximum sample sizes for each arm, sample sizes 
that would be expected under the null and alternative hypothesis rates are provided in 
Section 12.3.
3.2.
Subject Selection Criteria
Specific information regarding warnings, precautions, contraindications, AEs, and other 
pertinent information on the GSK study treatment or other study treatment(s) that may 
impact subject eligibility is provided in the Investigator Brochure [GlaxoSmithKline 
Document Number 2013N160379_00] and the individual product labels [Taxol PI, 2011], 
[Paraplatin PI, 2010], [Taxotere PI, 2010], [Alimta PI, 2004], [Platinol PI, 2010].
Deviations from inclusion/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.
3.2.1.
Inclusion Criteria
Subjects eligible for enrolment in the study must meet all of the following criteria:
1.
Signed written informed consent;
2.
Histologically or cytologically confirmed diagnosis:
Arms A and B: Stage IV or recurrent metastatic squamous NSCLC [TNM 
classification of malignant tumors, 7th edition, 2009; Edge, 2010] with FGFR1 gene 
amplification by central laboratory testing.
Arm C: recurrent after local therapy or unresectable malignant pleaural 
mesothelioma (MPM) with measurable lesions.

For specific arms the following requirements:
Arm A: Subjects who have received no prior therapy for Stage IIIB or Stage IV or 
recurrent metastatic disease. Note, to avoid any undue delay of initiating systemic 
chemotherapy for these subjects with newly diagnosed advanced or metastatic 
disease, it is allowed to initiate the first cycle of chemotherapy while eligibility for 
the study is still being determined, as long as the first dose of GSK3052230 is given 
no later than Cycle 2 Day 1 of chemotherapy. In addition, subjects with Stage IIIB or 
Stage IV disease and recurrence after previous NSCLC that has been treated with 
surgery and adjuvant chemotherapy or a radio-chemotherapy regimen with curative 
intent are eligible, provided 6 months has passed since this treatment ended[TNM 
classification of malignant tumors, 7th edition, 2009; Edge, 2010].


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Arm B: Subjects who have documented tumor progression (based on radiological 
imaging) or intolerability after receiving at least one prior line of platinum 
containing combination chemotherapy for Stage IIIB, Stage IV or recurrent 
metastatic disease [TNM classification of malignant tumors, 7th edition, 2009; Edge, 
2010].. Note: Prior treatment should not include docetaxel but may have included 
paclitaxel.
Arm C: Subjects who have received no prior systemic therapy for MPM.
3.
Availability of archival tumor tissue required for assessment of deregulated FGF 
pathway signaling eg, FGFR1 amplification or FGF2 or FGFR1 expression. If 
archival tissue is not available, a fresh biopsy is required. Please refer to Section 
7.7.1  
In Arms A and B, subjects will be prospectively screened for FGFR1 gene 
amplification using a FISH assay (note, local testing is permitted for pre-screening 
of subjects prior to central testing) for the dose expansion and the MTD/MFD 
cohorts only. For inclusion in this study, based on the central laboratory testing, 
FGFR1 gene amplification must meet one of the following criteria: a ratio of
FGFR1/CEN 8 of ≥2; or average number of FGFR1 signals per tumor nucleus of ≥6; 
or the percentage of tumor nuclei containing  ≥5 FGFR1 signals is ≥50%. 
In Arm C, FGF2 expression by IHC will be evaluated retrospectively in tissue 
samples by a central laboratory and is not a requirement for study entry.
4.
Measurable disease per RECIST version 1.1 (Arm A and B) and modified RECIST 
for Arm C.
5.
Male or female 18 years of age.
6.
Women of childbearing potential must have a negative serum pregnancy test within 
7 days of first dose of study treatment and agree to use effective contraception, as 
defined in Section 10, from 14 days prior to the first dose of study treatment, 
throughout the study, and for 6 months following the last dose of chemotherapy or 4 
weeks after the last dose of GSK3052230, whichever is latest.
7.
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 10.1.2 for 
at least 2 weeks prior to administration of the first dose of study treatment and for at 
least 6 months after the last dose of chemotherapy, to allow for clearance of any 
altered sperm.
8.
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 for Arms
A and C subjects and 0-2 for Arm B. 
9.
French subjects: In France, a subject will be eligible for inclusion in this study only 
if either affiliated to or a beneficiary of a social security category.
10. Must have adequate organ function as defined by the following baseline values:


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Table 1
Inclusion Criteria: Adequate Organ Function
SYSTEM
LABORATORY VALUES
Hematologic
ANC
1.5 x 109/L
Hemoglobin a
9 g/dL 
Platelets
100 x 109/L
Partial thromboplastin time (PTT)
≤ 1.25 x ULN.
Hepatic
Albumin
2.5 g/dL
Serum total bilirubin b
1.25 times ULN (for Arm B: ULN ) 
AST and ALT
2.5 times ULN (for Arm B: 1.5 times ULN)
Renal
Serum Creatinine
Or
Measured or Calculated Creatinine Clearance c
1.5 x ULN
Or
≥45 mL/min  (Arm A or B) ≥65 mL/min (Arm C)
Cardiac
Left ventricular ejection fraction
≥50%by ECHO
a. Subjects should meet criteria in the absence of hematopoietic growth factors or transfusions.
b. If the serum total bilirubin is elevated at screening but the direct bilirubin is ≤ULN then the subject may be allowed to 
enter study.
c. Calculated by the Cockcroft and Gault formula.
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.
3.2.2.
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.
For Arms A and C: Treatment with any FGFR inhibitor.
For Arm B: Treatment with any anti-cancer therapy (for biological anti-cancer 
therapies see criteria 2) during the preceding 4 weeks or within 4 half-lives of the 
therapy, whichever is longer.
2.
Receipt of any biological therapy within 6 weeks of the first dose of GSK3052230.
3.
Unresolved toxicity of National Cancer Institute Common Terminology Criteria for 
Adverse Events, version 4.03 (NCI CTCAE v4.03) [NCI, 2010] Grade 2 or higher 
from previous anti-cancer therapy, except alopecia
4.
Active malignancy other than the cancer under study. Subjects with a history of 
completely resected non-melanomatous skin carcinoma or successfully treated in situ 
carcinoma are eligible.
5.
Presence of uncontrolled infection.


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6.
Prior major surgery or trauma within 28 days before first dose of study drug.
7.
Presence of any non-healing wound, fracture, or ulcer.
8.
Any prohibited medication(s) as described in Section 9.2.
9.
Conditions likely to increase the potential for abdominal perforation or fistula 
formation, including but not limited to:

Luminal intestinal cancers or bulky abdominal disease.

Presence or history of abdominal fistula, gastrointestinal perforation, peptic 
ulcer disease or intra-abdominal abscess within the six months prior to the first 
dose of GSK3052230.

Other risk factors for perforation, such as acute diverticulitis, obstruction or 
previous abdominal or pelvic radiation.
10. Symptomatic leptomeningeal or brain metastases or spinal cord compression.
NOTE: Subjects previously treated for these conditions are eligible if they meet 
both of the criteria below:
(1) have had stable CNS disease for at least 4 weeks after local therapy as assessed 
by imaging (contrast enhanced magnetic resonance imaging (MRI) or computed 
tomography (CT)) prior to Day 1, and
(2) are asymptomatic and off corticosteroids, or are on stable dose of corticosteroids 
for at least 4 weeks prior to Day 1.
11. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to 
drugs chemically related to study drugs (GSK3052230, docetaxel, paclitaxel, 
carboplatin, pemetrexed, cisplatin) or their excipients that contraindicates their 
participation.
12. Known human immunodeficiency virus (HIV)-positive serology, acquired 
immunodeficiency syndrome (AIDS), or an AIDS-related illness.
13. Prior organ or allogeneic stem cell transplant.
14. The following cardiac abnormalities:

Corrected QT (QTc) interval 480 msecs

History of acute coronary syndromes (including unstable angina) within the past 
24 weeks

Coronary angioplasty, or stenting within the past 24 weeks

Class II, III, or IV heart failure as defined by the New York Heart Association 
(NYHA) functional classification system

Abnormal cardiac valve morphology (≥ Grade 2) documented by 
echocardiogram (subjects with Grade 1 abnormalities [i.e., mild 
regurgitation/stenosis] can be entered on study). 

History of known arrhythmias (except sinus arrhythmia and atrial fibrillation 
that is controlled) within the past 24 weeks


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15. Presence or history of hemoptysis (>½ teaspoon of red blood) 2 weeks prior to the 
first dose of GSK3052230.
16. Any serious and/or unstable pre-existing medical, psychiatric disorder or other 
conditions that could interfere with subject’s safety, obtaining informed consent or 
compliance to the study procedures.
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. Pregnant, lactating or actively breast feeding females.
19. French subjects: The French subject has participated in any study using an 
investigational study treatment(s) during the previous 30 days.
4.
INVESTIGATIONAL PLAN
4.1.
Discussion of Study Design
This will be a multi-arm, multicenter, non-randomized, parallel-group, uncontrolled, 
open-label Phase IB study designed to evaluate the safety, tolerability and preliminary 
activity of GSK3052230 in combination with paclitaxel + carboplatin (Arm A), in 
combination with docetaxel (Arm B), or in combination with pemetrexed + cisplatin 
(Arm C).
Figure 1
Study Schema
Pemetrexed/Cisplatin +
GSK3052230
3+3 design to determine
MTD  (MFD) in subjects with MPM
Arm C
Paclitaxel/Carboplatin +
GSK3052230
N=at least 12 and up to 30 sqNSCLC
Docetaxel+ GSK3052230
3+3 design to determine MTD (MFD) 
in subjects with sqNSCLC
Docetaxel+ GSK3052230
N=at least 14 and up to 30 sqNSCLC
Arm B
Paclitaxel/Carboplatin +
GSK3052230
3+3 design to determine
MTD  (MFD) in subjects with sqNSCLC
Arm A
Pemetrexed/Cisplatin +
GSK3052230
N=at least 12 and up to 30 MPM
Dose escalation will follow a 3+3 design as outlined in Section 4.2 for determination of 
MTD (or MFD).  A cohort expansion of at least 12 subjects will be treated at the MTD 
(or MFD) in each arm, with the option of expanding to a maximum of 30 subjects. 
Stopping rules based on anti-tumor activity were derived according to a predictive 
probability design for each arm of the study and are detailed in Section 4.2.1, Section 
4.2.2, and Section 4.2.3.


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GSK3052230 will be administered as a 30-minute intravenous (i.v.) infusion once a week 
(Day 1, Day 8, Day 15) of each 21-day cycle. Paclitaxel/carboplatin, docetaxel, and 
pemetrexed/cisplatin will be administered i.v. on Day 1 of each 21-day cycle. The 
number of cycles of paclitaxel/carboplatin will be limited to 4 to 6 cycles. Subjects may 
continue to receive docetaxel and pemetrexed/cisplatin until disease progression or as 
long as they are considered to derive benefit from treatment. Subjects on 
pemetrexed/cisplatin may have their cisplatin stopped after 4 cycles per local clinical 
standards. Subjects who discontinue chemotherapy for reasons other than disease 
progression, may continue to receive GSK3052230 as long as they are considered to 
derive benefit from the treatment according to the criteria in Section 6.3. After 
discontinuation of GSK3052230, subjects will return after approximately 30 days (see 
Time and Events Table Section 7.1) for a follow-up visit to collect safety assessments, 
after which they will be considered to have completed the study.
Blood samples for pharmacokinetic, pharmacogenetic, and translational research will be 
obtained at specified times during the study.  Efficacy will be assessed every 2 cycles 
during the first year and every 4 cycles thereafter.
All study treatments, including investigational product, will be referred to as ‘study 
treatment’ for ease of presentation throughout the protocol.  For EU regulatory purposes, 
the term ‘investigational product’ will only be used in Section 5 when describing the 
GSK3052230.
Protocol waivers or exemptions are not allowed.  Therefore, adherence to the study 
design requirements, including those specified in the Time and Events Table 
(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.
4.2.
GSK3052230 plus Chemotherapy
Dose escalation will follow a 3 + 3 dose-escalation procedure, described in Table 2. Dose 
limiting toxicities (DLTs) are based on any observed toxicity in the first 21 days of 
treatment (please see Section 4.2.4).  An additional (4th) subject is allowed in each cohort 
of 3 to ensure 3 evaluable subjects for determination of DLTs.  Evaluation of available 
safety data from at least 3 subjects who have completed a minimum of 21 days (1 cycle) 
is required prior to expanding a cohort or escalating to the next higher dose cohort.
Dose escalation will be explored in cohorts of 3 to 6 subjects to determine the MTD (or 
MFD), defined in Section 4.2.4.  The cohort may be expanded up to 9 subjects to further 
evaluate safety, pharmacokinetics and tolerability before dose escalation or reduction 
decision is determined. 


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Table 2
Dose Escalation 3+3 Design Process for Arms A, B
Number of subjects at given dose 
level with DLT
Action
0 out of 3 subjects
Proceed to next relevant dose-level or expand cohort to a total of 
6 evaluable subjects as appropriate
1 out of 3 subjects
Accrue 3 additional evaluable subjects at current dose level for a 
total of 6 evaluable subjects
1 out of 6 subjects
Proceed to next relevant dose-level or expand cohort to 9 as 
appropriate.
2 or more out of 3 or 6 subjects in a 
dosing cohort a
The MTD has been exceeded. Dose reduction in this Arm should 
be considered. 
Either evaluate an intermediate dose lower than current dose or 
expand a prior cohort. 
a. If 9 subjects in a cohort, then 3 or more out of 9
4.2.1.
Arm A
The starting dose (Dose Level 0) and escalation/de-escalation schema for GSK3052230 
in combination with paclitaxel + carboplatin is presented in Table 3.  Depending on 
emerging data, additional intermediate or lower dose-levels beyond those described may 
be explored.
Table 3
Combination Therapy: Arm A GSK3052230 + Paclitaxel + Carboplatin
Dose Level
Dose of GSK3052230
(Weekly)
Paclitaxel + Carboplatin a
(once every 21 days)
Dose Level -2
5 mg/kg
135 mg/m2 + AUC 4 
Dose Level -1
5 mg/kg
175 mg/m2 + AUC 5 
Starting Dose Level 0
5 mg/kg
200 mg/m2 + AUC 6 
Dose Level 1
10 mg/kg
200 mg/m2 + AUC 6 
Dose Level 2
20 mg/kg
200 mg/m2 + AUC 6 
a. Carboplatin dose based on Calvert’s formula.
A total of at least 12 subjects will be enrolled at the target dose to further evaluate safety 
and efficacy. After 12 subjects have been enrolled, the number of observed confirmed 
responses will guide further enrolment according to the stopping rules.  The futility 
boundaries (inclusive) for ORR for Arm A are 0/12, 1/14, 2/17, 3/20, 4/22, 5/24, 6/26, 
7/27, 8/28, 9/29, and 10/30 subjects and are shown in tabular format in Section 12.7. Up 
to 30 subjects will be enrolled in Arm A. All available data will be considered in making 
enrollment decisions.
Arm A: Screening procedure for subjects on chemotherapy
To avoid any undue delay in initiating systemic chemotherapy for subjects with newly 
diagnosed Stage IV or recurrent metastatic disease, the first cycle of chemotherapy may 
be initiated while determination of eligibility is being completed for the present study.  


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The first dose of GSK3052230 should be given no later than Cycle 2 Day 1 of 
chemotherapy.
Subjects who have started with the initial dose of systemic chemotherapy will have the 
following done:

Complete full screening procedures for FGF117360 as outlined in Section 7.1.

All treatment related toxicities (>Grade 2) should be resolved prior to starting 
GSK3052230.

Ensure documentation of all medical history (adverse events pre-baseline) in eCRF 
prior to start of treatment with GSK3052230.
4.2.2.
Arm B
The starting dose (Dose Level 0) and escalation/de-escalation schema for GSK3052230 
in combination with docetaxel is presented in Table 4.  Depending on emerging data, 
additional intermediate or lower dose-levels beyond those described may be explored.
Table 4
Combination Therapy: Arm B GSK3052230 + Docetaxel
Dose Level
Dose of GSK3052230
(weekly)
Docetaxel
(once every 21 days)
Dose Level -2
5 mg/kg
40 mg/m2
Dose Level -1
5 mg/kg
55 mg/m2
Starting Dose Level 0
5 mg/kg
75 mg/m2
Dose Level 1
10 mg/kg
75 mg/m2
Dose Level 2
20 mg/kg
75 mg/m2
A total of at least 14 subjects will be enrolled at the target dose to further evaluate safety 
and efficacy. After 14 subjects have been enrolled, the number of observed confirmed 
responses will guide further enrolment according to the stopping rules. The futility 
boundaries (inclusive) for ORR for Arm B are 0/14, 1/22, 2/26, 3/28, 4/29, and 5/30 
subjects and are shown in tabular format in Section 12.7 Up to 30 subjects will be 
enrolled in Arm B. All available data will be considered in making enrollment decisions.
4.2.3.
Arm C
Arm C will open for enrollment subsequent to Amendment 3. The starting dose of 
GSK3052230 (Dose Level 0) in Arm C will be 10 mg/kg, as long as the 5 mg/kg dose in 
combination with chemotherapy in Arm A did not exceed the MTD. Otherwise, the 
starting dose level in Arm C will be Dose Level -1. Dose levels and escalation/de-
escalation schema for GSK3052230 in combination with pemetrexed and cisplatin is 
presented in Table 5.  Depending on emerging data, additional intermediate or lower 
dose-levels beyond those described may be explored.


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Table 5
Combination Therapy: Arm C GSK3052230 + Pemetrexed + Cisplatin
Dose Level
Dose of GSK3052230
(Weekly)
Pemetrexed + Cisplatin
(once every 21 days)
Dose Level -2
5 mg/kg
400 mg/m2 + 60 mg/m2
Dose Level -1
5 mg/kg
500 mg/m2 + 75 mg/m2
Starting Dose Level 0
10 mg/kg
500 mg/m2 + 75 mg/m2
Dose Level 1
20 mg/kg
500 mg/m2 + 75 mg/m2
A total of at least 12 subjects will be enrolled at the target dose to further evaluate safety 
and efficacy. After 12 subjects have been enrolled, the number of observed confirmed 
responses will guide further enrolment according to the stopping rules. The futility 
boundaries (inclusive) for ORR for Arm C are 2/12, 3/14, 4/16, 5/18, 6/20, 7/21, 8/23, 
9/24, 10/25, 11/26, 12/27, 13/28, 14/29 and 15/30 subjects and are shown in tabular 
format in Section 12.7 Up to 30 subjects will be enrolled in Arm C. All available data 
will be considered in making enrollment decisions.
4.2.4.
Dose-Limiting Toxicity
DLT will be defined as toxicities due to GSK3052230 or due to the combination of 
GSK3052230 with chemotherapy within Cycle 1 (first 21 days of period on study) that 
are unlikely to be due to another cause, such as the known effects of cytotoxics 
chemotherapy alone, disease progression, or accident, according to the criteria below: 

Grade 3 or 4 clinically significant non-hematological toxicity (excluding: Grade 3 
nausea/vomiting or Grade 3 diarrhea that responds to optimal medical care within 3 
days; Grade 3 infusion reactions that can be medically managed without the use of 
systemic pressors and allow completion of infusion.)

Grade 4 neutropenia lasting more than 7 days

Grade 4 febrile neutropenia

Grade 4 thrombocytopenia (of any duration)

Grade 4 clinically significant laboratory abnormalities with duration greater than 
48hrs

Treatment delay of 14 days or greater due to unresolved drug-related toxicity.

Any grade 2 toxicity which in the judgement of the investigator and GSK medical 
monitor is considered a DLT
Clinically significant toxicities that persist or occur beyond Cycle 1 that the investigator 
and GSK medical monitor consider dose-limiting may also be designated a DLT for the 
purpose of establishing MTD.
4.2.5.
Maximum Tolerated Dose
The MTD for the combination regimens will be defined as the highest dose level tested at 
which < 33% of subjects experience a DLT.  Up to 30 subjects for each regimen may be 
treated at the MTD or at the highest dose evaluated if the MTD is not reached (this dose 


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will be described as the MFD).  The dose recommended for Phase 2 studies will take into 
consideration toxicity and tolerability from all dose levels and treatment cycles.
4.2.6.
Intra-Subject Dose Escalation or Dose De-escalation
Intra-subject dose escalations may be considered on a case-by-case basis, provided that
the higher dose level cohort from the 3+3 phase of the study has been cleared without a 
DLT, and after review of all safety data and approval by a GSK Medical Study Physician
and discussion with the investigator.  The subject on a lower dose level may be increased 
up to the highest dose level tested.  In this case, the subject may begin dosing at the 
higher dose level as it will have already been demonstrated to be tolerable and monitoring 
will be performed as described in the protocol. For example, a subject who enrolled at a 
dose level below the MTD (or MFD) and may be eligible for dose increases if the 
investigator believes the subject could benefit.
4.2.6.1.
Alternative Dosing and Schedule Cohorts
Additional doses and schedules may be explored based on emerging pharmacokinetic and 
safety data. Alterations may be made to the schedule of PK/PD sampling based on 
emerging PK data.  
The sample size of the “alterative dosing and schedule cohorts” will be based on the 3 + 3 
design with potential to expand to up to 30 subjects in this regimen.  
The rationale for exploring this alterative dosing and/or schedule is to expand on the 
safety, tolerability and preliminary efficacy.
4.3.
Rationale
4.3.1.
Rationale for Evaluation of GSK3052230 in Chemotherapy 
Combinations
FGFR1 amplification has been associated with significantly shorter disease free and 
overall survival in NSCLC [Kim, 2013; Heist, 2012].  Carboplatin and paclitaxel can be 
used in first line therapy of NSCLC and docetaxel is a standard second line agent.  
Pemetrexed and cisplatin is the standard first line therapy for mesothelioma. Additive 
antitumor effect was demonstrated in tumor xenograft models treated with the 
combinations of GSK 3052230 and chemotherapy including paclitaxel and carboplatin as 
well as docetaxel. Malignant pleural mesothelioma (MPM) is a tumor type where FGF2 
ligand overexpression has been observed in a high percentage of primary specimens and 
where GSK3052230 preclinical efficacy has been observed in xenograft models. Based 
on the clinical and preclinical data, the combination of GSK3052230 with chemotherapy 
will be investigated in patients with NSCLC or with mesothelioma.
4.3.2.
Rationale for Dose of GSK3052230
The highest dose tested in the Phase 1 study FP1039-001 was 20 mg/kg. A maximum 
tolerated dose was not determined in the Phase 1 trial; the 20 mg/kg dose was determined 
to be safe and was declared the maximum feasible dose.  This dose was not associated 


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with toxicity in rat and dog toxicity studies of 13 weeks duration.  A 10 to 20 mg/kg dose 
is estimated to be the dose range needed to achieve clinical activity based on 
exposure/efficacy relationships in preclinical xenograft models.  In these efficacy models, 
trough plasma levels of GSK3052230 associated with tumor growth inhibition of 54% to 
69% ranged from approximately 0.2 to 23.3 µg/mL for preclinical doses of 1.3 mg/kg to 
12.8 mg/kg.  Levels within the upper part or above that range were achieved at clinical 
doses of GSK3052230 of 10 and 20 mg/kg.  Weekly dosing is required to maintain levels 
within the expected range for activity, based on PK analysis from the completed Phase 1 
study (GlaxoSmithKline Document Number 2013N160379_00).
4.3.3.
Rationale for Endpoints
Safety, tolerability and efficacy (ORR) are being assessed to address the primary 
objectives of the study. The safety assessments along with the PK will be important for 
determining the MTD (or MFD). The efficacy and pharmacodynamic assessments will 
further support the recommended phase II dose and expand the understanding regarding 
mechanism of action. Response rate stopping rules were determined separately for Arms 
A, B and C. In each case, the null hypothesis rate was determined using available 
literature and the alternative hypothesis rate constituted an improvement in therapy. 
Details of null and alternative hypothesis rates are provided in Section 12.3. Symptom 
assessments as measured by the LCSS and LCSS-meso were added to increase the 
understanding of the patient experience and perceptions.
4.4.
Study Treatment Assignment
Subjects will be identified by a unique subject number that will remain consistent for the 
duration of the study.  Upon completion of all the required screening assessments, 
eligible subjects will be registered into RAMOS (Registration and Medication Ordering 
System).
4.5.
Dosage and Administration of Study Treatments
4.5.1.
GSK3052230
Subjects in all arms will receive GSK3052230 administered as a 30-minute infusion once 
a week (Day 1, Day 8, and Day 15) of each 21-day cycle at the dosages specified in 
Section 4.2. Following infusion of GSK3052230, subjects should be observed for 1 hour 
prior to infusion of chemotherapeutic agents.  If infusion reactions are noted, subjects 
should be treated with antiemetics, steroids, or antihistamines at the discretion of the 
investigator and premedication according to institutional standards before further 
infusions of GSK3052230 should be considered.  Dose modifications should follow the 
guidelines in Section 4.7.4. Start and stop times of all infusions must be recorded.
4.5.1.1.
Study treatments: Alternative Dosing and Schedule cohorts
Subjects in these expansion cohorts will be dosed based on the pharmacokinetic and 
safety data from the ongoing study.  This will be determined at FGF117360 Study 
Investigator meetings (example: dose escalation meeting) and the minutes and 


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agreements would be provided to IRB/Ethics prior to dosing in this “Alternative Dosing 
and Schedule” Cohorts.
4.5.2.
Paclitaxel + Carboplatin
Subjects in Arm A will receive pre-treatment for paclitaxel and carboplatin according to 
institutional standards. Paclitaxel according to the dose level being investigated as 
described in Table 3 will be administered intravenously over 3 hours (or according to 
local clinical standards) in a constant rate infusion on Day 1 of each 21 day treatment 
cycle immediately followed by i.v. carboplatin at a dose calculated for a target maximum 
AUC of AUC=6 as a 30 to 60 minute constant rate infusion (or according to local clinical 
standards).  A total of 4 to 6 cycles of paclitaxel/carboplatin will be administered per 
local clinical practice.
Carboplatin will be dosed using the Calvert Formula [Calvert, 1989]. This approach uses 
a mathematical formula, which is based on a subject’s pre-existing renal function or renal 
function and desired platelet nadir. Renal excretion is the major route of elimination for 
carboplatin. The formula calculates the dose based on a subject’s glomerular filtration 
rate (GFR in mL/min) as measured by Cr-EDTA clearance and carboplatin target area 
under the concentration versus time curve (AUC in mg/ml•min). With the Calvert 
formula, the total dose of carboplatin is expressed in mg, NOT mg/m2:
Total Carboplatin Dose (mg) = (target AUC) x (GFR1 + 25)
1NOTE: The GFR used in the above Calvert formula to calculate AUC-based 
carboplatin dosing should not exceed 125 mL/min. Therefore, the maximum 
carboplatin dose (mg) equals the target AUC (mg/ml•min) multiplied by 150 mL/min.
Maximum Carboplatin Dose (mg) = target AUC (mg/ml•min) x (150 mL/min)
The maximum dose is based on a GFR estimate that is capped at 125 mL/min for patients 
with normal renal function. No higher estimated GFR values should be used.
For a target AUC = 6, the maximum dose is 6 x 150 = 900 mg
For a target AUC = 5, the maximum dose is 5 x 150 = 750 mg
For a target AUC = 4, the maximum dose is 4 x 150 = 600 mg
The maximum target AUC explored in any cohort in this study is AUC=6. Therefore, 
using the Calvert formula above, the maximum carboplatin dose in mg should not 
exceed 900 mg.
The Cockroft-Gault formula (see Appendix 3) can be used to calculate the creatinine 
clearance (CLCR), which can be substituted for the GFR in the Calvert formula.
Additional information, packaging, preparation and administration information can be 
found in the prescribing information for carboplatin [Paraplatin USPI, 2010]. 
Dose modifications should follow the guidelines in Section 4.7. Start and stop times of all 
infusions must be recorded.


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4.5.3.
Docetaxel
Subjects in Arm B will receive pre-treatment for docetaxel according to institutional 
standards. Docetaxel will be administered according to the dose level being explored as 
described in Table 4 as an i.v. infusion over 1 hour (or according to local clinical 
standards) on Day 1 of each 21 day cycle.  The subject is treated until progression or until 
the subject has been determined to have received maximum benefit.
For additional formulation, packaging, preparation and administration information, please 
refer to the current product labeling (e.g. US package insert or product monograph) for 
country specific docetaxel dosing guidelines.
Dose modifications should follow the guidelines in Section 4.7. Start and stop times of all 
infusions must be recorded.
4.5.4.
Pemetrexed and Cisplatin
Subjects in Arm C will receive pre-treatment for pemetrexed and cisplatin according to 
institutional standards. Pemetrexed according to the dose level being investigated (Table 
5) will be administered intravenously over 10 minutes (or according to local clinical 
standards) on Day 1 of each 21 day treatment cycle followed 30 minutes later by i.v. 
cisplatin infused over 2 hours.
Subjects will be hydrated and pre-medicated with folic acid and vitamin B12 supplements 
in order to reduce the incidence and severity of hematologic and gastrointestinal toxicities 
as well as cutaneous hypersensitivity reactions as per institutional guidelines.  
Recommendations for pre-medication are as follows:

1-2 liters of fluid infused for 8-12 hours prior to cisplatin dose (or hydration per local 
standard)

350-1000 g folic acid, once daily, by mouth for seven days preceding the first dose 
of pemetrexed, during treatment, and for 21 days following the last dose of 
pemetrexed

1000 g vitamin B12 by intramuscular injection in the week preceding the first dose 
of pemetrexed and every three cycles thereafter (subsequent vitamin B12 injections 
may be given on the same day as pemetrexed)

4 mg dexamethasone (or equivalent), twice daily, by mouth the day before, the day 
of, and the day after pemetrexed administration   
Additional information can be found in the prescribing information for pemetrexed 
[Alimta Package Insert, 2004] and cisplatin [Platinol, 2010]..  


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4.6.
Safety Management Guidelines
4.6.1.
Liver Chemistry Stopping Criteria
Specific liver dose modification and discontinue guidance for docetaxel is presented in 
Table 8 (see Section 4.7.3). For subjects who are not being treated with docetaxel, please 
follow the guidelines below.
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 times upper limit of normal (ULN) and bilirubin 
2 times ULN (or ALT 3 times ULN and international normalization ratio 
[INR] >1.5)
NOTE: Serum bilirubin fractionation should be performed if testing is available. If 
fractionation is unavailable, urinary bilirubin is to be measured via dipstick (a 
measurement of direct bilirubin, which would suggest liver injury).
2.
ALT 5 times ULN.
3.
ALT 3 times 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 times ULN persists for 4 weeks.
5.
ALT 3 times ULN and cannot be monitored weekly for 4 weeks.
Subjects with ALT 3 times ULN and <5 times ULN and bilirubin <2 times 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.
4.6.1.1.
Liver Chemistry Follow-up Procedures
Refer to the diagram in Appendix 5 for a visual presentation of the procedures listed 
below.
The procedures listed below are to be followed if a subject meets the liver chemistry 
stopping criteria defined in Section 4.6.1:

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.


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
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 if testing is available. If fractionation is unavailable, urinary 
bilirubin is to be measured via dipstick (a measurement of direct bilirubin, which 
would suggest liver injury).

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

Blood sample for PK analysis, obtained within 2 weeks of last dose. 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 a PK sample cannot be 
collected in the time period indicated above, do not obtain a PK sample.
Instructions for sample handling and shipping are included in the SPM. A subject 
may be requested to provide 2 samples for PK analysis (4mL sample per compound) 


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if the samples are taken less than 2 days after the last dose of paclitaxel (Arm A) or 
docetaxel (Arm B).

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.
4.6.2.
QTc Stopping Criteria
If a subject meets the corrected QT (QTc)1 interval duration criteria below following 
manual over-read of the ECG, 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) with 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(s) withheld.
If the QTc prolongation resolves to Grade 1 or baseline, the subject may be re-started on 
the study treatment(s) if the investigator and GSK Medical Monitor agree that the subject 
will benefit from further treatment. Dose reduction should be considered if the signs or 
symptoms are indicative of a proarrhythmic potential.
For subjects recruited in France or the UK, please refer to Appendix 7 for the country 
specific QTc stopping criteria.


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4.6.3.
Left Ventricular Ejection Fraction (LVEF) and Valvular Toxicity 
Stopping Criteria
4.6.3.1.
LVEF Stopping Criteria
Echocardiography must be performed at Screening and at Cycle 4 visit as outlined in the 
Time and Events Table (Section 7.1). Subjects who have an asymptomatic, absolute 
decrease of >10% in left ventricular ejection fraction (LVEF) compared with baseline and
the ejection fraction is below the institution’s lower limit of normal (LLN) should 
temporarily discontinue GSK3052230 and have a repeat evaluation of LVEF within 1 
week. Echocardiogram (ECHO) should be repeated every 1 to 2 weeks for 4 weeks or 
until LVEF recovery to above institutional LLN and within 10% of baseline.

If the LVEF recovers (defined as LLN 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 
GSK3052230 at a reduced dose. For such subjects, monitoring of LVEF will be 
performed 3 weeks after rechallenge, and every 3 weeks thereafter for 6 weeks 
and then per protocol.

If repeat LVEF does not recover within 4 weeks, treatment with GSK3052230
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 GSK3052230.  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 >10% decrease in LVEF from baseline and whose cardiac ejection fraction is 
<institutional LLN may be required by GSK for review.  Additionally, the decrease in 
LVEF is to be reported as an SAE. Instructions for submitting qualifying ECHOs may be 
found in the SPM.
4.6.3.2.
Cardiac Valve Toxicity Stopping Criteria
Subjects who have 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 
4.03) should temporarily discontinue GSK3052230 and have a repeat evaluation by 
ECHO within 1 week.  Echocardiogram 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 treatment cycle, after 
consultation and approval of the GSK Medical Monitor, the subject may be 
restarted on GSK3052230 at a reduced dose(s).  For such subjects, monitoring of 
the valve via ECHO will then be performed 3 weeks after rechallenge, as 
clinically appropriate.


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
If repeat ECHO does not reveal valve recovery to baseline within a treatment 
cycle, then the subject should permanently discontinue GSK3052230.  The valve 
should continue to be monitored via ECHO every 3 weeks after rechallenge, as 
clinically appropriate, 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 
GSK3052230.  Valvular toxicity should continue to be monitored every 3 weeks, as 
clinically appropriate, until resolution. 
ECHO must be performed at baseline and at Cycle 4.  Copies of all ECHO(s) and 
cardiology consultations performed on subjects who experience valvular toxicity may be 
required by GSK for review.  Additionally, the valvular toxicity is to be reported as an 
SAE. Instructions for submitting qualifying ECHOs are provided in the SPM.
4.6.4.
Management of Diarrhea
Diarrhea was reported in 44% of subjects participating in Study FP1039-001. The 
majority of these events were CTC grade 1 (88%) and no events of severe diarrhea were 
reported.  A baseline assessment of stool pattern is recommended in order to establish 
potential treatment emerging changes. Subjects should be instructed to immediately 
notify their physician/healthcare provider at onset of diarrhea and prompt investigation of 
potential causes should be initiated.  When infectious causes have been excluded, anti-
diarrheals (e.g. loperamide) should be considered.  For recommended dose modifications, 
see Section 4.7. 
4.6.5.
Management of Fluid Retention
Fluid retention should be graded as outlined in Table 6. No dose reduction is planned for 
fluid retention.  Patients developing new onset or symptomatic edema or other signs of 
increasing fluid retention should be treated with oral diuretics. Regimens found to be 
effective in the management of fluid retention due to docetaxel are listed below. Diuretic 
therapy may be initiated in the order listed at the discretion of the investigator: 

Spironolactone 50 mg by mouth (PO), once to three times daily. 

Furosemide 40 mg PO daily if not responsive to spironolactone. 
Potassium supplementation may be given as needed. 

If, after a trial of > 2 weeks, this is ineffective, treat with furosemide 20 mg PO daily 
plus metolazone 2.5 mg PO daily with potassium supplementation as needed. 
Further therapy following fluid retention should be customized depending upon the 
clinical situation.


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Table 6
Grading and Management of Fluid Retention
Severity Grading
Edema a
Effusion a
Mild (1)
Asymptomatic
Asymptomatic
Moderate (2)
Symptomatic
Symptomatic – intervention may be 
required
Severe (3)
Symptomatic – discontinue study 
drugs
Symptomatic – intervention required
a. Report the highest grade.
4.7.
Dose Modifications
The severity of adverse events (AEs) will be graded utilizing the National Cancer 
Institute- Common Terminology Criteria for Adverse Events (NCI-CTCAE), 
version 4.03. Guidelines for dose modifications and interruptions for management of 
common toxicities associated with the study treatment(s) are provided in this section.  
These include general guidelines based on the severity (CTCAE grade) of adverse events 
for GSK3052230 and key recommendations provided in the package insert for paclitaxel, 
carboplatin, and docetaxel [Taxol PI, 2011], [Paraplatin PI, 2010], [Taxotere PI, 2010].
4.7.1.
Dose Delays
Chemotherapy administration in all arms may be reduced or delayed for toxicity, or in the 
interest of subject safety per investigator discretion.  Requirement for more than 2 dose 
reductions will result in permanent discontinuation of chemotherapy.  If chemotherapy is 
discontinued due to toxicity, subjects may continue to receive GSK3052230 (Section 
6.3).
4.7.2.
Hematologic Toxicity Related to Chemotherapy
Guidelines for management of hematologic toxicity attributed to chemotherapy are given 
in Table 7. For severe cytopenias (grade 4), frequent follow-up of hematology should be 
performed (at least every 3 days until improved to at least Grade 3) and supportive 
therapy including G-CSF (per ASCO guidelines) is encouraged.  These are recommended 
reductions. Local guidelines for dose reductions may vary.  Dose reductions that differ 
from the following table should be discussed with the GSK Study Physician


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Table 7
Chemotherapy Dose Delay and Modifications for Hematologic 
Toxicity
Hematologic Toxicity
Modification Instructions
Absolute Neutrophil 
Count (ANC) Nadir
Platelets Nadir
≥500 to <1500 mm3 
(or <500/mm3 for <7 days 
and no neutropenic fever)
AND/OR
≥75,000 to <100,000/mm3
Withhold chemotherapy until ANC 
≥1500/mm3 and
Platelets ≥ 100,000/mm3
Restart treatment with no dose reductions
If treatment must be held for more than 2 
weeks, discuss potential retreatment or 
discontinuation with GSK Study Physician
<500/mm3
for ≥7 days and no 
neutropenic fever
OR
Neutropenic fever
AND/OR
<75,000/mm3
Withhold chemotherapy until ANC 
≥1500/mm3 and
Platelets ≥ 100,000/mm3
Arm A: Restart combination chemotherapy at 
dose levels reduced by 1 level for both agents 
according to Table 3. 
Arm B: Restart docetaxel reduced by 1 level 
according to Table 4
Arm C: Restart combination chemotherapy 
reduced by 1 level for the chemotherapy dose 
according to Table 5
Note, 2 dose reductions are allowed in case 
of recurring toxicity. 
If neutropenic fever occurs prophylactic G-
CSFs should be used with further 
chemotherapy treatment.
4.7.3.
Non-hematologic Toxicity Related to Chemotherapy
Guidelines for management of non-hematologic toxicity attributed to chemotherapy are 
given in Table 8.


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Table 8
Chemotherapy Dose Delay and Modifications for Non-hematologic 
Toxicity
Adverse Event
Action
Non-hematological, Grade 1 or 2
Continue chemotherapy.
Non-hematological, drug-related 
Grade 3 or 4 (except alopecia)
Hold chemotherapy until recovery to Grade ≤1.
Arm A: Restart at dose levels reduced by 1 level for both agents 
according to Table 3.
Arm B: Restart docetaxel reduced by 1 level according to Table 4
Arm C: Restart combination chemotherapy reduced by 1 level for 
the chemotherapy dose according to Table 5
Exceptions
Grade 3 or 4 hypersensitivity 
reactions
For Grade 3 hypersensitivity/infusion reactions that can be 
medically managed without the use of systemic pressors and allow 
completion of infusion, subjects are allowed to continue treatment 
at current dose with appropriate hypersensitivity prophylaxis.
Grade 4: discontinue study treatment
Grade 2 neurotoxicity
Arm C: Withhold study treatment until recovery to Grade 1; then 
resume treatment with cisplatin reduced by 50% of previous dose
Grade 3 or 4 Neurotoxicity 
Withhold study treatment until recovery to Grade 1; then resume 
treatment at dose reduced by 2 levels according to Table 3 (Arm A) 
or Table 4 (Arm B). Permanently discontinue chemotherapy in Arm 
C. If treatment delay is more than 2 weeks, re-initiation of treatment 
should be agreed with the GSK study physician.
Severe or cumulative cutaneous 
reaction (any Grades)
Hold until ≤Grade 1 or to baseline and restart with reduction in 
dose by 1 level according to Table 3 (Arm A) or Table 4 (Arm B).
AST/ALT >1.5 X ULN and
ALP >2.5 X ULNa
Arm B: Hold docetaxel. Monitor liver chemistries weekly. When 
recovered, docetaxel may be restarted reduced by 1 level 
according to Table 4. Also consult Section 4.6.1 for actions with 
GSK3052230
Bilirubin >ULN
Arm B: Hold docetaxel. Monitor liver chemistries weekly. When 
recovered, docetaxel may be restarted reduced by 1 level 
according to Table 4. Also consult Section 4.6.1for actions with 
GSK3052230
2.5x ULN< AST/ALT< 5xULN and 
1 X ULN< bilirubin  < 1.25 X ULN a
Arm A: At time of event, if the subject is dosing >175 mg/m2 of 
paclitaxel then dose reduce to 175 mg/m2; if the subject is currently 
at 175 mg/m2  then maintain the current dose level (remain at 175 
mg/m2.). Also consult Section 4.6.1 for actions with GSK3052230
2.5x ULN< AST/ALT< 5xULN and
bilirubin 1.26-2.0 X ULN a
Arm A: Reduce paclitaxel to 135 mg/m2 (or dose level below if 
already treated at this level). Also consult Section 4.6.1 for actions 
with GSK3052230
2.5x ULN< AST/ALT< 3xULN and
bilirubin 2.01-5.0 X ULN a
Arm A; Reduce paclitaxel to 90 mg/m2, If this is the second dose 
reduction required for liver toxicity, discontinue treatment. Also 
consult Section 4.6.1 for actions with GSK3052230
AST/ALT> 3 X ULN and
bilirubin 2.01-5.0 X ULN a
Arm A: This requires discontinuation of GSK3052230 and, hence, 
discontinuation from study after appropriate safety follow up.
Mucositis, Grade 3 or 4
Arm C: Reduce pemetrexed only by 50% of previous dose
Serum creatinine >1.5 mg/100mL or 
BUN >25mg/100mL
Arm C: Hold chemotherapy until serum creatinine <1.5 mg/100mL 
or BUN <25mg/100mL
Creatinine clearance <45 mL/min
Arm C: Hold chemotherapy until creatinine clearance ≥45 mL/min
a. Day 1 value to be used in determining elevation. Note that dose reductions for liver toxicity are permanent. Liver 
chemistry following-up procedures see Section 4.6.1.1.


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4.7.4.
GSK3052230 Dose Modifications
For toxicities at least possibly related to GSK3052230, dosing may be interrupted or 
delayed up to 14 days.  Approval from the GSK Study Physician is required to restart a 
dose after 14 days of dose interruption. 
If necessary, 5 mg will be the minimum dose level.  Following a dose reduction and 
resolution of toxicity to baseline levels, individual subjects may be re-escalated to a 
higher dose level with the approval of the GSK Study Physician.
Guidelines for dose modifications are outlined in Table 9.
Table 9
GSK3052230 Dose Modification Guidelines
Grade
Action
Grade 1 drug related event
No delay or modification
Grade 2 drug related event
May hold until reduced to Grade 1 or baseline at the discretion of the 
investigator, no dose reduction.
Grade 3 or higher drug related 
event (except Grade 3 nausea 
that resolves with clinical 
intervention)
Hold until Grade 1 or baseline, dose reduce 50%
If the toxicity is potentially related to both GSK3052230 and chemotherapy as given in
all arms, please refer to dose modification for chemotherapy in Section 4.7.2 and Section 
4.7.3 for potential dose reduction of both study treatments.
Subjects who experience a toxicity related to GSK3052230 that precludes further 
treatment with GSK3052230 will be withdrawn from the study treatment.
4.7.4.1.
GSK3052230 Dose Modifications regarding infusion related reactions
Subjects should be closely monitored for GSK3052230 infusion-related reactions. All 
subjects who have experienced an infusion reaction due to GSK3052230 (and not 
chemotherapy) should have GSK3052230 infused over 60 minutes instead of 30 minutes 
and pre-treated with appropriate local instituational pre-treatment guidelines (example: 
medications such as steroids, antihistamines, acetaminophen, H-2 antagonists, and 
antiemetics, according to local pre-treatment guidelines). If the subject continues to have 
a reaction on re-challenge, the infusion of GSK3052230 may be prolonged to 90 minutes. 
Epinephrine for subcutaneous injection, diphenhydramine for IV injection, and any other 
medications and resuscitation equipment for the emergency management of anaphylactic 
reactions should be quickly available during subject infusions.


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5.
INVESTIGATIONAL PRODUCT
The term ‘study treatment’ is used throughout the protocol to describe any combination 
of investigational product(s) (IP) received by the subject as per the protocol design. Study 
treatment may therefore refer to the individual study treatment or the combination of 
those study treatments.
Refer to the SPM (the FGF117360 Pharmacy Manual) for additional details on 
investigational product procedures.
5.1.
Description of Investigational Products
5.1.1.
GSK3052230
Product name :
GSK3052230, 12.8 mg/mL
Formulation description:
The product is formulated in 0.94 mg/mL sodium phosphate monobasic, 
1.9 mg/mL sodium phosphate dibasic, 8.8 mg/mL sodium chloride, 0.2 
mg/mL polysorbate 80, pH 7.0 at a GSK3052230 (HGS1036) 
concentration of 12.8 mg/mL. GSK3052230 contains no preservative.
Dosage form:
Solution for infusion
Unit dose strength(s)/Dose 
Level(s):
20 mg/kg
15 mg/kg
10 mg/kg
5 mg/kg
Physical Description: 
The drug product is a clear to opalescent, colorless to pale yellow 
solution that may contain small amounts of translucent to white 
proteinaceous particles.
Route/
Administration/ Duration:
Intravenous infusion once weekly (Day 1, Day 8, Day 15) in each 21-
day cycle administered using a 0.2 μm in-line filter
Dosing instructions:
Administer as a 30 minute infusion
Manufacturer:
GSK
GSK3052230 will be provided to sites by GSK. GSK3052230 is supplied in a sterile 
25 mL glass vial. Each vial is intended for single use. The deliverable volume per vial is 
20 mL. The contents of the label will be in accordance with all applicable regulatory 
requirements.
5.1.2.
Chemotherapeutic Agents
Paclitaxel, carboplatin, docetaxel, pemetrexed, and cisplatin will be sourced locally from 
commercial stock, except in countries where Regulatory Authorities mandate that the 
Sponsor must supply all non-investigational product (IPs) required for study 
participation. Investigators are responsible for ensuring that subjects receive supplies of 
paclitaxel, carboplatin, docetaxel, pemetrexed, and cisplatin for the entire duration of the 
study, as appropriate.  The contents of the label will be in accordance with all applicable 
regulatory requirements.


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5.2.
Preparation/Handling/Storage of GSK3052230
Preparation
Using aseptic techniques, GSK3052230 will be diluted in a 250 mL (nominal volume) 
i.v. bag containing either 5% dextrose solution or normal saline. GSK3052230 is stable 
after dilution in 5% dextrose solution or normal saline for up to 8 hours at ambient 
temperature (~25ºC). GSK3052230 infusion must be completed within 8 hours of the 
dilution. Please refer to SPM for recommended IV supplies.
Handling
Under normal conditions of handling and administration, 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.
Take adequate precautions to avoid direct eye or skin contact and the generation of 
aerosols or mists.
In the case of unintentional occupational exposure notify the study monitor, the GSK 
Medical Monitor and/or the study manager.
Refer to the SPM (the FGF117360 Pharmacy Manual) for detailed procedures for the 
disposal and/or return of unused study treatment(s).
Storage
Access to and administration of the GSK3052230 will be limited to the investigator and 
authorized site staff. GSK3052230 must be dispensed or administered only to subjects 
enrolled in the study and in accordance with the protocol. Refer to the SPM (the 
FGF117360 Pharmacy Manual) for storage conditions.
5.3.
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 IP 
dispensed and/or administered to study subjects, and the amount received from and 
returned to GSK, when applicable.  Product accountability records must be maintained 
throughout the course of the study.  Refer to the SPM (the FGF117360 Pharmacy 
Manual) for further detailed instructions on product accountability.
5.4.
Treatment Compliance
GSK3052230 and chemotherapy will be intravenously administered to subjects at the 
study site. Administration will be documented in the source documents and reported in 
the eCRF.


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5.5.
Treatment of Study Treatment Overdose
In the event of an overdose (defined as administration of more than the protocol-specified 
dose) of GSK3052230, 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 GSK3052230 can no longer be 
detected systemically (at least 14 days)

obtain a plasma sample for PK analysis 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.
In the event of an overdose of chemotherapy agents, please consult product label as well 
as following the above procedures.
6.
COMPLETION OR WITHDRAWAL OF SUBJECTS
6.1.
Screen Failures
Data for screen failures will be collected in source documentation at the site. Subjects 
who did not meet all eligibility requirements but whose tumor tissue was tested for 
FGFR1 amplification by the central laboratory will be entered to the Assay Validation 
Population.
6.2.
Subject Completion Criteria
A completed subject is one who has discontinued study treatment for reasons listed in 
Section 6.3 and completed the follow-up visit 30 days after last dose, or has died while on 
study.
6.3.
Permanent Discontinuation from Study Treatment
Subjects will receive study treatment until disease progression, death or unacceptable 
toxicity, including meeting stopping criteria for liver chemistry defined in Section 4.6.1. 
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 (which may include safety, behavioral or administrative 
reasons)


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
a dose delay of >14 days unless the investigator or GSK Medical Monitor agree 
that further treatment may benefit the subject

intercurrent illness that prevents further administration of study treatment(s)

termination of the study by Sponsor

Subject is lost to follow-up.
The primary reason study treatment was permanently discontinued must be documented 
in the subject’s medical records and eCRF. 
Subjects who permanently discontinue chemotherapy may continue GSK3052230 until 
meeting one of the reasons for discontinuation stated above.  The primary reason each 
study treatment was discontinued must be documented in the medical record and on the 
eCRF. The reason for discontinuing GSK3052230 may differ from the reason 
chemotherapy was discontinued. 
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 Table (see Section 7.1).
6.4.
Study Completion
The study will be considered completed when at least 80% of subjects have completed 
the study.  Upon completion of the study, if subjects are still continuing to receive benefit 
from GSK3052230, plans will be developed to provide continued access to GSK3052230 
for those subjects.
Per the EU Clinical Trial Directive, the end of the study is defined as the last subject’s 
last visit.
6.5.
Treatment after the End of the 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.
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.


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The timing of each assessment is listed in the Time and Events Table (Section 7.1).  The 
timing and number of the planned samples may be altered to a minor extent (no more 
than 1 to 3 additional samples) during the course of the study based on newly available 
data (e.g. to obtain samples closer to the time of peak plasma concentrations).  The 
change in timing or addition of time points for any of the planned samples must be 
approved and documented by GSK, but this will not constitute a protocol amendment. 
The institutional review board (IRB) or ethics committee will be informed of any safety 
issues that require alteration of the safety monitoring scheme. Specific blood volumes for 
analysis will be specified in the SPM. 
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 Table
This section consists of the Time and Events Table to describe assessment windows and 
sequencing of study-specific assessments and procedures. 


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Table 10
Time and Events Schedule
Time and Events Schedule for FGF117360
Screen
Cycle 1
Cycle 2
Additional Cycles
Every 4 
Cycles, 
D1
EOT
30 day 
F/U
D1
D8
D15
D1
D8
D15
D1
D8
D15
Visit Window
Once the subject provides consent, a tumor sample may be submitted for Arms A and B for FGFR1 amplification at any time (there is no time limit or window).  
All other screening assessments should be conducted within 30 days of C1D1. Visit windows of ±2 days during study through EOT, +7 days for F/U. For Arm A 
subjects who wish to start chemotherapy prior to GSK3052230 screening period is 30 days +3 to allow baseline imaging scans to be performed prior to 
chemotherapy but within 30 +3 days of GSK3052230 first dose.
Informed consent
Main study and PGx optional consent; register 
subject
X
Medical History, 
Medical history, review of inclusion & exclusion 
criteria 
X
Physical examand height 
(baseline only)
Not needed C1D1 if screening assessments 
within prior 72 hrs. Complete physical exam at 
screening. Abbreviated disease-oriented 
physical exam subsequently.
X
X
X
X
X
X
Weight
Note, during dosing period weight should be 
captured on Day 1 of each cycle.  It can be 
obtained more frequently per institutional 
standards (example: if required at each infusion)
X
X
X
X
X
X
Ophthalmologic Exam
To be performed by ophthalmologist or qualified 
optometrist. (Visit windows of ±7 days post 
baseline).
X
Perform assessment if subject discontinues prior to C4.
C4 only
ECHO
Perform at EOT if subject discontinues prior to 
C4. Visit windows of ±7 days post baseline.
X
C4 only
early 
disc
ECOG PS
Obtain prior to infusion
X
X
X
X
Vital Signs
Within 20 min before start of first chemotherapy 
infusion and within 20 min before start of 
GSK3052230 infusion.
X
X
X
X
Forced Vital Capacity
Assess D1 of every odd cycle, Arm C only, Visit 
windows of ±7 days post baseline.
X
X
Odd
X
Hematology and Chemistry
Not needed C1D1 if screening assessments 
within prior 72 hrs. See Table 12 for analytes. In 
X
X
X
X
X
X
X
A 
only
X


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Time and Events Schedule for FGF117360
Screen
Cycle 1
Cycle 2
Additional Cycles
Every 4 
Cycles, 
D1
EOT
30 day 
F/U
D1
D8
D15
D1
D8
D15
D1
D8
D15
addition Arm A: D8 of additional cycles while 
receiving paclitaxel + carboplatin only
Coagulation and 
pancreatic markers
See Table 12 for analytes
X
X
X
Thyroid
TSH at Screening.
X
TSH every 2 cycles for the first year and then every 4 cycles. If TSH is 
positive, then test total T3, total T4, and free T4.
Pregnancy
serum test +7 days of first dose; urine or serum 
test onward
X
X
Urinalysis
Obtain prior to infusion of GSK3052230 on 
C1D1
X
X
X
X
ECG (single read)
Prior to GSK3052230 infusion and 1 hr (±10 
min) after end of GSK3052230 i.v. on C1D1. 
Prior to GSK3052230 i.v. onward
X
X
X
X
As clinically 
indicated
X
X
Pharmacokinetics 
See Table 11
X
X
X
X
X
X
Immunogenicity 
Obtain prior to infusion of GSK3052230
X
X
D1 of every 2 cycle, C4 to C15 
X
Archival Tumor Tissue 
Archived tumor tissue (or fresh biopsy if no 
archival tissue). Once the subject provides 
consent, a tumor sample may be submitted for 
Arms A and B for FGFR1 amplification at any 
time (there is no time limit or window). 
X
Circulating cell-free DNA 
Sample 
Predose. First sample +7 days prior to C1D1
X
X
Circulating Biomarkers 
Plasma sample collected predose (+7 days prior 
to C1D1)
X
X
Arm C: D1 every cycle 
(1week) for 1 year, then D1 
every 2 cycles (2weeks)
X
Blood sample for PGx
Collect any time on study but only if PGx 
informed consent has been signed; preferred on 
C1D1 after dosing.
X
Brain Scan 
Obtain only if symptomatic
X
every 12 weeks 1 week if positive at Screening, or as clinically indicated
Bone Scan
X
As clinically indicated


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Time and Events Schedule for FGF117360
Screen
Cycle 1
Cycle 2
Additional Cycles
Every 4 
Cycles, 
D1
EOT
30 day 
F/U
D1
D8
D15
D1
D8
D15
D1
D8
D15
Radiologic and Disease 
Assessment
CT scan, PET-CT scan or MRI. Imaging 
modality consistent during study and not change 
X
Every 2 cycles (1 week) for 1 
year; thereafter every 4 cycles 
(2 week)
X
LCSS (Arms A and B); 
LCSS-meso (Arm C) 
Must be administered first before any other tests 
or procedures. Study staff should check for 
completeness.
X
X
X
X
X
X
GSK3052230
30 minute infusion. 
X
X
X
X
X
X
X
X
X
ARM A: Paclitaxel + 
Carboplatin 
GSK3052230 infused & observed 1 hr prior to 
chemotherapy doses. May start chemotherapy 
during screening period, see inclusion #2
X
X
X
ARM B: Docetaxel 
GSK3052230 infused & observed 1 hr prior to 
chemotherapy infusions.
X
X
X
ARM C: Pemetrexed +
Cisplatin 
GSK3052230 infused & observed 1 hr prior to 
chemotherapy infusions.
X
X
X
Adverse Event 
Assessment
X
Continuous monitoring during study
Concomitant Medications 
X
Continuous monitoring during study


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Table 11
Pharmacokinetic Sampling Schedule
FGF117360 Pharmacokinetic Sampling Schedule
Limited PK
Extensive PK
Extensive PK
Extensive PK
Time 
When
Window
Arm A
Arm B
Arm C
n=20pts in each arm 
n>=10pts
n>=10pts
n>=10pts
Cycle 1 Day 1
Prior to infusion of 
GSK3052230
Up to 12 hr prior to infusion of 
GSK3052230
GSK3052230 PK
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 PK
End of infusion of 
GSK3052230
Up to 5 min prior to end of 
infusion of GSK3052230
GSK3052230 PK
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 PK
1hr after end of infusion of 
GSK3052230
10 min but after ECG
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 PK
2hr after end of infusion of 
GSK3052230 or end of 
docetaxel infusion
10 min or up to 5 min prior to 
end of docetaxel infusion
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 PK
Cycle 1 Day 8
Prior to infusion of 
GSK3052230
Up to 12 hr prior to infusion of 
GSK3052230
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 PK
Cycle 2 Day 1
Prior to infusion of 
GSK3052230
Up to 12 hr prior to infusion of 
GSK3052230
GSK3052230 PK
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 PK
End of infusion of 
GSK3052230
Up to 5 min prior to end of 
infusion of GSK3052230
GSK3052230 PK
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 PK
1 hr after start of paclitaxel 
infusion or end of 
docetaxel or pemetrexed 
infusion
10 min for paclitaxel or up to 
5 min prior to end of docetaxel 
infusion or up to 1 min prior to 
end of pemetrexed infusion
GSK3052230 
PK
Paclitaxel PK
GSK3052230 
PK
Docetaxel PK
GSK3052230 PK
Pemetrexed PK
Cisplatin PK
1 hr after end of 
pemetrexed infusion
20 min
Pemetrexed PK
Cisplatin PK
End of paclitaxel infusion 
or 2 hr after end of 
docetaxel or pemetrexed 
infusion
up to 5 min prior to end of 
paclitaxel infusion or 20 min 
for docetaxel and pemetrexed 
Paclitaxel PK
Docetaxel PK
Pemetrexed PK
Cisplatin PK
2 hr after end of paclitaxel 
infusion or 5 hr after end 
of docetaxel or 
pemetrexed infusion
30 min
(selected sites)
GSK3052230 
PK
Paclitaxel PK
(selected sites)
GSK3052230 
PK
Docetaxel PK
(selected sites)
GSK3052230 PK
Pemetrexed PK
Cisplatin PK


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FGF117360 Pharmacokinetic Sampling Schedule
Limited PK
Extensive PK
Extensive PK
Extensive PK
Time 
When
Window
Arm A
Arm B
Arm C
Cycle 4 Day 1
Cycle 6 Day 1
Cycle 12 Day 1
Prior to infusion of 
GSK3052230
Up to 12 hr prior to infusion of 
GSK3052230
GSK3052230 PK
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 PK
Cycle 4 Day 1
End of infusion of 
GSK3052230
Up to 5 min prior to end of 
infusion of GSK3052230
GSK3052230 PK
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 PK
Cycle 6 Day 1
Cycle 12 Day 1
EOT
GSK3052230 PK
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 PK
30 days FU
At time of immunogenicity 
sample
GSK3052230 PK
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 PK
All subjects will have PK sampling performed (either Limited PK or Extensive PK). Serial PK samples will be performed on at least the first 10 subjects in Arm A and B with at least 6 
subjects having serial PK at the MTD/MFD. For Arm C, at least 6 subjects will have serial PK sampling. After an adequate PK profile data has been achieved, the remaining subjects 
will participate in the population PK sampling. Depending on emerging data, the timing of PK samples may change and PK samples may not be required from every subject in the 
study.


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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 3.2.
Baseline (Screening) assessments obtained will include:

Complete physical examination, including height (in cm) and weight (in kg).

Vital signs (i.e., blood pressure, temperature, respiratory rate, pulse rate)

Eastern Cooperative Oncology Group (ECOG) performance status

Clinical laboratory tests: hematology, clinical chemistry [and urinalysis]

Serum beta-human chorionic gonadotropin (-HCG) pregnancy test for female 
subjects of childbearing potential only

12-lead electrocardiogram (ECG)

Echocardiogram (ECHO) 

LCSS for Arms A & B

For Arm C only: LCSS (meso) and forced vital capacity

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
Ophthalmologic examination, ocular, and cardiovascular medical history/risk factors will 
be assessed at baseline.
Assessment regarding deregulation of FGF signaling pathway (e.g. FGFR gene 
amplification, FGF ligand overexpression, etc) is required during screening.  Archival 
tissue may be used for this analysis. If archival tissue is not available, a fresh biopsy will 
be required. This will be assessed by a central laboratory for Arms A and B.
For Arm C, forced vital capacity will be assessed at screening.
7.3.
Safety Evaluations
Planned time points for all safety assessments are provided in the Time and Events Table 
(Section 7.1).


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7.3.1.
Physical Examinations
A complete physical examination will include assessments of the head, eyes, ears, nose, 
throat, skin, thyroid, neurological, lungs, cardiovascular, abdomen (liver and spleen), 
lymph nodes and extremities. Height and weight will also be measured and recorded.
A brief physical examination will include assessments of the lungs, cardiovascular 
system, and abdomen (liver and spleen).
7.3.2.
ECOG Performance Status
The performance status will be assessed using the ECOG scale (see Appendix 4) as 
specified in the Time and Events Table (Section 7.1).
7.3.3.
Vital Signs
Vital sign measurements will include systolic and diastolic blood pressure, temperature, 
respiration rate and pulse rate.  All vital sign measurements will be obtained after the 
subject has rested for at least 5 minutes in a semi-supine position.  Vital signs will be 
measured more frequently if warranted by clinical condition of the subject.  On days 
where vital signs are measured multiple times, temperature does not need to be repeated 
unless clinically indicated. Whenever blood pressure and heart rate are measured at the 
same nominal time as a blood draw, the blood pressure and heart rate will be prior to the 
blood draw. Refer to the SPM for details regarding measurement of vital signs.
7.3.4.
Forced Vital Capacity
Forced vital capacity will be measured in Arm C at each scheduled disease assessment 
using standard methods (Refer to the SPM for details)
7.3.5.
Electrocardiogram
Single 12-lead ECGs will be obtained at designated time points during the study using an 
ECG 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 and is in a 
semi-recumbent position. 
The QT interval should be corrected for heart rate by Fridericia’s formula (QTcF). 
Additional QTc readings may be necessary.
Refer to the SPM for details regarding ECG procedures.
7.3.6.
Echocardiogram
ECHOs will be performed at baseline to assess cardiac ejection fraction and cardiac valve 
morphology for the purpose of study eligibility and Cycle 4, as specified in the Time and 
Events Table (Section 7.1).  Additional ECHO assessments may be performed if 
clinically warranted. The evaluation of the echocardiographer should include an 


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evaluation for left ventricular ejection fraction (LVEF) and both right and left-sided 
valvular lesions.
Copies of all ECHOs performed on subjects who experience an absolute decrease >10% 
in LVEF compared to baseline concurrent with LVEF <lower limit of normal (LLN), or 
who experience valvular toxicity, may be required by GSK for review.
7.3.7.
Ophthalmologic Examinations
An ophthalmologic exam will be performed at baseline and at Cycle 4 (or as clinically 
appropriate), as specified in the Time and Events Table (Section 7.1).  These exams will 
be performed by an ophthalmologist or qualified optometrist and includes a slit-lamp 
examination and intraocular pressure.  During the study, ophthalmologic assessments 
performed by the investigator will include inspection of the external eye to assess for
redness and query of subjects for symptoms of photophobia, vision problems, or eye pain.  
If at any time the subject complains of photophobia, changes in vision, or eye pain; the 
ophthalmic examination finding are abnormal; or visual acuity has worsened by 3 lines or 
more since the start of the study, the subject will be referred for a formal evaluation, 
including a slit-lamp examination and intraocular pressure, by a qualified 
ophthalmologist.
7.3.8.
Laboratory Assessments
All protocol required laboratory assessments, as defined in (Table 12) should be 
performed according to the Time and Events Table (Section 7.1).  Details for the 
preparation and shipment of samples to the central laboratory 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 subject 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.
Hematology, clinical chemistry, urinalysis and additional parameters to be tested are 
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Table 12
List of Clinical Laboratory Tests
Hematology
Platelet Count
Automated WBC Differential:
Red blood cell (RBC) Count
Neutrophils (absolute)
White blood cell (WBC) Count 
(absolute) 
Lymphocytes (absolute)
Hemoglobin
Monocytes (absolute)
Eosinophils (absolute)
Basophils (absolute)
Clinical Chemistry
Potassium, Sodium, Chloride, Total carbon dioxide, total Calcium, ionized calcium*, magnesium, phosphate, 
albumin, glucose (fasting),
Blood urea nitrogen (BUN), Creatinine, Uric Acid, creatinine clearance
Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Gamma glutamyl transferase (GGT), 
Alkaline phosphatase, Total bilirubin (if elevated also test direct bilirubin) 
Thyroid hormone: TSH at Screening; every 2 cycles for the first year and then every 4 cycles. If TSH is 
positive, also test total T3, total T4, and free T4.
Pancreatic tests (amylase and lipase)
Coagulation tests (prothrombin time, partial thromboplastin time, international normalized ratio, and 
fibrinogen)
Routine Urinalysis
pH, glucose, protein, blood and ketones by dipstick
Microscopic examination (if blood or protein is abnormal)
Other screening tests
Pregnancy test for females (serum at screening, urine or serum post dose)
*Ionized calcium collected may not be collected in some selected sites and only total calcium is collected for 
subjects regarding safety monitoring.
7.3.9.
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 7 days prior to the first dose of study treatments. 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 in 
Section 10.1 during the study until 6 months following the last dose of chemotherapy or 4 
weeks after the last dose of GSK3052230, whichever is latest.
Any pregnancy that occurs during study participation (note, study participation is defined 
as the time of the first dose of study drug GSK3052230 is administered) 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 AE or SAE. Spontaneous abortions must be reported as an SAE.


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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(s), must be promptly reported to GSK.
7.4.
Evaluation of Anti-Cancer Activity
Disease assessment will include imaging (e.g., computed tomography [CT] scan, 
magnetic resonance imaging [MRI]) as appropriate for the specific tumor type.  Disease 
assessment will be completed within 30 days prior to the first dose of GSK3052230, then 
every other treatment cycle for the first year. Subsequent assessments will follow the 
Time and Events Table (Section 7.1), which also should be consulted 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 7 days is permitted to allow for flexible scheduling. If the last 
radiographic assessment was more than 2 cycles or a maximum of 8 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.
Disease progression and response evaluations will be determined according to the 
definitions established in RECIST 1.1 [Eisenhauer, 2009].  Subjects whose disease 
responds (either complete response [CR] or partial response [PR]) should have a 
confirmatory disease assessment performed no earlier than 4 weeks after the date of 
assessment during which the response was demonstrated. More frequent disease 
assessments may be performed at the discretion of the investigator. Please see Section 
7.4.1.5 for the evaluation of best overall response. To ensure comparability between the 
baseline and subsequent assessments, the same method of assessment and the same 
technique will be used when assessing response. 
Disease response will also be quantified by change in volume to support the exploratory 
objectives.   Comparison between RECIST evaluations, linear tumor dimensions, and 
variations in tumor volume will be performed [O’Connor, 2008].
Inclusion of up to three pre-study tumor imaging scans performed prior to baseline scans 
at study entry will also be encouraged in subjects whose scans are available for review.  
Prior tumor imaging scans will be analyzed (see SPM for additional details) and 
quantitative tumor data (e.g., tumor measurements, tumor volumes) will be generated.  
Depending on data availability, the slope of tumor growth prior to study entry and 
following treatment may be calculated and compared in an exploratory analysis.  Such 
comparisons may be important in evaluation of the clinical significance of subjects 
achieving a clinical response, particularly in those subjects achieving SD.
Research sites will be trained in volumetric analysis using a standardized review 
platform.  Depending on the outcome of site based assessments, images may be collected 
centrally for further analysis.
Please see the SPM for specific guidelines for CT and MRI acquisitions and analysis.
CT: For contrast enhanced CT, contiguous slices (no gap) may be no greater than 5mm. 
However, 3mm slice thickness or less is strongly preferred for volume analysis. MRI is 


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acceptable, but when used, scanning should be optimized for the evaluation of the type 
and site of disease and must be measured in a consistent anatomic plane for each 
timepoint. Whenever possible, the same scanner should be used [Eisenhauer, 2009].
For Arms A and B, RECIST 1.1 analysis, the minimum size of a measurable baseline 
lesion should be twice the slice thickness, with a minimum lesion size of 10 mm when 
the slice thickness is 5 mm. The Image Acquisition Guidelines portion of the SPM should 
be consulted for additional details on imaging protocols.
For Arm C, modified RECIST will be used. Tumor thickness perpendicular to the chest 
wall or mediastinum will be measured in two positions at three separate levels on thoracic 
CT scans. The sum of the six measurements defines a pleural unidimensional measure. 
Bidimensionally measureable lesions will be measured unidimensionally as for RECIST 
1.1. All measurements were added to obtain the total tumor measurement. The Image 
Acquisition Guidelines portion of the SPM should be consulted for additional details on 
imaging protocols.
Brain Scan: In subjects with known brain metastases (criteria outlined in Section 3.2), a 
contrast-enhanced MRI (preferred) or CT of the brain must be obtained within 30 days 
prior to receiving the first dose of the study medication.  Assessment of brain metastases 
must be repeated as part of the regular assessment of target and non target lesions, and 
the same imaging method should be used.
In subjects with no history of brain metastases at baseline and no clinical signs or 
symptoms indicative of the presence of brain metastases, no baseline MRI or CT of the 
brain is necessary, nor is any routine brain imaging necessary. MRI or CT of the brain 
will be required in case of new clinical signs and symptoms indicative of brain 
metastases.
Bone Scan: Including evaluation of skull, total spine, clavicle, ribs, pelvis and long 
bones. Other imaging modalities are allowed such as PET or MRI.
If a subject’s bone-scan lesions are consistent with tumor metastases, or are consistent 
with non-malignant lesions, confirmatory imaging assessments are not necessary.  The 
anatomic sites and nature of the lesions must be documented in the eCRF.
If bone scan lesions are equivocal for tumor metastases, a confirmatory imaging 
assessment must be performed using X-ray, CT, or MRI to determine the nature of the 
lesions. The lesion sites and nature of lesions must be documented in the eCRF.  For 
lesions that are confirmed as tumor metastases, the same imaging modality must be used 
for all subsequent follow-up bone lesion assessments.
Volumetric Analysis: Retrospective evaluation of tumor volumes will also be performed 
in subjects with sufficient CT or MRI imaging data. Comparison between RECIST 
evaluations, linear tumor dimensions, and variations in tumor volume will be performed 
[O’Connor, 2008].


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7.4.1.
Evaluation of Response in Arm A and Arm B (RECIST 1.1)
7.4.1.1.
Evaluation of target lesions
Definitions for assessment of response for target lesion(s) are as follows:

Complete Response (CR): Disappearance of all target lesions. Any pathological 
lymph nodes must be <10 mm in the short axis.

Partial Response (PR): At least a 30% decrease in the sum of the diameters of 
target lesions, taking as a reference, the baseline sum of the diameters (e.g. percent 
change from baseline).

Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient 
increase to qualify for progressive disease.

Progressive Disease (PD): At least a 20% increase in the sum of the diameters of 
target lesions, taking as a reference, the smallest sum of diameters recorded since the 
treatment started (e.g. percent change from nadir, where nadir is defined as the 
smallest sum of diameters recorded since treatment start).  In addition, the sum must 
have an absolute increase from nadir of 5mm.

Not Applicable (NA): No target lesions at baseline.

Not Evaluable (NE): Cannot be classified by one of the five preceding definitions.
NOTE:

If lymph nodes are documented as target lesions the short axis is added into the sum 
of the diameters (e.g. sum of diameters is the sum of the longest diameters for non-
nodal lesions and the short axis for nodal lesions).  When lymph nodes decrease to 
non-pathological size (short axis <10mm) they should still have a measurement 
reported in order not to overstate progression.

If at a given assessment time point all target lesions identified at baseline are not 
assessed, sum of the diameters cannot be calculated for purposes of assessing CR, 
PR, or SD, or for use as the nadir for future assessments.  However, the sum of the 
diameters of the assessed lesions and the percent change from nadir should be 
calculated to ensure that progression has not been documented.  If an assessment of 
PD cannot be made, the response assessment should be NE.

All lesions (nodal and non-nodal) should have their measurements recorded even 
when very small (e.g., 2 mm).  If lesions are present but too small to measure, 5 mm 
should be recorded and should contribute to the sum of the diameters, unless it is 
likely that the lesion has disappeared in which case 0 mm should be reported.

If a lesion disappears and reappears at a subsequent time point it should continue to 
be measured.  The response at the time when the lesion reappears will depend upon 
the status of the other lesions.  For example, if the disease had reached a CR status 
then PD would be documented at the time of reappearance.  However, if the response 
status was PR or SD, the diameter of the reappearing lesion should be added to the 
remaining diameters and response determined based on percent change from baseline 
and percent change from nadir.


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7.4.1.2.
Evaluation of non-target lesions
Definitions for assessment of response for non-target lesions are as follows:

Complete Response (CR): The disappearance of all non-target lesions. All lymph 
nodes identified as a site of disease at baseline must be non-pathological (e.g. <10 
mm short axis).

Non-CR/Non-PD: The persistence of 1 or more non-target lesion(s) or lymph nodes 
identified as a site of disease at baseline ≥10 mm short axis.

Progressive Disease (PD): Unequivocal progression of existing non-target lesions. 

Not Applicable (NA): No non-target lesions at baseline.

Not Evaluable (NE): Cannot be classified by one of the four preceding definitions.
NOTE:

In the presence of measurable disease, progression on the basis of solely non-target 
disease requires substantial worsening such that even in the presence of SD or PR in 
target disease, the overall tumor burden has increased sufficiently to merit 
discontinuation of therapy.

Sites of non-target lesions, which are not assessed at a particular time point based on 
the assessment schedule, should be excluded from the response determination (e.g. 
non-target response does not have to be "Not Evaluable"). 
7.4.1.3.
New lesions
New malignancies denoting disease progression must be unequivocal. Lesions identified 
in follow-up in an anatomical location not scanned at baseline are considered new 
lesions.
Any equivocal new lesions should continue to be followed.  Treatment can continue at 
the discretion of the investigator until the next scheduled assessment. If at the next 
assessment the new lesion is considered to be unequivocal, progression should be 
documented.
7.4.1.4.
Evaluation of overall response
Table 13 presents the overall response at an individual time point for all possible 
combinations of tumor responses in target and non-target lesions with or without the 
appearance of new lesions for subjects with measurable disease at baseline.


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Table 13
Evaluation of Overall Response for Subjects with Measurable 
Disease at Baseline
Target Lesions
Non-Target Lesions
New Lesions
Overall Response
CR
CR or NA
No
CR
CR
Non-CR/Non-PD or NE
No
PR
PR
Non-PD or NA or NE
No
PR
SD
Non-PD or NA or NE
No
SD
NE
Non-PD or NA or NE
No
NE
PD
Any
Yes or No
PD
Any
PD
Yes or No
PD
Any
Any
Yes
PD
CR=complete response, PR = partial response, SD=stable disease, PD=progressive disease, NA= Not applicable, and 
NE=Not Evaluable
NOTE:

Subjects with a global deterioration of health status requiring discontinuation of 
treatment without objective evidence of disease progression at that time should be 
classified as having "symptomatic deterioration."  Objective response status is 
determined by evaluations of disease burden.  Every effort should be made to 
document the objective progression even after discontinuation of treatment. 

In some circumstances, it may be difficult to distinguish residual disease from 
normal tissue.  When the evaluation of CR depends on this determination, it is 
recommended that the residual lesion be investigated (fine needle aspirate/biopsy) to 
confirm the CR.
Confirmation Criteria:
To be assigned a status of PR or CR, a confirmatory disease assessment should be 
performed no less than four weeks (28 days) after the criteria for response are first met.
7.4.1.5.
Evaluation of best overall response
The best overall response is the best response recorded from the start of the treatment 
until disease progression/recurrence and will be determined programmatically by GSK 
based on the response assessment at each time point. 

To be assigned a status of SD, the post-baseline disease assessment must have met 
the SD criteria no less than 10 weeks (per Time and Events schedule Section 7.1). 

If the minimum time for SD is not met, best response will depend on the subsequent 
assessments.  For example if an assessment of PD follows the assessment of SD and 
SD does not meet the minimum time requirement the best response will be PD. 
Alternative subjects lost to follow-up after an SD assessment not meeting the 
minimum time criteria will be considered not evaluable.


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Tips on Lymph Node Measurements:
Lymph nodes are considered as a separate organ to measure, and up to two lymph nodes 
can be measured per patient by RECIST v1.1. For unidimensional lymph node 
measurements, use the short axis of the lymph node at baseline and then at every 
followup scan. To be considered as pathologically enlarged and measurable at baseline, 
the lymph node short axis diameter should be ≥15 mm.
7.4.2.
Evaluation of Response in Arm C: Mesothelioma
7.4.2.1.
Mesothelioma Tumor Imaging
Clinical trials of therapeutic agents in MPM may be compromised by inaccuracy of 
tumor measurements due to the unique pattern of growth of mesothelioma [Byrne, 2004; 
Tsao, 2011]. Malignant mesothelioma commonly grows as a rind and thus may not 
produce spherical lesions with bidimensional, measurable diameters [Byrne, 2004]. 
Modification of RECIST criteria have been recommended to address the difficulties in 
measurement of lesions [Byrne, 2004; Tsao, 2011]. In subjects with mesothelioma, it is 
requested that disease assessments using both RECIST v1.1 criteria AND modified 
RECIST criteria be performed.
Uni-dimensional measurements of tumor thickness perpendicular to the chest wall or 
mediastinum should be performed, measured in 2 sites at 3 different levels on the CT 
scan. Transverse cuts used for measurement must be at least 1 cm apart, and related to 
anatomical landmarks in the thorax, preferably above the level of division of the main 
bronchi. At reassessment, pleural thickness must be measured at the same position and 
level. Nodal, subcutaneous, and other bidimensionally measurable lesions are measured 
unidimensionally as per the RECIST v1.1 criteria. Unidimensional measurements are 
added to produce the total tumor measurements (e.g., the sum of 6 pleural thickness 
measurements = one univariate diameter).
Overall tips for measurement of mesothelioma by modified RECIST [Tsao, 2011]:
1.
Larger lesions are easier and more accurate to measure. Choose the larger or thickest 
of the pleural disease to measure. Magnifying the image may make an easier 
measurement.
2.
The short-axis diameter is defined as the shortest pathway from the tip of the tumor 
to the chest wall.
3.
Ensure that that differentiation of normal chest wall from tumor is easy at the point 
of measurement
4.
To ensure accuracy, all measurements must be performed electronically in the same 
window setting on consecutive studies. It is recommended that the “soft tissue” 
setting (not lung windows) be used, as it enables accurate pleural mass 
measurements with the electronic calipers and avoids the incorporation of chest wall 
or mediastinal fat within the calculations.


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5.
CT scan slices up to 5 mm can be used, but for greater accuracy, thinner slices such 
as 2.5 mm are preferable. Ideally, all subsequent CT scans should use the same slice 
thickness.
6.
To limit interobserver variability, in measuring tumor response, it is preferred that 
the same clinician measure the tumors at baseline and on all subsequent CT scans.
7.
The pleural disease to be measured should have a short-axis diameter of at least 1 
cm, as lesions less than 1 cm are considered nonmeasurable.
8.
To obtain the short axis of the disease, with electronic calipers, measure the distance 
between the point where the tumor abuts the chest or the mediastinal border and the 
point where the pleural disease touches the lung. The shortest route possible is the 
one perpendicular to the chest wall/mediastinum.
9.
Avoid measuring regions where the tumor infiltration obscures the interface of tumor 
to normal tissue. A good interface for measurement usually is one where the tumor 
abuts fat or an intact rib/vertebral body, as the density of the pleural tumor differs 
significantly from bone or fat and the difference can be easily observed. Avoid 
choosing an interface of tumor with muscle, as muscle and tumor have similar CT 
densities and are often difficult to distinguish when they abut one another.
10. Following the instructions in #5, choose three different axial slices, preferably above 
the level of the main bronchi and record two measurements per slice, thus resulting 
in six separate measurements.
11. If any nodal, subcutaneous or other bidimensionally measurable lesions are 
available, they should undergo unidimensional measurements by RECIST v1.1 and 
be added to the total obtained in #7 above.
7.4.2.2.
Prior Scan collection
Collection of up to three prior tumor imaging scans performed prior to baseline scans at 
study entry will also be encouraged in subjects whose scans are available for review. 
These scans may be collected and sent to an independent radiologist for review. The 
slope of tumor growth prior to study entry and following treatment may be compared in 
subsequent analyses. Such comparisons may be important in evaluation of the clinical 
significance of subjects achieving a clinical response, particularly in those subjects 
achieving SD.
7.4.3.
Patient Reported Outcomes
The Lung Cancer Symptom Scale (LCSS) or the Lung Cancer Symptom Scale-
mesothelioma (LCSS-meso) will be self-administered by subjects (patient scales) and 
completed by the investigator (observer scales) as indicated in the Time and Events 
schedule (Table 10). The LCSS consists of 9 patient-reported items and 6 observer 
reported items, the LCSS-meso consists of 8 patient-reported items, and are validated in 
lung cancer and in mesothelioma patients [Hollen, 2006]. Using visual analogue scales 
(range from 0 to100), the patient scale measures the intensity of patient responses for 
appetite, fatigue, cough, dyspnea, hemoptysis, pain, and summary items symptoms of 
lung cancer, activity level and quality of life. An example questionnaire can be found in 
the SPM. The LCSS and LCSS-meso was chosen because of its focus on disease-related 


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symptoms, the possibility to combine the patient’s perception with the investigator’s 
contextual knowledge, its demonstrated concept and content validity, ease of application 
and minimal burden to patients. 
It is important that the LCSS and LCSS-meso patient scale is administered at the start of 
the clinic visit before any other study assessments are performed.
7.5.
Pharmacokinetics
7.5.1.
Blood Sample Collection for Pharmacokinetics
Blood samples of approximately 4 mL for PK analysis of GSK3052230 will be collected 
at the time points indicated in the Time and Events Schedule (Section 7.1). For subjects 
in Arm A, a 4mL blood sample for PK analysis of paclitaxel may be collected and 
subjects in Arm B, a 4mL blood sample for PK analysis of docetaxel may be collected 
(see 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.
The timing and frequency of the PK sampling may be adjusted based on emerging data. 
Details on PK blood sample collection, processing, storage and shipping procedures are 
provided in the SPM.
7.5.2.
Pharmacokinetic Sample Analysis
Plasma analysis will be performed under the management of Worldwide Bioanalysis, 
Drug Metabolism and Pharmacokinetics, GSK. Concentrations of GSK3052230 and 
selected chemotherapy will be determined in plasma samples using the currently 
approved analytical methodologies.  Raw data will be stored in the Good Laboratory 
Practice Archives, GSK.
7.6.
Immunogenicity
Plasma samples for determination of anti- GSK3052230 antibodies will be taken from all 
subjects in this study as a safety measurement for GSK3052230 at the time-points 
specified in the Time and Events Table in Section 7.1.  Timing of the assessments may be 
adjusted based on emerging data.
Samples will be analyzed for the presence of anti- GSK3052230 antibodies by immuno-
electrochemiluminescent (ECL) screening assays.  If samples contain anti- GSK3052230 
antibodies as determined by the ECL screening assay, they will be further characterized 
for specificity and antibody titers.  The immunogenicity assessment report will include 
the incidence and levels of anti- GSK3052230 binding antibodies.
Samples obtained for immunogenicity will be retained in long term storage and may be 
characterized for neutralizing activity if a positive response is observed.


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7.7.
Translational Research
7.7.1.
Central Confirmation of FGF Signalling Pathway Status and 
Translational Research
Collection of archival tumor tissue is required for all subjects (see Time and Events 
Table; Section 7.1); if not available a fresh sample will be required. A formalin fixed 
paraffin embedded tumor block is requested or if not available, approximately 15 sections 
will be needed. Details of the tumor biopsy collection including amount, processing, 
storage, and shipping procedures are provided in the SPM.
In Arms A and B, a requirement for inclusion is evidence of FGFR1 gene amplification 
in tumor tissue as determined by a central laboratory (CLIA or appropriate certification) 
using a laboratory developed test.
In Arm C, FGF2 and/or FGFR1  expression will be evaluated retrospectively by IHC to 
determine if expression levels of these proteins are associated with response to 
GSK3052230
Any remaining tissue from this study may be used for:

Development and validation of a potential IUO assay and companion diagnostic test, 
e.g., but not limited to FGFR1 gene amplification by FISH or FGF2 and/or FGFR1 
expression by IHC.

Alternative biomarkers of FGF pathway signalling such as other ligands or receptors. 

Biomarker research (protein, RNA and DNA) including status of RTK/PI3K/AKT 
pathways and cancer development and additional testing of DNA, RNA, or protein 
biomarkers related to the function of GSK3052230 if ongoing research identifies or 
defines additional predictive and prognostic biomarkers
It is essential that the required amount of tumor tissue is obtained in order to perform the 
FISH assay for entry into the study in Arms A and B, explore other potential measures of 
FGF signaling pathway deregulation in all arms including Arm C, and complete the 
necessary equivalency and precision testing requirements for the development of an IUO 
and potential companion diagnostic test.
Tissue samples/sections will be retained for the further confirmation using the IUO 
validated assay or potential companion diagnostic test, when available.  All samples will 
be retained for a maximum of 15 years after the last subject completes the trial.
7.7.2.
Peripheral Blood
7.7.2.1.
Plasma for Soluble Markers
Clusters of markers (e.g. cytokines and angiogenic factors [CAF]) circulating in the 
plasma have been found to correlate with tumor pathway activation. Soluble mesotheline-
related peptides (SMRP) have been shown to be clinical markers of MPM. Blood-based 
markers have the important advantage that specimens are readily available, simple to 
prepare and store, and can be taken prior to and during treatment. This allows for the 


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assessment of predictive markers based on the baseline evaluation as well as markers of 
activity and resistance based on changes that occur during treatment. Therefore, a broad 
panel of CAF, including FGF ligands, and SMRP will be evaluated in plasma and 
correlated with clinical outcome to treatment with GSK3052230.
Plasma will be collected at multiple times to evaluate circulating cytokines, angiogenesis 
and other soluble factors. Details of the blood collection (including volume to be 
collected), processing, storage and shipping procedures will be provided in the SPM.
7.7.2.2.
Circulating cell free DNA (cfDNA) Analysis
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 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 tumor 
burden.
Plasma samples collected at timepoints described in Time and Events Schedule (Section 
7.1) will be analyzed for mutations in genes relevant to RTK/MAPK/PI3K pathway and 
cancer biology in cfDNA.  Details of the blood collection (including volume to be 
collected), processing, storage and shipping procedures will be provided in the SPM.
7.8.
Pharmacogenetics
An important objective of the clinical study is pharmacogenetic (PGx) research. 
Participation in PGx is optional but all subjects who are eligible for the clinical study 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 research.
Subjects who provide consent will have a blood sample taken for analysis.  The 
presence/absence of genetic variations in selected candidate genes in DNA from blood 
will be analyzed to determine their relationship with response (safety, tolerability, 
pharmacokinetics (PK) and efficacy) to treatment with GSK2052230.
Information regarding PGx research is included in Appendix 1.  The institutional review 
board (IRB)/ethics committee (EC) and, where required, the applicable regulatory agency 
must approve the PGx assessments before these can be conducted at the site.  The 
approval(s) must be in writing and will clearly specify approval of the PGx assessments 
(i.e., approval of Appendix 1).  In some cases, approval of the PGx 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 assessments is being deferred and the study, except 
for PGx assessments, can be initiated.  When PGx assessments will not be approved, then 


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the approval for the rest of the study will clearly indicate this and therefore, PGx 
assessments will not be conducted.
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 AE or 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 AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of a 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/SAE). 
Events that do not meet the definition of an AE include:

Medical or surgical procedure (e.g., endoscopy, appendectomy); the condition that 
leads 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.


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8.2.
Definition of a SAE
A 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 
AEs. If a complication prolongs hospitalization or fulfills any other serious criteria, 
the event is serious.  When in doubt as to whether “hospitalization” occurred or was 
necessary, the AE should be considered serious.
Hospitalization for elective treatment of a pre-existing condition that did not worsen 
from baseline is not considered an AE.
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 as 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 subjects receiving anticoagulants).


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NOTE: Bilirubin fractionation is performed if testing is available.  If testing is 
not available, record presence of detectable urinary bilirubin on dipstick 
indicating direct bilirubin elevations and suggesting liver injury.  If testing is 
unavailable and a subject meets the criterion of total bilirubin ≥2 times ULN, 
then the event is still reported as a serious adverse event (SAE). If INR is 
obtained, include values on the SAE form. INR elevations >1.5 suggest severe 
liver injury. 

Any new primary cancers.

Cardiac toxicity including LVEF changes or treatment emergent cardiac valve 
toxicity.

Treatment emergent acute anterior uveitis.
8.3.
Disease-Related Events and/or Disease-Related Outcomes 
Not Qualifying as SAEs
An event that 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 SAE. Death due to disease under study is to be recorded on the Death 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.
8.4.
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., 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 AE or 
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 an 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.
8.5.
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 AE or SAE. 


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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?”
“Have you taken any new medicines, other than those provided in this study, since your 
last visit/contact?”
8.5.2.
Prompt Reporting of SAEs and Other Events to GSK
SAEs, pregnancies, and liver function abnormalities 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.


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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 
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.
Please refer to Section 4.6.1 for liver chemistry stopping criteria and follow-up 
procedures.
Methods for detecting, recording, evaluating, and following up on AEs and SAEs are 
provided in the 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.


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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.
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 eCRF. Additionally, 
a complete list of all prior anti-cancer therapies will be recorded in the eCRF.
If future changes are made to the list of permitted/prohibited medications, formal 
documentation will be provided by GSK and stored in the study file.  Any such changes 
will be communicated to the investigative sites in the form of a letter.
9.1.
Permitted Medication(s)
Subjects should receive full supportive care during the study, including transfusion of 
blood and blood products, and treatment with antibiotics, antiemetics, antidiarrheals, and 
analgesics, as appropriate. Pre-medication for chemotherapy is allowed per institutional 
guidelines.
The prophylactic use of hematopoietic colony stimulating factors is not recommended in 
Cycle 1 of the dose escalation portion of the study.  Local institutional practices vary 
globally, please discuss with the GSK medical team if there is a need to have 
prophylactic use for subjects during the dose escalation period or alternative dose finding 
period.  During expansion phase, growth factor support therapy (e.g., G-CSF, GM-CSF) 
may be administered as a prophylaxis for chemotherapy-related neutropenia according to 
the NCCN Clinical Practice Guidelines in Oncology: Myeloid Growth Factors v.1.2010 
[NCCN, 2010] or the European Organisation for Research and Treatment of Cancer 
guidelines for the use of G-CSFs [Aapro, 2011].  All growth factor use must be recorded 
as concomitant medication. 
Aromatase inhibitors, octreotide, and GnRH analogues are permitted if the subject has 
been receiving these therapies and continued therapy is deemed to be clinically indicated. 
Other non-investigational concomitant medications are discouraged unless medically 
indicated.
9.2.
Prohibited Medications
Investigational medications other than GSK3052230 are prohibited throughout the study. 
Anti-cancer agents other than those described within this protocol are prohibited.
Use of oral contraceptives (either combined or progesterone only)/estrogenic vaginal 
ring/percutaneous contraceptive patches/implants of levonorgestrel/injectable 
progesterone is prohibited in this study as it is not known if there is the potential of 
inhibition/induction of enzymes that affect the metabolism of estrogens and/or progestins.


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Agents known to alter the metabolism of the baseline chemotherapies, including 
non-traditional medications such as herbal remedies, should be avoided.  If such use is 
identified, then use should be properly recorded.
Pre-medication (such as anti-histamines or corticosteroids) prior to infusion of 
GSK3052230 should not be used unless the subject has experienced an infusion reaction 
to previous administration or it is a required component of concomitant chemotherapy.
9.3.
Permitted Non-Drug Therapies
Concurrent radiation therapy and surgery for solid tumors, including advanced or 
metastatic NSCLC, including resection of non-dominant metastases, is prohibited.
In exceptional cases, palliative radiation of bone metastasis may be allowed during the 
screening or treatment period if all of the following conditions are met:

There is no evidence of disease progression for subjects on study treatment

Intention of palliation is only for symptom control of bone pain and does not include 
any “target” lesion.

Single-dose palliation is planned (≤8 GY allowed; no prolonged or fractionated RT 
is allowed)

The investigator has reviewed the case with the GSK medical monitor.
GSK3052230 should be stopped 2 weeks prior to radiation and then restarted post-
radiation.
10.
LIFESTYLE AND/OR DIETARY RESTRICTIONS
10.1.
Contraception
10.1.1.
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. 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%.


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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. 
Contraceptive Methods with a Failure Rate of <1%

Intrauterine device or intrauterine system that meets the <1% failure rate as stated in 
the product label

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.
Complete abstinence from sexual intercourse or contraception must be practiced for 
14 days prior to first dose of study treatment, through the dosing period, and for at least 
4 weeks after the last dose of GSK3052230 or 6 months after the last dose of 
chemotherapy, whichever is latest.
10.1.2.
Male Subjects
For 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 until 6 months after the last dose of chemotherapy:

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 prior to first dose of chemotherapy 
treatment, through the dosing period, and for at least 6 months after the last dose of 
chemotherapy 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)


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11.
DATA MANAGEMENT
For this study, data will be collected using defined eCRFs, transmitted electronically to 
GSK and combined with data provided from other sources in a validated data system.
Patient reported data will be collected via paper questionnaires and will be entered into 
the eCRF centrally. Data will be checked for completeness by study staff immediately 
after completion by the subject and reasons for non-compliance will be noted.
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 
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.
12.
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS
12.1.
Considerations of statistical design
The sections below show the planned dose cohorts as well as the decision rules, by study 
arm, specifying the number of subjects with a confirmed objective response (according to 
RECIST 1.1 or modified RECIST for Arm C) needed for continuing enrolment or 
stopping for futility.  The methodology is based on the predictive probability of success if 
enrolment continues to 30 subjects [Lee, 2008].  The predictive probability design is 
similar to a Green-Dahlberg design in that it allows for early stopping for futility but the 
design allows evaluation of futility after every subject once a minimum enrolment has 
been reached whereas the Green-Dahlberg design does this at one fixed interim and at the 
end of enrolment. 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.  A 
randomized Phase II or Phase III study may be conducted based on the results from this 
study. 
12.2.
Hypotheses
No formal statistical hypotheses are being tested during the dose escalation portions of 
Arms A, B, and C.  Analysis of the data obtained from the dose escalation parts of the 
study will be focused on comparison between dose cohorts and only descriptive methods 
will be used in analysis of the data.
For the dose expansion portions of the study, hypothesized response rates are provided in 
Section 12.3.  In each case, a test that the response rate is less than or equal to the null 
hypothesis rate versus the response rate is greater than or equal to the alternative rate is 
being performed using the stopping rules provided.  Descriptive statistics will be used to 
describe the observed response rates at the dose used in the expanded cohorts for each of 
the arms.


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12.3.
Sample Size Determination
12.3.1.
Arm A: GSK3052230 + Paclitaxel + Carboplatin
An initial dose escalation will be used to establish the MTD (or MFD) for GSK3052230. 
Once the final dose is confirmed, at least 12 and up to 30 subjects in total will be enrolled 
at that dose, guided by decision rules defined in Section 4.2.1.  The assumptions 
underlying the design are detailed below and are based on the most recent phase 3 
evaluation of this regimen in NSCLC subjects including the squamous subset 
[Socinski, 2012].
The null hypothesis is:
H0: p≤25%
The alternative hypothesis is:
HA:p≥45%
Starting with a cohort of 12 subjects and allowing for a maximum sample size of 30, this 
design will have a type I error rate () of 0.11 and 86% power.  The trial is stopped early 
for futility if the predictive probability of success is less than 0.1%.  The Bayesian prior 
used in determining the design was Beta (0.3, 0.7), a relatively non-informative prior 
with a mean response rate of 30%.  Under the null hypothesis, the expected sample size is 
24.2 subjects and probability of early termination is 83.5%. Under the alternative 
hypothesis, the expected sample size is 29.7 subjects and the probability of early 
termination is 9%.
12.3.2.
Arm B: GSK3052230 + Docetaxel
An initial dose escalation will be used to establish the MTD. Once the final dose is 
confirmed, at least 14 and up to 30 subjects in total will be enrolled at that dose, using 
decision rules defined in Section 4.2.2.  The assumptions underlying the design are 
detailed below and are based on previously published randomized phase 3 data in the 2nd
line setting of metastatic NSCLC [Hanna, 2004]. 
The null hypothesis is:
H0: p≤10%
The alternative hypothesis is:
HA:p≥25%
Starting with a cohort of 14 subjects and allowing for a maximum sample size of 30, this 
design will have a type I error rate () of 0.07 and 79% power.  The trial is stopped early 
for futility if the predictive probability of success is less than 0.1%.  The Bayesian prior 
used in determining the design was Beta (0.15, 0.85), a relatively non-informative prior 
with a mean response rate of 15%.  Under the null hypothesis, the expected sample size is 


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24.0 subjects and probability of early termination is 84.5%. Under the alternative 
hypothesis, the expected sample size is 29.5 subjects and the probability of early 
termination is 12.2%.
12.3.3.
Arm C: GSK3052230 + Pemetrexed + Cisplatin
An initial dose escalation will be used to establish the MTD. Once the final dose is 
confirmed, at least 12 and up to 30 subjects in total will be enrolled at that dose, using 
decision rules defined in Section 4.2.3.  The assumptions underlying the design are 
detailed below and are based on previously published randomized phase 3 data in the 1st 
line setting of malignant pleural mesothelioma [Vogelzang, 2003].
The null hypothesis is:
H0: p≤40%
The alternative hypothesis is:
HA:p≥60%
Starting with a cohort of 12 subjects and allowing for a maximum sample size of 30, this 
design will have a type I error rate (α) of 0.10 and 82% power.  The trial is stopped early 
for futility if the predictive probability of success is less than 0.1%.  The Bayesian prior 
used in determining the design was Beta (0. 5, 0.5), a relatively non-informative prior 
with a mean response rate of 50%.  Under the null hypothesis, the expected sample size is 
23.1 subjects and probability of early termination is 86.4%. Under the alternative 
hypothesis, the expected sample size is 29.5 subjects and the probability of early 
termination is 13.7%.
12.4.
Sample Size Sensitivity
No analysis of sample size sensitivity was performed.
12.4.1.
Sample Size Re-estimation
Sample size re-estimation is not planned for this study.
12.5.
Data Analysis Considerations
12.5.1.
Analysis Populations
The All Treated Population is defined as all subjects who receive at least one dose of 
GSK3052230. Safety and anti-cancer activity will be evaluated based on this analysis 
population. 
The PK Population will consist of all subjects from the All Treated Population for whom 
a PK sample is obtained and analyzed.
The Assay Validation Population is defined as all subjects who were consented, 
screened for the study (regardless if the subject met eligibility requirements for study 


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enrollment) and whose tissue was assayed by the central laboratory for FGFR1
amplification.  Data from this population may be used for future validation of the assay.
12.6.
Treatment Comparisons
No statistical comparisons will be made between doses for a given study arm. Safety, PK, 
PD, biomarker, and anti-tumor activity summaries will be provided by dose level of 
GSK3052230 for each study arm.
12.7.
Interim Analysis
Preliminary safety data, including adverse events, changes in laboratory values and other 
safety parameters will be evaluated for each dose escalation cohort  prior to making dose 
escalation decisions.
For each study arm, after the initial 12 (Arms A and C) or 14 (Arm B) subjects have 
enrolled at the final dose, response data will be reviewed on an ongoing basis and the 
number of responses observed will be compared with the stopping rules provided in 
Section 4.2.1 (Arm A), Section 4.2.2 (Arm B), and Section 4.2.3 (Arm C). 
For Arm C only, the totality of the data will be reviewed prior to stopping for futility and 
the futility stopping rules are non-binding. The final analysis for Arm C will require 
16/30 responses as specified in Table 16. This is equivalent to a binomial test at the final 
analysis with alpha level 0.10 and power of 82%.
The rules for Parts A, B and C are also shown in a tabular format below:


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Table 14
Stopping Rules for Arm A: GSK3052230 + Paclitaxel + Carboplatin
Number of Patients Enrolled
This Number of Objective 
Responses to Stop Early for 
Futility
12
0
13
0
14
1
15
1
16
1
17
2
18
2
19
2
20
3
21
3
22
4
23
4
24
5
25
5
26
6
27
7
28
8
29
9
30
10


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Table 15
Stopping Rules for Arm B: GSK3052230 + Docetaxel
Number of Patients 
Enrolled
This Number of Objective 
Responses to Stop Early for 
Futility
14
0
15
0
16
0
17
0
18
0
19
0
20
0
21
0
22
1
23
1
24
1
25
1
26
2
27
2
28
3
29
4
30
5


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Table 16
Stopping Rules for Arm C: GSK3052230 + Pemetrexed + Cisplatin
Number of Patients 
Enrolled
This Number of Objective 
Responses to Stop Early for 
Futility
12
2
13
2
14
3
15
3
16
4
17
4
18
5
19
5
20
6
21
7
22
7
23
8
24
9
25
10
26
11
27
12
28
13
29
14
30
15
12.8.
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.


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12.8.1.
Anti-Cancer Activity Analyses
The All Treated Population will be used for anti-cancer activity analyses. Anti-cancer 
activity will be evaluated using RECIST, version 1.1 for Arms A and B and modified 
RECIST for Arm C. The response data will be summarized by study arm and dose level. 
Full details will be specified in the RAP. 
For the analysis of PFS, if the subject received subsequent anti-cancer therapy prior to the 
date of documented events, PFS will be censored at the last adequate assessment (e.g. 
assessment where visit level response is CR, PR, or SD) prior to the initiation of therapy. 
Otherwise, if the subject does not have a documented date of events, PFS will be 
censored at the date of the last adequate assessment.  Further details on rules for 
censoring will be provided in the RAP. PFS will be summarized using the Kaplan-Meier 
method.
12.8.2.
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, 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 RAP.
12.8.2.1.
Extent of Exposure
The number of subjects administered study treatment will be summarized according to 
the duration of therapy. 
12.8.2.2.
Adverse Events
AEs will be coded using the standard MedDRA and grouped by system organ class. AEs 
will be graded by the investigator according to the National Cancer Institute- Common 
Toxicity Criteria for Adverse Events (NCI-CTCAE), (version 4.03).
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, SAEs and AEs leading to discontinuation of study treatment. AEs, if listed 
in the NCI-CTCAE (version 4.03) will be summarized by the maximum grade.  
Otherwise, the AEs will be summarized by maximum intensity.
The incidence of deaths and the primary cause of death will be summarized.
For the dose-escalation portions of the study, dose-limiting toxicities (DLTs) will be 
listed for each subject and summarized by dose cohort according to International Data 
Standards Library standards. 
12.8.2.3.
Clinical Laboratory Evaluations
Hematology and clinical chemistry data will be summarized using frequencies and 
proportions according to National Cancer Institute-Common Toxicity Criteria for 


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Adverse Events (NCI-CTCAE) (version 4.03).  Laboratory test results outside the 
reference range that do not have an associated NCI-CTCAE criteria will be summarized 
using proportions. Further details will be provided in the Reporting and Analysis Plan 
(RAP).
12.8.2.4.
Other Safety Measures
Data for vital signs, ECGs, and ECHOs will be summarized based on predetermined 
criteria identified to be of potential clinical concern.  Immunogenicity data will be 
summarized and listed. Further details will be provided in the RAP.
12.8.3.
Patient Reported Outcomes
Change from baseline scores in LCSS and LCSS-meso will be calculated for all scales 
and timepoints. Change from baseline of 10mm was previously identified as clinically 
meaningful (P. Hollen, personal communication). The number of subjects achieving a 
10mm improvement at any timepoint will be tabulated for each component of the LCSS. 
For each component of the LCSS, plots of individual and/or mean/median values and 
change from baseline values over time will be produced.  If warranted, mixed-effects 
models may be used to model subject data over time for components of particular 
interest. Associations with efficacy assessments and between patient reported and 
clinician reported symptomatic will be explored when warranted. Further details will be 
provided in the RAP.
12.8.4.
Pharmacokinetic Analyses
PK analyses will be the responsibility of Clinical Pharmacokinetics/Modelling & 
Simulation, GSK. Plasma GSK3052230 concentration-time data may be combined with 
data from other studies and will be analyzed using a population pharmacokinetic 
approach.  A nonlinear mixed effects model will be used to determine population 
pharmacokinetic parameters (clearances, CL and volumes of distribution, V) and identify 
important covariates (e.g., age, weight, or disease related covariates).  Summary exposure 
measures (Cmax, AUC and average concentration Cav defined as time corrected AUC 
[AUC/]) will also be computed. Results of this analysis may be provided in a separate 
report.
Plasma concentration-time data will be listed and summarized using descriptive statistics 
(n, mean, SD, median, minimum and maximum).
12.8.5.
Pharmacokinetic/Pharmacodynamic Analyses
Observed or predicted concentrations or summary exposure measure (eg; Cmax, Ctrough, 
and Cav) may be combined with safety and efficacy pharmacodynamic measures of 
interest to examine potential exposure response relationships.  Graphical evaluation will 
first be performed. 
Where evidence of activity is seen, linear and/or non-linear mixed effect models may be 
fitted to the data to estimate PK/PD parameters of interest (e.g. slope, baseline (E0), 
concentration for 50% of maximum effect (EC50) and maximum effect (Emax)).


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Overall efficacy data, as assessed by conventional RECIST 1.1 criteria (best confirmed 
response) and overall tumor burden, may be described using ordered categorical model 
and continuous models with summary exposure parameters (eg; Cmax, Ctrough, and 
Cav) as covariates derived from the population PK analysis.  Further model details will 
be provided in the Reporting and Analysis Plan.
12.8.6.
Tumor Kinetics Analysis
Data from some arms of the study may be combined to describe the kinetics of tumor 
growth based on the sum of longest diameters and/or volume of target lesions. 
The kinetics of tumor growth may be described as a function of time using the NSCLC 
model described by the FDA [Wang, 2009]. The tumor size (TS) is expressed as:
TS(t) = BSL•e-SRt + PR•t
where TS(t) denotes the tumor size measured as the sum of longest distance (mm) of 
lesions or volume (mm3) at time t, BSL is the baseline tumor size, SR is the exponential 
tumor shrinkage rate constant and PR is the linear tumor progression rate.
The kinetics of tumor growth may also be described as a function of time using the model 
described by Claret [Claret, 2009]. The model is expressed as:
dTS(t)/dt = (KL-KD•e-t)•TS(t)
where TS(t) denotes the sum of longest distance (mm) of lesions or volume (mm3) at 
time t, with TS(0) being the baseline tumor size, KL represents the exponential tumor 
growth rate, KD represents the exponential rate of tumor shrinkage (i.e. drug effect on 
total tumor size), λ is the rate constant for drug resistance/disease progression.  A 
measure of exposure of one or more of the administered medications may be included in 
the models.
The equation proposed by Wang and/or Claret will be fit to the observed data using a 
mixed-effects model with NONMEM VII.  Other models of the kinetics of tumor growth, 
such as a 2-parameter model, may be used to analyze the data [Stein, 2011; Stein, 2012].
The time to tumor growth (TTG) may be estimated with parameters from the appropriate 
model. Subject characteristics such as baseline tumor size, performance status, LDH, age, 
sex, race, prior therapies, or radiotherapy, may be evaluated to determine which 
covariates have a significant effect on the kinetics of tumor growth.
12.8.7.
Translational Research Analyses
Exploratory analysis may be performed to examine potential relationships between 
anticancer activity and changes in markers of deregulation of FGF signaling pathway 
(example: FGFR1 gene amplification) or tumor biology (e.g. cytokines, acute phase 
proteins, relevant transcripts and/or proteins) or between anticancer activity and potential 
markers of sensitivity.


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The results of translational research investigations may be reported separately from the 
main clinical study report or as an amendment.  All endpoints of interest from all 
comparisons will be descriptively and/or graphically summarized as appropriate to the 
data. Further details on the translational research analyses will be addressed in the RAP.
12.8.8.
Pharmacogenetic Analyses
Further details on pharmacogenetic (PGx) analyses will be addressed in Appendix 1 and 
the PGx Reporting and Analysis Plan (RAP).
13.
STUDY CONDUCT CONSIDERATIONS
13.1.
Posting of Information on Clinicaltrials.gov
Study information from this protocol will be posted on publicly available clinical trial 
registers before enrollment of subjects begins.
13.2.
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.
13.3.
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.


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The Sponsor will work with the investigator to ensure the Institutional review board 
(IRB)/ethics committee (EC) is notified.
13.4.
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 eCRF will serve as the source document.
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.
13.5.
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.
13.6.
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 


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(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 SPM.
13.7.
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.
13.8.
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.


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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 8 
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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14.
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15.
APPENDICES
15.1.
Appendix 1: Pharmacogenetics (PGx)
PGx Research
PGx – Background
Pharmacogenetics (PGx) is the study of variability in drug response due to hereditary 
factors in different populations. There is increasing evidence that an individual's genetic 
composition (i.e., genotype) may impact the pharmacokinetics (PK) (absorption, 
distribution, metabolism, and elimination), pharmacodynamics (PD) (relationship 
between concentrations and pharmacologic effects or the time course of pharmacologic 
effects) and/or clinical outcome (in terms of efficacy and/or safety and tolerability). Some 
reported examples of PGx associations with safety/adverse events include:
Drug
Disease
Gene
Outcome
Abacavir
HIV
[Hetherington, 2002; 
Mallal, 2002]
Human 
Leukocyte 
Antigen B (HLA-
B*5701)
Individuals with HLA-B*5701 variant may be at 
increased risk for experiencing hypersensitivity to 
abacavir. Clinical assays are available for HLA-B*5701 
but none has been validated. HLA-B*5701 screening 
would supplement but never replace abacavir clinical 
risk management strategies aimed at minimizing rare 
but serious outcomes associated with abacavir 
hypersensitivity
Carbamazepine
Seizure, Bipolar 
disorders & 
Analgesia 
Chung, 2010; 
Ferrell, 2008.
HLA-B*1502
Independent studies indicated that patients of East 
Asian ancestry who carry HLA-B*1502 are at higher risk 
of Stevens-Johnson Syndrome and toxic epidermal 
necrolysis. Regulators, including the US FDA and the 
Taiwanese TFDA, have updated the carbamazepine 
drug label to indicate that patients with ancestry in 
genetically at risk populations should be screened for 
the presence of HLA-B*1502 prior to initiating treatment 
with carbamazepine.
Warfarin
Cardiovascular
[Neergard, 2006;
Wilke, 2005]
CYP2C9
SAEs experienced by some subjects on warfarin may 
be explained by variations in the CYP2C9 gene that 
influences the degree of anticoagulation achieved.
Irinotecan
Cancer
FDA News Release, 
2005
UGT1A1
Variations in the UGT1A1 gene can influence a 
patient’s ability to break down irinotecan, which can 
lead to increased blood levels of the drug and a higher 
risk of side effects. A dose of irinotecan that is safe for 
one patient with a particular UGT1A1 gene variation 
might be too high for another subject without this 
variation, raising the risk of certain side effectsA genetic 
blood test (Invader UGT1A1molecular assay) is 
available that can detect variations in the gene.
A key component to successful PGx research is the collection of samples during the 
conduct of clinical studies.


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Collection of whole blood, may enable PGx analysis to be conducted if at any time it 
appears that there is a potential unexpected or unexplained variation in handling or 
response to GSK3052230.
PGx Research Objectives
The objective of the PGx research (if there is a potential unexpected or unexplained 
variation) is to investigate a possible genetic relationship to handling or response to 
GSK3052230. If at any time it appears there is potential variability in response in this 
clinical study or in a series of clinical studies with GSK3052230 that may be attributable 
to genetic variations of subjects, the following objectives may be investigated:

Relationship between genetic variants and the PK and/or PD of study treatment

Relationship between genetic variants and safety and/or tolerability of study 
treatment

Relationship between genetic variants and efficacy of study treatment.
Study Population
Any subject who has given informed consent to participate in the clinical study, has met 
all the entry criteria for the clinical study, and receives study treatment may take part in 
the PGx research. Any subject who has received an allogeneic bone marrow transplant 
must be excluded from the PGx research.
Subject participation in the PGx 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.
Study Assessments and Procedures
In addition to any blood samples taken for the clinical study, a whole blood sample 
(~6 mL) will be collected for the PGx research using a tube containing EDTA. It is 
recommended that the blood sample be taken at the first opportunity after a subject has 
been randomized and provided informed consent for PGx research, but may be taken at 
any time while the subject is participating in the clinical study.
The PGx sample is labeled (or “coded”) with a study specific number that can be traced 
or linked back to the subject only by the investigator or site staff. Coded samples do not 
carry personal identifiers (such as name or social security number). The blood sample is 
taken on a single occasion unless a duplicate sample is required due to inability to utilize 
the original sample. 
The DNA extracted from the blood sample may be subjected to sample quality control 
analysis. This analysis will involve the genotyping of several genetic markers to confirm 
the integrity of individual samples. If inconsistencies are noted in the analysis, then those 
samples may be destroyed. 


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The need to conduct PGx analysis may be identified after a study (or set of studies) of 
GSK3052230 has been completed and the study data reviewed. In some cases, the 
samples may not be studied. e.g., no questions are raised about how people respond to 
GSK3052230. 
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 use samples collected from the study for the 
purpose stated in this protocol and in the informed consent form. 
Subjects can request their sample to be destroyed at any time.
Subject Withdrawal from Study
If a subject who has consented to participate in PGx research and has a sample taken for 
PGx research withdraws from the clinical study for any reason other than lost to follow-
up, the subject will be given the following options:

The sample is retained for PGx research.

Any PGx sample is destroyed.
If a subject withdraws consent from the PGx 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. In either case, GSK will only keep study 
information collected/generated up to that point.
Screen and Baseline Failures
If a blood sample for PGx research has been collected and it is determined that the 
subject does not meet the entry criteria for participation in the clinical study, then 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.
PGx Analyses
The aim of pharmacogenetic analyses will be to investigate the relationship between 
genetic variations in germline DNA and response to study treatment. The specific type of 
genetic investigation to be applied will be dependent on the most scientifically feasible 
approach available to address understanding of the response to the study treatment.
Generally, two approaches may be utilized to explore the association of genetic variation.
1.
Candidate gene analysis where variations in specific genes may be studied that 
encode the drug target, or drug mechanism of action pathways, drug metabolizing 
enzymes, drug transporters or which may underpin adverse events, disease risk or 
drug response.


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These candidate genes that may be investigated in this study include the following: the 
GSK Absorption, Distribution, Metabolism and Excretion genes. These play a central 
role in drug PK and PD.  In addition, continuing research may identify other enzymes, 
transporters, proteins, or receptors that may be involved in response to GSK3052230. The 
genes that may code for these proteins may also be studied.
2.
Genome-wide scans involving a large number of polymorphic markers (e.g., single 
nucleotide polymorphisms) located throughout the genome. This approach is often 
employed when potential genetic effects are not well understood.
The results of PGx investigations will be reported either as part of the main clinical study 
report or as a separate report. All endpoints of interest from all comparisons will be 
descriptively and/or graphically summarized as appropriate to the data. In all cases, 
appropriate statistical methods will be used to analyze the genetic markers in the context 
of other clinical data. Statistical methods may include, but are not limited to Hardy-
Weinberg Equilibrium testing, Comparison of Demographic and Baseline Characteristics 
by Genotype, Evaluation of Genotypic Effects, Evaluation of Treatment by Genotype and 
Gene-Gene Interaction, Linkage Disequilibrium, Multiple Comparison and Multiplicity 
and/or Power and Sample Size Considerations A detailed description of the analyses to 
be performed will be documented in the pharmacogenetics RAP.
Informed Consent
Subjects who do not wish to participate in the PGx research may still participate in the 
clinical study. PGx informed consent must be obtained prior to any blood being taken for 
PGx research.
Provision of Study Results and Confidentiality of Subject’s PGx Data
GSK may summarize the cumulative PGx research results in the clinical study report,.
In general, GSK does not inform the investigator, subject or anyone else (e.g., family 
members, study investigators, primary care physicians, insurers, or employers) of the 
PGx research results unless required by law. The information generated from PGx 
research is preliminary in nature, and the significance and scientific validity of the results 
are undetermined at such an early stage of research. 


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References
Chung WH, Hung SL, Chen YT. Genetic predisposition of life-threatening antiepileptic-
induced skin reactions. Expert Opin. Drug Saf. 2010; 9: 15-21.
Ferrell PB, McLeod HL. Carbamazepine, HLA-B*1502 and risk of Stevens-Johnson 
syndrome and toxic epidermal necrolysis: US FDA recommendations. 
Pharmacogenomics. 2008; 9: 1543-46.
Hetherington S, Hughes AR, Mosteller M, Shortino D, Baker KL, Spreen W, Lai E, 
Davies K, Handley A, Dow DJ, Fling ME, Stocum M, Bowman C, Thurmond LM, Roses 
AD. Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. 
Lancet. 2002; 359:1121-2.
Mallal S, Nolan D, Witt C, Masel G, Martin AM, Moore C, Sayer D, Castley A, Mamotte 
C, Maxwell D, James I. Association between presence of HLA-B*5701, HLA-DR7, and 
HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet. 
2002; 359:727-32.
Neergard. Reducing the risk of blood thinners. Associated press, September 2006. 
U.S. Food and Drug Administration, FDA Clears Genetic Test That Advances 
Personalized Medicine Test Helps Determine Safety of Drug Therapy 22 August 2005, 
http://www.fda.gov/bbs/topics/NEWS/2005/NEW01220.html
Wilke RA, Musana AK, Weber WW. Cytochrome P450 gene-based drug prescribing, 
and factors impacting translation into routine clinical practice. Personalized Med 2005; 2: 
213–224.


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15.2.
Appendix 2: 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.


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15.3.
Appendix 3: COCKCROFT-GAULT FORMULA
ClCr (mL/min) = 
Q x (140 - age[yr]) x ideal body weight [kg]*
72 x serum creatinine [mg/dL]
Q = 0.85 for females
Q = 1.0 for males
OR
ClCr (mL/min) = 
K x (140 - age[yr]) x ideal body weight [kg]*
Serum creatinine [umol/L]
K = 1.0 for females 
K = 1.23 for males
*Calculation of Ideal Body Weight Using the Devine Formula [Devine, 1974]
Ideal body weight:
Males = 
50.0 kg + (2.3 kg x each inch over 5 feet) or 50.0 kg + (0.906 kg x each cm over 
152.4 cm)
Females = 
45.5 kg + (2.3 kg x each inch over 5 feet) or 45.5 kg + (0.906 kg x each cm over 
152.4 cm)
Example:
Male, actual body weight = 90.0 kg, height = 68 inches
Ideal body weight = 50.0 + (2.3) (68-60) = 68.4 kg.


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15.4.
Appendix 4: ECOG Performance Status1
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are 
protected by third party copyright laws and therefore have been excluded.


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15.5.
Appendix 5: Liver Chemistry Monitoring, Interruption 
Stopping and Follow-up Criteria


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15.6.
Appendix 6: 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 
[Xin, 2004] [NKF Guidelines, 2002]


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15.7.
Appendix 7: Country Specific Requirements
France or UK:
French or UK Specific QTc Stopping Criteria:
In line with local requirements, French subjects that meet the criteria QTc1 below will 
have GSK3502230 withheld:
QTcB > 500 msec
In line with local requirements, UK subjects that meet the criteria QTc1 below will have 
study treatment withheld:
QTc > 500 msec
1Based on average corrected QT (QTc) interval value of triplicate electrocardiograms 
(ECGs) to include manual over-read. For example, if an ECG demonstrates a prolonged 
QT interval, obtain 2 more ECGs over a brief period, and then use the averaged QTc 
values of the 3 ECGs to determine whether the subjects should have GSK3502230 
withheld.
QT interval (corrected for HR) ≥500 msec; GSK3502230 will be permanently 
discontinued.
QTc interval increase from baseline ≥ 60 msec and maximum QTc  < 500 msec; 
GSK3502230 may be restarted at a reduced dose level after discussion with the medical 
monitor once the QTc returns to baseline.  If QTc prolongation meeting stopping criteria 
recurs after re-challenge, GSK3502230 must be permanently discontinued.
If the QTc prolongation resolves to Grade 1 or baseline, the subject may be re-started on 
GSK3502230 if the investigator and GSK Medical Monitor agree that the subject will 
benefit from further treatment.
No other known country specific requirements are currently required.


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15.8.
Appendix 8: Protocol Amendment Changes
Amendment 5
Where the Amendment Applies
This amendment applies to all sites.
Summary of Amendment Changes with Rationale
Amendment 5 updates the GSK medical physician contacts for safety questions.  The 
synopsis is being clarified to be consistent with the changes in Amendment 4 
regarding histologically or cytologically confirmed diagnosis being Stage IIIB or IV 
for subjects in Arm A or B.  Additionl wording as been provided regarding cisplatin
dosing and hydration practices to clarify this should be per local standards.  The 
FGF117360 study team has been providing updates and information on infusion 
reactions during the program.  The team has been monitoring GSK3052230 related 
dosing events and have added guidance for pre-medication per local standards if an 
infusion reaction is observed.  The GSK3052230 infusion time should be extended 
from 30 minutes to 60 minutes if initial reaction is observed or up to 90 minutes if a 
second reaction is observed.  This guidance in dosing was based on joint discussions 
between investigators and GSK team to determine most appropriate path forward for 
these subjects.  The Time and Event schedule has been modified to allow more 
flexible screening timing for subjects in Arm A who desire to start chemotherapy 
prior to GSK3052230 initial dose.   The Time and Event schedule for 
pharmacokinetics has been modified to include cisplatin sampling for subjects in 
Arm C.  Finally, in the United Kindgom at selected sites total calcium would be 
utilized instead of monitoring for both total calcium and ionized calcium.  At this 
point in time, there has been no safety signals observed in any arms regarding 
calcium assessments.
List of Specific Changes
CHANGE 1: Medical monitor contact information
PREVIOUS TEXT:
Role
Name
Day Time 
Phone 
Number
After-hours 
Phone/Cell/
Pager 
Number
Fax 
Number
GSK Address
Medical 
Monitor
MD
GlaxoSmithKline
1250 South Collegeville Road
PO Box 5089
Collegeville, PA 19426
Email:
PPD
PPD
PPD
PPD
PPD


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Medical 
Monitor
MD
GlaxoSmithKline
1250 South Collegeville Road
PO Box 5089
Collegeville, PA 19426
Email:
Additional medical monitor or sponsor contacts may be provided in a letter to investigator during the course 
of the study conduct without involving a protocol amendment.  
NEW TEXT:
(new text bold and underlined, deleted text in strikethrough)
Role
Name
Day Time 
Phone 
Number
After-hours 
Phone/Cell/
Pager 
Number
Fax 
Number
GSK Address
Medical 
Monitor
MD
GlaxoSmithKline
1250 South Collegeville Road
PO Box 5089
Collegeville, PA 19426
Email:
Medical 
Monitor
MD, PhD
GlaxoSmithKline
1250 South Collegeville Road
PO Box 5089
Collegeville, PA 19426-0989, 
United States
Email: 
Secondary 
Medical 
Monitor
MD
GlaxoSmithKline
1250 S. Collegeville Road, 
Collegeville, PA 19426-0989, 
United States
Email:  
Additional medical monitor or sponsor contacts may be provided in a letter to investigator during the course 
of the study conduct without involving a protocol amendment.  
CHANGE 2: Clarifications to be consistent with previous amendments
PREVIOUS TEXT, Synopsis:
Rationale for change: This was modified was made in Amendment 4 changes and body of 
protocol but not in synopsis.  This change is to ensure consistency within protocol.
1. Histologically or cytologically confirmed diagnosis:
Arms A and B: Stage IV or recurrent metastatic squamous NSCLC (TNM Staging 
for NSCLC, 7th Edition) with FGFR1 gene amplification by central laboratory 
testing.
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


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NEW TEXT, Synopsis:
(new text bold and underlined, deleted text in strikethrough)
1. Histologically or cytologically confirmed diagnosis:
Arms A and B: Stage IIIB or IV or recurrent metastatic squamous NSCLC (TNM 
Staging for NSCLC, 7th Edition) with FGFR1 gene amplification by central 
laboratory testing.
Rationale for change: This was modified was made in Amendment 4 changes but not 
within the text.  This change is to ensure consistency within protocol.
NEW TEXT, Sectino 1.4.1.1. Preclinical data on GSK3052230
Added reference [DeYoung, 2014].
Which was updated in REFERENCES, Section 14
DeYoung MP, Shenk C, Bleam M, Barnette M, Ganji G, Hoang B, Tunstead J, 
Bellovin D, Los G, Minthorn E, Kumar R. Preclinical efficacy of targeting FGF 
autocrince signaling in mesothelioma with the FGF ligand trap, FP-
1039/GSK3052230.  AACR 2014.
PREVIOUS TEXT, Section 3.2.1, Inclusion criteria:
Availability of archival tumor tissue required for assessment of deregulated FGF pathway 
signaling eg, FGFR1 amplification or FGF2 expression.
NEW TEXT, Section 3.2.1, Inclusion criteria:
Availability of archival tumor tissue required for assessment of deregulated FGF pathway 
signaling eg, FGFR1 amplification or FGF2 or FGFR1 expression.
Change 3: Chemotherapy treatment per local standards
NEW TEXT, Section 4.1.
Subjects on pemetrexed/cisplatin may have their cisplatin stopped after 4 cycles per 
local clinical standards.
NEW TEXT, Section 4.5.4.

1-2 liters of fluid infused for 8-12 hours prior to cisplatin dose (or hydration per 
local standard)
CHANGE 4: Infusion Reactions and dosing timings
PREVIOUS TEXT, Exclusion criteria, Section 1.6, Summary of Risk Management: 
If infusion reactions are noted in subjects not already premedicated with glucocorticoids, 
antihistamines and H2 receptor antagonists, appropriate premedication against 


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hypersensitivity reactions may be initiated prior to the next infusions at the discretion of 
the investigator according to the institution’s standard practice.  
NEW TEXT, Exclusion criteria, Section 1.6, Summary of Risk Management:
(new text bold and underlined, deleted text in strikethrough)
If infusion reactions are noted in subjects not already premedicated with glucocorticoids, 
antihistamines and H2 receptor antagonists, appropriate premedication against 
hypersensitivity reactions may be initiated prior to the next infusions at the discretion of 
the investigator according to the institution’s standard practice.  All subjects who have 
experienced an infusion reaction should have GSK3052230 infused over 60 minutes 
instead of 30 minutes and pre-treated with appropriate local pretreatment 
guidelines. If the subject continues to have a reaction on re-challenge, the infusion of 
GSK3052230 may be prolonged for 90 minutes”
NEW TEXT, Section 4.7.4 GSK3052230 Dose Modification
4.7.4.1
GSK3052230 Dose Modifications regarding infusion related 
reactions
Subjects should be closely monitored for GSK3052230 infusion-related reactions. 
All subjects who have experienced an infusion reaction due to GSK3052230 (and 
not chemotherapy) should have GSK3052230 infused over 60 minutes instead of 30 
minutes and pre-treated with appropriate local instituationl pre-treatment 
guidelines (example: medications such as steroids, antihistamines, acetaminophen, 
H-2 antagonists, and antiemetics, according to local pretreatment guidelines). If the 
subject continues to have a reaction on re-challenge the infusion of GSK3052230 
may be prolonged to 90 minutes. Epinephrine for subcutaneous injection, 
diphenhydramine for IV injection, and any other medications and resuscitation
equipment for the emergency management of anaphylactic reactions should be 
quickly available subject infusions.


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CHANGE 5: Time and Events Screening Window for Arm A subjects
PREVIOUS TEXT, Section 7 Study Assessments and Procedures:
Table 10
Time and Events Schedule
Time and Events Schedule for FGF117360
Screen
Cycle 1
Cycle 2
Additional Cycles
Every 4 
Cycles, 
D1
EOT
30 
day 
F/U
D1
D8
D9
D15
D1
D8
D15
D1
D8
D15
Visit Window
Once the subject provides consent, a tumor sample may be submitted for Arms A and B for FGFR1 amplification at any time (there is no time limit or 
window).  All other screening assessments should be conducted within 30 days of C1D1. Visit windows of ±2 days during study through EOT, +7 days 
for F/U.
Ophthalmologic Exam
To be performed by ophthalmologist or qualified 
optometrist.
X
Perform assessment if subject discontinues prior to C4.
C4 only
ECHO
Perform at EOT if subject discontinues prior to 
C4. Visit windows of ±7 days during study.
X
C4 only
early 
disc
Forced Vital Capacity
Assess D1 of every odd cycle, Arm C only, Visit 
windows of ±7 days days during study.
X
X
Odd
X


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REVISED TEXT, Section 7 Study Assessments and Procedures:
(new text bold and underlined, deleted text in strikethrough)
Table 10
Time and Events Schedule
Time and Events Schedule for FGF117360
Screen
Cycle 1
Cycle 2
Additional Cycles
Every 4 
Cycles, 
D1
EOT
30 
day 
F/U
D1
D8
D9
D15
D1
D8
D15
D1
D8
D15
Visit Window
Once the subject provides consent, a tumor sample may be submitted for Arms A and B for FGFR1 amplification at any time (there is no time limit or 
window).  All other screening assessments should be conducted within 30 days of C1D1. Visit windows of ±2 days during study through EOT, +7 days 
for F/U. For Arm A subjects who wish to start chemotherapy prior to GSK3052230 screening period is 30 days +3 to allow baseline imaging 
scans to be performed prior to chemotherapy but within 30+3days of GSK3052230 first dose.
Rationale for change: This was modified was made in Amendment 4 changes but not within the text.  This change is to ensure consistency 
within protocol regarding opthalmoligic exams.
Ophthalmologic Exam
To be performed by ophthalmologist or qualified 
optometrist. (Visit windows of ±7 days post 
baseline).
X
Perform assessment if subject discontinues prior to C4.
C4 
only
ECHO
Perform at EOT if subject discontinues prior to 
C4. Visit windows of ±7 days during study post 
baseline.
X
C4 
only
early 
disc
Forced Vital Capacity
Assess D1 of every odd cycle, Arm C only, Visit 
windows of ±7 days during study post baseline.
X
X
Odd
X


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CHANGE 6: Time and Events PK Sampling for Cisplatin in Arm C subjects
PREVISION TEXT, Section 7: Table 11
Pharmacokinetic Sampling Schedule
FGF117360 Pharmacokinetic Sampling Schedule
Limited PK
Extensive PK
Extensive PK
Extensive PK
Time 
When
Window
Arm A
Arm B
Arm C
n=20pts in each arm 
n>=10pts
n>=10pts
n>=10pts
Cycle 2 Day 1
Prior to infusion of 
GSK3052230
Up to 12 hr prior to infusion of 
GSK3052230
GSK3052230 PK
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 PK
End of infusion of 
GSK3052230
Up to 5 min prior to end of 
infusion of GSK3052230
GSK3052230 PK
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 PK
1 hr after start of paclitaxel 
infusion or end of 
docetaxel or pemetrexed 
infusion
10 min for paclitaxel or up to 
5 min prior to end of docetaxel 
infusion or up to 1 min prior to 
end of pemetrexed infusion
GSK3052230 
PK
Paclitaxel PK
GSK3052230 
PK
Docetaxel PK
GSK3052230 PK
Pemetrexed PK
1 hr after end of 
pemetrexed infusion
20 min
Pemetrexed PK
End of paclitaxel infusion 
or 2 hr after end of 
docetaxel or pemetrexed 
infusion
up to 5 min prior to end of 
paclitaxel infusion or 20 min 
for docetaxel and pemetrexed 
Paclitaxel PK
Docetaxel PK
Pemetrexed PK
2 hr after end of paclitaxel 
infusion or 5 hr after end 
of docetaxel or 
pemetrexed infusion
30 min
(selected sites)
GSK3052230 
PK
Paclitaxel PK
(selected sites)
GSK3052230 
PK
Docetaxel PK
(selected sites)
GSK3052230 PK
Pemetrexed PK
REVISED TEXT, Section 7: Table 11
Pharmacokinetic Sampling Schedule
FGF117360 Pharmacokinetic Sampling Schedule
Limited PK
Extensive PK
Extensive PK
Extensive PK
Time 
When
Window
Arm A
Arm B
Arm C
n=20pts in each arm 
n>=10pts
n>=10pts
n>=10pts
Cycle 2 Day 1
Prior to infusion of 
GSK3052230
Up to 12 hr prior to infusion of 
GSK3052230
GSK3052230 PK
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 PK
End of infusion of 
GSK3052230
Up to 5 min prior to end of 
infusion of GSK3052230
GSK3052230 PK
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 PK


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FGF117360 Pharmacokinetic Sampling Schedule
Limited PK
Extensive PK
Extensive PK
Extensive PK
Time 
When
Window
Arm A
Arm B
Arm C
1 hr after start of paclitaxel 
infusion or end of 
docetaxel or pemetrexed 
infusion
10 min for paclitaxel or up to 
5 min prior to end of docetaxel 
infusion or up to 1 min prior to 
end of pemetrexed infusion
GSK3052230 
PK
Paclitaxel PK
GSK3052230 
PK
Docetaxel PK
GSK3052230 PK
Pemetrexed PK
Cisplatin PK
1 hr after end of 
pemetrexed infusion
20 min
Pemetrexed PK
Cisplatin PK
End of paclitaxel infusion 
or 2 hr after end of 
docetaxel or pemetrexed 
infusion
up to 5 min prior to end of 
paclitaxel infusion or 20 min 
for docetaxel and pemetrexed 
Paclitaxel PK
Docetaxel PK
Pemetrexed PK
Cisplatin PK
2 hr after end of paclitaxel 
infusion or 5 hr after end 
of docetaxel or 
pemetrexed infusion
30 min
(selected sites)
GSK3052230 
PK
Paclitaxel PK
(selected sites)
GSK3052230 
PK
Docetaxel PK
(selected sites)
GSK3052230 PK
Pemetrexed PK
Cisplatin PK


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CHANGE 7: Ionized Calcium monitoring for sites in United Kingdom
PREVIOUS TEXT, Section 7.3.8 Laboratory Assessments::
Table 12
List of Clinical Laboratory Tests
Hematology
Platelet Count
Automated WBC Differential:
Red blood cell (RBC) Count
Neutrophils (absolute)
White blood cell (WBC) Count 
(absolute) 
Lymphocytes (absolute)
Hemoglobin
Monocytes (absolute)
Eosinophils (absolute)
Basophils (absolute)
Clinical Chemistry
Potassium, Sodium, Chloride, Total carbon dioxide, total Calcium, ionized calcium, magnesium, phosphate, 
albumin, glucose (fasting),
REVISED TEXT, Section 7.3.8 Laboratory Assessments:
(new text bold and underlined, deleted text in strikethrough)
Table 12
List of Clinical Laboratory Tests
Hematology
Platelet Count
Automated WBC Differential:
Red blood cell (RBC) Count
Neutrophils (absolute)
White blood cell (WBC) Count 
(absolute) 
Lymphocytes (absolute)
Hemoglobin
Monocytes (absolute)
Eosinophils (absolute)
Basophils (absolute)
Clinical Chemistry
Potassium, Sodium, Chloride, Total carbon dioxide, total Calcium, ionized calcium*, magnesium, 
phosphate, albumin, glucose (fasting),
*Ionized calcium collected may not be collected in some selected sites and only total calcium is 
collected for subjects regarding safety monitoring.


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Amendment 4
Where the Amendment Applies
This amendment applies to all sites.
Summary of Amendment Changes with Rationale
The protocol medical monitor contact information was updated and information will be 
provided during the study to prevent protocol amendments if there are staff changes.  In 
addition, based on investigator feedback, some sections of the protocol needed further 
clarification or broader assessment windows for subject assessments.  Therefore 
additional information on preclinical studies in mesothelioma was added in the 
background section, and clarifications were provided for modified RECIST, the time & 
event tables, concomitant medications and Cockcroft-gault formula description.
We have expanded the lines of treatment to address the changing parameters in the 
NSCLC development and treatments.  We have broadened the lines of therapy to allow 
for additional subjects to benefit from GSK3052230 in combination with chemotherapy.  
In addition, the mechanism of resistance for current FGF inhibitors may be different from 
GSK3052230 and therefore those who previously failed FGFR inhibitor treatment will be 
included.
The protocol was expanded to allow intra-subject dose escalation or de-escalation.  This 
allows subjects who receive benefit during the dose escalation to transition to the 
recommended expansion dose.  In addition, additional wording has been added to allow 
alternative dosing and schedules to be explored.  Example, if a MTD is not obtained the 
study could explore lower doses or MFD levels based on the totality of the data (eg, 
safety, pharmacokinetics, pharmacodynamics, etc).  
List of Specific Changes
CHANGE 1: Medical monitor contact information
PREVIOUS TEXT:
Role
Name
Day Time 
Phone 
Number
After-hours 
Phone/Cell/
Pager 
Number
Fax 
Number
GSK Address
Primary 
Medical 
Monitor
 
MD
GlaxoSmithKline
1250 South Collegeville Road
PO Box 5089
Collegeville, PA 19426
Email: 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


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Role
Name
Day Time 
Phone 
Number
After-hours 
Phone/Cell/
Pager 
Number
Fax 
Number
GSK Address
Secondary 
Medical 
Monitor
 
 
MD
GlaxoSmithKline
Five Moore Drive,
Mailstop 17.2225.2B
Research Triangle Park, NC 
27709
Email: 
NEW TEXT:
(new text bold and underlined, deleted text in strikethrough)
Role
Name
Day Time 
Phone 
Number
After-hours 
Phone/Cell/
Pager 
Number
Fax 
Number
GSK Address
Primary 
Medical 
Monitor
 
MD
GlaxoSmithKline
1250 South Collegeville Road
PO Box 5089
Collegeville, PA 19426
Email: 
Secondary 
Medical 
Monitor
 
 
MD
GlaxoSmithKline
Five Moore Drive,
Mailstop 17.2225.2B
Research Triangle Park, NC 
27709
Email: 
Medical 
Monitor
 
MD
GlaxoSmithKline
1250 South Collegeville Road
PO Box 5089
Collegeville, PA 19426
Email:
Medical 
Monitor
MD
GlaxoSmithKline
1250 South Collegeville Road
PO Box 5089
Collegeville, PA 19426
Email:
Additional medical monitor or sponsor contacts may be provided in a letter to investigator during 
the course of the study conduct without involving a protocol amendment.  
PP
DPPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PP
DPPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


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CHANGE 2: Abbreviations 
(new text bold and underlined, deleted text in strikethrough)
NEW TEXT:
TGI
tumor growth inhibition 
CHANGE 3: Study Design 
(new text bold and underlined, deleted text in strikethrough)
PREVIOUS TEXT:
Study Design: This will be a multi-arm, multicenter, non-randomized, parallel-
group, uncontrolled, open-label Phase IB study designed to evaluate the safety, 
tolerability and preliminary activity of GSK3052230 in combination with 
paclitaxel + carboplatin in previously untreated metastatic squamous NSCLC 
(Arm A), in combination with docetaxel in metastatic squamous NSCLC that has 
progressed after 1 line of chemotherapy (Arm B), or in combination with 
pemetrexed + cisplatin in MPM previously untreated with chemotherapy or 
investigational agents (Arm C). 
REVISED TEXT:
Study Design: This will be a multi-arm, multicenter, non-randomized, parallel-
group, uncontrolled, open-label Phase IB study designed to evaluate the safety, 
tolerability and preliminary activity of GSK3052230 in combination with 
paclitaxel + carboplatin in previously untreated metastatic squamous NSCLC 
(Arm A), in combination with docetaxel in metastatic squamous NSCLC that has 
progressed after at least 1 line of chemotherapy (Arm B), or in combination with 
pemetrexed + cisplatin in MPM previously untreated with chemotherapy or 
investigational agents (Arm C). 
CHANGE 4: Exploratory Endpoints and Objectives 
(new text bold and underlined, deleted text in strikethrough)
Section Summary
PREVIOUS TEXT:
Objectives and Endpoints:
The primary objectives and endpoints are noted below. The full objectives and 
endpoints (primary, secondary and translational) are located in the main protocol 
in Section 2.


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REVISED TEXT:
Objectives and Endpoints:
The primary objectives and endpoints are noted below. The full objectives and 
endpoints (primary, secondary and translational exploratory) are located in the 
main protocol in Section 2.
Section: 2.3 Exploratory
PREVIOUS TEXT:
Objectives
Exploratory
To develop and validate a Fluorescence 
in situ hybridization (FISH) -based 
assay to measure FGFR1 gene 
amplification status..
Endpoint
Exploratory
Identification and validation of 
alternative measures of FGF signaling 
pathway deregulation retrospectively 
(eg, FGF2 overexpression) as predictive 
biomarkers for subject selection and 
potential development of a companion 
diagnostic
REVISED TEXT:
Objectives
Exploratory
To develop and validate an assay to 
measure of  FGFR1 gene 
amplification status such as, but not 
limited to, a Fluorescence in situ
hybridization (FISH) -based assay to 
measure FGFR1 gene amplification 
status.
Endpoint
Exploratory
Identification and validation of 
alternative measures of FGF signaling 
pathway deregulation retrospectively
such as ligand or receptor 
overexpression for example but not 
limited to FGF2 or FGFR1 expression  
FGF2 overexpression as predictive 
biomarkers for subject selection and 
potential development of a companion 
diagnostic


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CHANGE 5: Number of subjects
(new text bold and underlined, deleted text in strikethrough)
Section: Summary
NEW TEXT, Summary section:
Number of Subjects: Approximately 70 subjects (minimum of 38 and up to 120, 
alternative dosing cohorts could potentially add another ~6 to ~40 subjects).
NEW TEXT, Section 3.1:
Number of Subjects: Approximately 70 subjects (minimum of 38 and up to 120, 
alternative dosing cohorts could potentially add another ~6 to ~40 subjects).
CHANGE 6: Preclinical data on GSK3052230
(new text bold and underlined, deleted text in strikethrough)
PREVIOUS TEXT:
1.4.1.1 Preclinical data on GSK3052230
Seventy-eight tumor-derived xenograft models were treated with GSK3052230 
(FP1039) as a single agent.  Twenty-eight models were found to show significant 
tumor growth inhibition (TGI), including models of NSCLC, small cell lung 
cancer, mesothelioma, squamous cell carcinoma of the head and neck (SCCHN), 
endometrial, colon and breast cancer [Harding, 2010; Harding, 2013].  In lung 
cancer xenografts, GSK3052230-teated tumors harboring FGFR1 gene 
amplification displayed an average of 56% TGI compared to 22% TGI in non-
amplified FGFR1 xenografts (p=0.03)[ Harding, 2013]. FGF2 mRNA levels 
displayed the highest ratio (247.7-fold) of median gene expression between 
GSK3052230 responder and nonresponder xenograft models and was the only 
marker that correlated with response in the subset of non-amplified FGFR1 lung 
cancer xenografts where significant tumor growth inhibition was observed 
[Harding, 2013]. 
To further extend this observation, GSK3052230 was tested in models of 
mesothelioma, a tumor type shown to express high levels of FGF2 mRNA in cell 
lines and in primary tumor specimens [DeYoung, 2014]. GSK3052230 inhibited 
MAPK signaling as evidenced by decreased phospho-ERK levels in both NCI-
H226 and MSTO-211H cells. When both cell lines were grown as tumor 
xenografts in mice, GSK3052230 inhibited tumor growth in a dose-dependent 
manner (NCI-H226: 16 – 78% TGI; MSTO-211H: 20 – 50% TGI). Because FGFs 
also play a key role in angiogenesis, the effects of GSK3052230 on tumor vessel 


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formation in NCI-H226 xenografts were explored [DeYoung, 2014]. Dose-
dependent and statistically-significant reductions in tumor vessel density were 
observed in GSK3052230-treated tumors compared to vehicle-treated tumors 
using MECA-32 endothelial cell IHC staining. Therefore, FGFR1 amplification 
or FGF2 overexpression served as predictive markers of response to 
GSK3052230.
REVISED TEXT:
1.4.1.1 Preclinical data on GSK3052230
Seventy-eight tumor-derived xenograft models were treated with GSK3052230 
(FP1039) as a single agent.  Twenty-eight models were found to show significant 
tumor growth inhibition (TGI), including models of NSCLC, small cell lung 
cancer, mesothelioma, squamous cell carcinoma of the head and neck (SCCHN), 
endometrial, colon and breast cancer [Harding, 2010; Harding, 2013].  In lung 
cancer xenografts, GSK3052230-teated tumors harboring FGFR1 gene 
amplification displayed an average of 56% tumor growth inhibition TGI 
compared to 22% tumor growth inhibition TGI in non-amplified FGFR1 
xenografts (p=0.03)[ Harding, 2013]. FGF2 mRNA levels displayed the highest 
ratio (247.7-fold) of median gene expression between GSK3052230 responder 
and nonresponder xenograft models and was the only marker that correlated with 
response in the subset of non-amplified FGFR1 lung cancer xenografts where 
significant tumor growth inhibition was observed [Harding, 2013]. 
To further extend this observation, GSK3052230 was tested in models of 
mesothelioma, a tumor type shown to express high levels of FGF2 mRNA in 
cell lines and in primary tumor specimens [DeYoung, 2014]. GSK3052230 
inhibited MAPK signaling as evidenced by decreased phospho-ERK levels in 
both NCI-H226 and MSTO-211H cells. When both cell lines were grown as 
tumor xenografts in mice, GSK3052230 inhibited tumor growth in a dose-
dependent manner (NCI-H226: 16 – 78% TGI; MSTO-211H: 20 – 50% 
TGI). Because FGFs also play a key role in angiogenesis, the effects of 
GSK3052230 on tumor vessel formation in NCI-H226 xenografts were 
explored [DeYoung, 2014]. Dose-dependent and statistically-significant 
reductions in tumor vessel density were observed in GSK3052230-treated 
tumors compared to vehicle-treated tumors using MECA-32 endothelial cell 
IHC staining. Therefore, FGFR1 amplification or FGF2 overexpression served 
as predictive markers of response to GSK3052230.
CHANGE 7: Subject selection criteria, Section 3.2
(new text bold and underlined, deleted text in strikethrough)
PREVIOUS TEXT:
Inclusion criteria 2:
Arm C: recurrent after local therapy or unresectable malignant pleaural 
mesothelioma (MPM) with measurable lesions.


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Arm A: Subjects who have received no prior therapy for Stage IV or recurrent 
metastatic disease. Note, to avoid any undue delay of initiating systemic 
chemotherapy for these subjects with newly diagnosed metastatic disease, it is 
allowed to initiate the first cycle of chemotherapy while eligibility for the study is 
still being determined, as long as the first dose of GSK3052230 is given no later than 
Cycle 2 Day 1 of chemotherapy. In addition, subjects with Stage IV disease and 
recurrence after previous NSCLC that has been treated with surgery and adjuvant 
chemotherapy or a radio-chemotherapy regimen with curative intent are eligible, 
provided 6 months has passed since this treatment ended[TNM classification of 
malignant tumors, 7th edition, 2009; Edge, 2010].
Arm B: Subjects who have documented tumor progression (based on radiological 
imaging) or intolerability after receiving only one prior line of platinum containing 
combination chemotherapy for Stage IV or recurrent metastatic disease [TNM 
classification of malignant tumors, 7th edition, 2009; Edge, 2010]. Continued 
‘maintenance’ chemotherapy will be considered part of the first line regimen if the 
same agents are used. If new agents are used for maintenance treatment, this will be 
considered a second line of therapy. Note: first line treatment should not include 
docetaxel but may have included paclitaxel.
Inclusion criteria 3:
Availability of archival tumor tissue required for assessment of deregulated FGF 
pathway signalling, eg, FGFR1 amplification or FGF2 expression. If archival tissue 
is not available, a fresh biopsy is required. Please refer to Section 7.7.1.
In Arms A and B, subjects will be prospectively screened for FGFR1 gene 
amplification using a FISH assay (note, local testing is permitted for pre-screening 
of subjects prior to central testing). For inclusion in this study, based on the central 
laboratory testing, FGFR1 gene amplification must meet one of the following 
criteria: a ratio of FGFR1/CEN 8 of ≥2; or average number of FGFR1 signals per 
tumor nucleus of ≥6; or the percentage of tumor nuclei containing ≥5 FGFR1 signals 
is ≥50%. 
Inclusion criteria 3:
Measurable disease per RECIST version 1.1.
Inclusion criteria 8:
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 for Arm A 
subjects and 0-2 for Arms B and C. 
Inclusion criteria 10, Table 1:
Serum Creatinine
Or
Measured or Calculated Creatinine Clearance c
1.5 x ULN
Or
≥45 mL/min  
Cardiac
Left ventricular ejection fraction
≥LLN (according to local institutional norms) by ECHO


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Exclusion criteria 1:
For Arms A, B, C: Treatment with any FGFR inhibitor.
Exclusion criteria 10:
Symptomatic leptomeningeal or brain metastases or spinal cord compression.
NOTE: Subjects previously treated for these conditions are eligible if they meet both
of the criteria below:
(1) have had stable CNS disease for at least 4 weeks after local therapy as assessed by 
imaging (contrast enhanced magnetic resonance imaging (MRI) or computed 
tomography (CT)),
REVISED TEXT:
Inclusion criteria 2:
Arm C: recurrent after local therapy or unresectable malignant pleural
mesothelioma (MPM) with measurable lesions.
Arm A: Subjects who have received no prior therapy for Stage IIIB or Stage IV or 
recurrent metastatic disease. Note, to avoid any undue delay of initiating systemic 
chemotherapy for these subjects with newly diagnosed metastatic disease, it is 
allowed to initiate the first cycle of chemotherapy while eligibility for the study is 
still being determined, as long as the first dose of GSK3052230 is given no later than 
Cycle 2 Day 1 of chemotherapy. In addition, subjects with Stage IIIB or Stage IV 
disease and recurrence after previous NSCLC that has been treated with surgery and 
adjuvant chemotherapy or a radio-chemotherapy regimen with curative intent are 
eligible, provided 6 months has passed since this treatment ended[TNM 
classification of malignant tumors, 7th edition, 2009; Edge, 2010].
Arm B: Subjects who have documented tumor progression (based on radiological 
imaging) or intolerability after receiving only one or at least one prior line of 
platinum containing combination chemotherapy forStage IIIB or Stage IV or 
recurrent metastatic disease [TNM classification of malignant tumors, 7th edition, 
2009; Edge, 2010]. Continued ‘maintenance’ chemotherapy will be considered part 
of the first line regimen if the same agents are used. If new agents are used for 
maintenance treatment, this will be considered a second line of therapy. Note: first 
line Prior treatment should not include docetaxel but may have included paclitaxel.
Inclusion criteria 3:
Availability of archival tumor tissue required for assessment of deregulated FGF 
pathway signalling, egbut  not limited to, FGFR1 amplification or FGF2 or FGFR1
expression. If archival tissue is not available, a fresh biopsy is required. Please refer 
to Section 7.7.1.
In Arms A and B, subjects will be prospectively screened for FGFR1 gene 
amplification using a FISH assay (note, local testing is permitted for pre-screening 
of subjects prior to central testing) for the dose expansion and the MTD/MFD 
cohorts only. For inclusion in this study, based on the central laboratory testing, 
FGFR1 gene amplification must meet one of the following criteria: a ratio of 


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FGFR1/CEN 8 of ≥2; or average number of FGFR1 signals per tumor nucleus of ≥6; 
or the percentage of tumor nuclei containing  ≥5 FGFR1 signals is ≥50%. 
Inclusion criteria 4:
Measurable disease per RECIST version 1.1 (Arm A and B) and modified 
RECIST for Arm C.
Inclusion criteria 8:
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 for Arms 
A and C subjects and 0-2 for Arms Band C. 
Inclusion criteria 10, Table 1:
Serum Creatinine
Or
Measured or Calculated Creatinine Clearance c
1.5 x ULN
Or
≥45 mL/min (Arm A or B) ≥65 mL/min (Arm C)
Cardiac
Left ventricular ejection fraction
≥50% LLN (according to local institutional norms) by 
ECHO
Exclusion criteria 1:
For Arms A, B, and C: Treatment with any FGFR inhibitor.
Exclusion criteria 10:
Symptomatic leptomeningeal or brain metastases or spinal cord compression.
NOTE: Subjects previously treated for these conditions are eligible if they meet both
of the criteria below:
(1) have had stable CNS disease for at least 4 weeks after local therapy as assessed by 
imaging (contrast enhanced magnetic resonance imaging (MRI) or computed 
tomography (CT)) prior to Day 1,
CHANGE 8: Intra-subject dosing and alternative dosing and schedule cohorts
(new text underlined, deleted text in strikethrough)
NEW TEXT: 
4.2.6
Intra-Subject Dose Escalation or Dose De-escalation
Intra-subject dose escalations may be considered on a case-by-case basis, provided 
that thehigher dose level cohort from the 3+3 phase of the study has been cleared 
without a DLT, and after review of all safety data and approval by a GSK Medical 
Study Physician and discussion with the investigator.  The subject on a lower dose 
level may be increased up to the highest dose level tested.  In this case, the subject 
may begin dosing at the higher dose level as it will have already been demonstrated 
to be tolerable and monitoring will be performed as described in the protocol. For 
example, a subject who enrolled at a dose level below the MTD (or MFD) and may 
be eligible for dose increases if the investigator believes the subject could benefit. 


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4.2.6.1 
Alternative Dosing and Schedule Cohorts
Additional doses and schedules may be explored based on emerging 
pharmacokinetic and safety data. Alterations may be made to the schedule of PK/PD 
sampling sbased on emerging PK  data.  
The sample size of the “alterative dosing and schedule cohorts” will be based on the 
3 + 3 design with potential to expand to up to 30 subjects in this regimen.  
The rationale for exploring this alterative dosing and/or schedule is to expand on the 
safety,  tolerability and preliminary efficacy.
4.5.1.1 Study treatments: Alternative Dosing and Schedule cohorts
Subjects in these expansion cohorts will be dosed based on the pharmacokinetic 
and emerging safety data from the ongoing study. This will be determined at 
FGF117360 Study Investigator meetings (example: dose escalation meeting) and 
the minutes and agreements would be provided to IRB/Ethics prior to dosing in 
this “Alternative Dosing and Schedule” Cohorts.
CHANGE 9: Subject selection criteria, Section 3.2
(new text bold and underlined, deleted text in strikethrough)
PREVIOUS TEXT:
4.7.1
Dose Delays
Chemotherapy be reduced or delayed for toxicity, or in the interest of 
administration in Arm A and Arm B may subject safety per investigator 
discretion.
4.7.4 GSK3052230 Dose Modifications
If the toxicity is potentially related to both GSK3052230 and chemotherapy as 
given inArm A or B, please refer to dose modification for chemotherapy in 
Section 4.7.2 and Section 4.7.3 for potential dose reduction of both study 
treatments.
REVISED TEXT:
4.7.1
Dose Delays
Chemotherapy administration in all arms Arm A and Arm B may be reduced or 
delayed for toxicity, or in the interest of subject safety per investigator discretion.
4.7.4 GSK3052230 Dose Modifications
If the toxicity is potentially related to both GSK3052230 and chemotherapy as 
given inArm A or B, all arms, please refer to dose modification for chemotherapy 


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in Section 4.7.2 and Section 4.7.3 for potential dose reduction of both study 
treatments.
CHANGE 10: Section 7, Time and Events
(new text bold and underlined, deleted text in strikethrough)


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PREVIOUS TEXT:
Table 10
Time and Events Schedule
Time and Events Schedule for FGF117360
Screen
Cycle 1
Cycle 2
Additional Cycles
Every 4 
Cycles, 
D1
EOT
30 
day 
F/U
D1
D8
D9
D15
D1
D8
D15
D1
D8
D15
Visit Window
Tissue prescreen for Arms A and B within 60 days and all other screening assessments within 30 days of C1D1. Visit windows of ±2 days during study 
through EOT, +7 days for F/U. Cycle 1 Day 9 assessments for Arm C only.
Physical exam, weight, 
and height (baseline only)
Not needed C1D1 if screening 
assessments within prior 72 hrs. Complete 
physical exam at screening. Abbreviated 
disease-oriented physical exam 
subsequently.
X
X
X
X
X
X
Ophthalmologic Exam
To be performed by ophthalmologist or 
qualified optometrist.
X
Perform assessment if subject discontinues prior to C4.
C4 only
ECHO
Perform at EOT if subject discontinues 
prior to C4. 
X
C4 only
early 
disc
Forced Vital Capacity
Assess D1 of every odd cycle, Arm C only
X
X
O
Archival Tumor Tissue 
Archived tumor tissue (or fresh biopsy if 
no archival tissue).
X
Brain Scan
X
every 12 weeks 1 week if positive at Screening, or as clinically indicated


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REVISED TEXT:
Table 10
Time and Events Schedule
Time and Events Schedule for FGF117360
Screen
Cycle 1
Cycle 2
Additional Cycles
Every 4 
Cycles, 
D1
EOT
30 
day 
F/U
D1
D8
D9
D15
D1
D8
D15
D1
D8
D15
Visit Window
Tissue prescreen for Arms A and B within 60 days and all other screening assessments within 30 days of C1D1. 
Once the subject provides consent, a tumor sample may be submitted for Arms A and B for FGFR1 amplification at any time (there is no time 
limit or window).  All other screening assessments should be conducted within 30 days of C1D1. Visit windows of ±2 days during study through 
EOT, +7 days for F/U.
Physical exam, weight,
and height (baseline only)
Not needed C1D1 if screening 
assessments within prior 72 hrs. Complete 
physical exam at screening. Abbreviated 
disease-oriented physical exam 
subsequently.
X
X
X
X
X
X
Weight
Note, during dosing period weight 
should be captured on Day 1 of each 
cycle.  It can be obtained more 
frequently per institutional standards 
(example: if required at each infusion)
X
X
X
X
X
X
Ophthalmologic Exam
To be performed by ophthalmologist or 
qualified optometrist. (Visit windows of 
±7 days post baseline).
X
Perform assessment if subject discontinues prior to C4.
C4 only
ECHO
Perform at EOT if subject discontinues 
prior to C4. (Visit windows of ±7 days 
post baseline).
X
C4 only
early 
disc
Forced Vital Capacity
Assess D1 of every odd cycle, Arm C 
only. (Visit windows of ±7 days post 
baseline).
X
X
Odd
Archival Tumor Tissue 
Archived tumor tissue (or fresh biopsy if 
no archival tissue). Once the subject 
provides consent, a tumor sample may 
be submitted for Arms A and B for 
FGFR1 amplification at any time (there 
X


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Time and Events Schedule for FGF117360
Screen
Cycle 1
Cycle 2
Additional Cycles
Every 4 
Cycles, 
D1
EOT
30 
day 
F/U
D1
D8
D9
D15
D1
D8
D15
D1
D8
D15
is no time limit or window).
Brain Scan
Obtain only if symptomatic
X
every 12 weeks 1 week if positive at Screening, or as clinically indicated


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CHANGE 11: Section 7.3.9, Pregnancy Testing and Reporting
(new text bold and underlined, deleted text in strikethrough)
PREVIOUS TEXT:
Any pregnancy that occurs during study participation must be reported using a 
clinical trial pregnancy form.
REVISED TEXT:
Any pregnancy that occurs during study participation (note, study participation 
is defined as the time of the first dose of study drug GSK3052230 is 
administered) must be reported using a clinical trial pregnancy form.
CHANGE 12: Section 7.4.1.5
MOVE TEXT: Move section below from protocol Section 7.4.2.1 to Section 7.4.1.5
Tips on Lymph Node Measurements:
Lymph nodes are considered as a separate organ to measure, and up to two lymph 
nodes can be measured per patient by RECIST v1.1. For unidimensional lymph 
node measurements, use the short axis of the lymph node at baseline and then at 
every followup scan. To be considered as pathologically enlarged and measurable 
at baseline, the lymph node short axis diameter should be ≥15 mm.
CHANGE 13: Section 7.7.1, Central Confirmation of FGF Signalling Pathway Status 
and Translational Research
(new text bold and underlined, deleted text in strikethrough)
PREVIOUS TEXT:
In Arm C, FGF2 and/or FGFR1 expression will be evaluated retrospectively by 
IHC to determine if expression levels of these proteins are associated with 
response to GSK3052230
Any remaining tissue from this study may be used for:

Development and validation of a potential IUO assay and companion 
diagnostic test, e.g., but not limited to FGFR1 gene amplification by FISH or 
FGF2 and/or FGFR1 expression by IHC.

Alternative biomarkers of FGF pathway signalling such as other ligands or 
receptors. 
REVISED TEXT:
In Arm C, FGF2 and/or FGFR1 expression will be evaluated retrospectively by IHC to 
determine if expression levels of FGF2these proteins are associated with response to 
GSK3052230


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Any remaining tissue from this study may be used for:

Development and validation of a potential IUO assay and companion diagnostic test, 
e.g., but not limited to FGFR1 gene amplification by FISH or FGF2 and/or 
FGFR1 expression by IHC.

Alternative biomarkers of FGF pathway signalling such as other ligands or 
receptors. 
CHANGE 14: Section 9.1, 
(new text bold and underlined, deleted text in strikethrough)
PREVIOUS TEXT:
In Arm A and Arm B, the prophylactic use of hematopoietic colony stimulating 
factors is not allowed in Cycle 1.  However, growth factor support therapy (e.g., G-
CSF, GM-CSF) may be administered as a prophylaxis for chemotherapy-related 
neutropenia according to the NCCN Clinical Practice Guidelines in Oncology: 
Myeloid Growth Factors v.1.2010 [NCCN, 2010] or the European Organisation for 
Research and Treatment of Cancer guidelines for the use of G-CSFs [Aapro, 2011]
REVISED TEXT:
In Arm A and Arm B, The prophylactic use of hematopoietic colony stimulating 
factors is not recommended allowed in Cycle 1of the dose escalation portion of 
the study. Local institutional practices vary globally, please discuss with the 
GSK medical team if there is a need to have prophylactic use for subjects 
during the dose escalation period or alternative dose finding period. During 
expansion phase, However, growth factor support therapy (e.g., G-CSF, GM-CSF) 
may be administered as a prophylaxis for chemotherapy-related neutropenia 
according to the NCCN Clinical Practice Guidelines in Oncology: Myeloid Growth 
Factors v.1.2010 [NCCN, 2010] or the European Organisation for Research and 
Treatment of Cancer guidelines for the use of G-CSFs [Aapro, 2011].  
CHANGE 14: Section 12.7, Interim Analysis,
(new text bold and underlined, deleted text in strikethrough)
The rules are also shown in a tabular format below:
REVISED and NEW TEXT:
For Arm C only, the totality of the data will be reviewed prior to stopping for 
futility and the futility stopping rules are non-binding. The final analysis for 
Arm C will require 16/30 responses as specified in Table 16. This is equivalent 
to a binomial test at the final analysis with alpha level 0.10 and power of 82%.
The rules for Parts A, B and C are also shown in a tabular format below:


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CHANGE 15: Section 15.3, Appendix 3: Cockcroft-Gault Formula
(new text bold and underlined, deleted text in strikethrough)
PREVIOUS TEXT:
Example:
Male, actual body weight = 90.0 kg, height = 68 inches
Ideal body weight = 50.0 + (2.3) (68-60) = 68.4 kg.
This subject’s actual body weight is >30% over ideal body weight. Therefore, in this case, the 
subject’s ideal body weight of 68.4 kg should be used in calculating estimated CrCl.
REVISED TEXT:
Example:
Male, actual body weight = 90.0 kg, height = 68 inches
Ideal body weight = 50.0 + (2.3) (68-60) = 68.4 kg.
This subject’s actual body weight is >30% over ideal body weight. Therefore, in this case, the 
subject’s ideal body weight of 68.4 kg should be used in calculating estimated CrCl.


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Amendment 3
Where the Amendment Applies
This amendment applies to all sites.
Summary of Amendment Changes with Rationale
Amendment 3 changed Arm C of the protocol from GSK3052230 monotherapy of 
subjects with solid tumors to combination chemotherapy (GSK3052230 plus pemetrexed 
and cisplatin) of subjects with mesothelioma. Associated additions to the protocol include 
safety precautions for pemetrexed and cisplatin, use of modified RECIST for evaluation 
of clinical response, assessment of forced vital capacity. Patient reported outcomes using 
the Lung Cancer Symptom Scale (LCSS) was added for subjects with lung cancer and 
LCSS-meso for subjects with mesothelioma. Additional background and rationale were 
added. Stopping rules and sample size were modified. Translational research objectives 
were clarified.
List of Specific Changes
Section 1.1 The FGF Pathway in Cancer
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
The last 3 paragraphs of this section have been re-arranged into a new section, Section 
1.2. New text added to the end of the first 3 paragraphs:
FGF ligand-dependent signaling occurs through autocrine production of FGFs
directly from cancer cells or through paracrine production of FGFs from the local 
stroma [Turner, 2010]. FGF2-FGFR1 autocrine feedback loops have been 
characterized in several tumor types and may have a role in drug resistance upon 
exposure to chemotherapy or targeted agents such as gefitinib [Sharpe, 2011; 
Marek, 2009]. Overexpression of FGFs is readily detectable by 
immunohistochemical approaches, as several studies have shown high levels of 
FGF2 protein in MPM tumor specimens [Kumar-Singh, 1999; Davidson, 2004; Li, 
2011]. Further, overexpression or high systemic levels of FGF ligands correlate with 
tumorigenesis and poor patient outcome. These discoveries support the notion that 
specific treatments targeting FGF pathway alterations may provide benefit in this 
population.
Section 1.1 Lung Cancer
This is a new section that was made from the last 3 paragraphs in Section 1.1.
PREVIOUS TEXT:
In animal models, activation of an inducible FGFR1 gene in a mouse mammary tumor 
virus-Wnt-1 transgenic mouse dramatically enhanced mammary tumorigenesis [Pond, 
2010]. Further it has been shown that FGFR1 gene amplification is associated with 


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sensitivity to FGFR1 inhibition in non-small cell lung cancer (NSCLC) cell lines [Dutt, 
2011]. 
Various in vitro studies utilizing NSCLC cell lines reveal that specific FGFs (FGF2 and 
FGF9) as well as FGFR1 and FGFR2 are frequently co-expressed [Berger, 1999; 
Chandler, 1999; Fischer, 2008; Kono, 2009].  In addition, frequent expression of FGF2, 
FGFR1 and FGFR2 mRNA and protein in primary NSCLC specimens have been 
demonstrated [Kono, 2009].
The relevance of the FGF pathway in cancer has also been studied in human primary 
specimens. First, it has been demonstrated that FGFR1 gene is amplified at the genomic 
level in a subset of breast, ovarian, and lung cancer subjects [Knights, 2010]. This 
amplification contributes to the characteristics that allow tumor formation. Further, it has 
been shown that increased expression of FGFRs, FGFR1 gene amplification, or 
production of FGFs correlates with poor prognosis in a variety of tumor types including 
NSCLC [Nguyen, 1994; Kim, 2013]. For example, reduced metastasis-free survival was 
found in a subset of breast cancer subjects carrying the 8p11-12 amplification containing 
the FGFR1 gene [Gelsi-Boyer, 2005; Grose, 2005].  Recently, a focal amplification of the 
FGFR1 gene has been detected in approximately 20% of subjects with squamous NSCLC 
[Weiss, 2010], a histological subtype of NSCLC which previously had very limited 
evidence of molecular alterations amenable to targeted drug therapy. This discovery 
supports the notion that specific treatments targeting FGF pathway alterations may 
provide benefit in this population.
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
In animal models, activation of an inducible FGFR1 gene in a mouse mammary tumor 
virus-Wnt-1 transgenic mouse dramatically enhanced mammary tumorigenesis [Pond, 
2010]. 
Various in vitro studies utilizing NSCLC cell lines reveal that specific FGFs (FGF2 and 
FGF9) as well as FGFR1 and FGFR2 are frequently co-expressed [Berger, 1999; 
Chandler, 1999; Fischer, 2008; Kono, 2009].  In addition, frequent expression of FGF2, 
FGFR1 and FGFR2 mRNA and protein in primary NSCLC specimens have been 
demonstrated [Kono, 2009]. Further it has been shown that FGFR1 gene amplification is 
associated with sensitivity to FGFR1 inhibition in non-small cell lung cancer (NSCLC) 
cell lines [Dutt, 2011].
The relevance of the FGF pathway in cancer has also been studied in human primary 
specimens. First, it has been demonstrated that FGFR1 gene is amplified at the genomic 
level in a subset of breast, ovarian, and lung cancer subjects [Knights, 2010]. This 
amplification contributes to the characteristics that allow tumor formation. Further, it has 
been shown that Increased expression of FGFRs, FGFR1 gene amplification, or 
production of FGFs correlates with poor prognosis in a variety of tumor types including 
NSCLC [Nguyen, 1994; Kim, 2013]. For example, reduced metastasis-free survival was 
found in a subset of breast cancer subjects carrying the 8p11-12 amplification containing 
the FGFR1 gene [Gelsi-Boyer, 2005; Grose, 2005].  Recently, A focal amplification of 
the FGFR1 gene has been detected in approximately 20% of subjects with squamous 
NSCLC [Weiss, 2010], a histological subtype of NSCLC which previously had very 


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limited evidence of molecular alterations amenable to targeted drug therapy. This 
discovery supports the notion that specific treatments targeting FGF pathway alterations 
may provide benefit in this population.
Section 1.3 Mesothelioma
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough) New 
section added:
Malignant mesothelioma remains a deadly disease with few effective therapies. 
Although the incidence of mesothelioma is leveling off in the United States, the 
incidence in Western Europe, China, Russia, and India continues to rise [Ettinger, 
2012]. The median overall survival ranges from 9-17 months regardless of disease 
stage [Tsao, 2009]. The standard of care for the front-line treatment of 
mesothelioma remains cisplatin and pemetrexed with the combination regimen 
having a 41% response rate, a median time to progression of 5.7 months, a median 
overall survival of 12.1 months, and significant improvements in quality of life 
[Vogelzang, 2003; Gralla, 2003]. There remains no widely approved regimen for 
recurrent mesothelioma although pemetrexed (if not used in the front-line), 
vinorelbine, and gemcitabine are agents that have been used with limited success 
[Jassem, 2008; Stebbing, 2009; Manegold, 2005]. A recently completed Phase III 
study of vorinostat versus placebo in 660 patients with recurrent mesothelioma 
reported a median progression-free survival (PFS) of 6.3 versus 6.1 weeks and 
median overall survival (OS) of 31 versus 27 weeks in vorinostat vs. placebo 
respectively, which represents the largest Phase III study completed to date in 
recurrent mesothelioma [Krug, 2011]. These poor PFS and OS data underscore the 
need for more effective therapies in recurrent mesothelioma.
Section 1.4.1.1 Preclinical data on GSK3052230
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough) New 
text added:
Seventy-eight tumor-derived xenograft models were treated with GSK3052230 (FP1039) 
as a single agent.  Twenty-eight models were found to show significant tumor growth 
inhibition, including models of NSCLC, small cell lung cancer, mesothelioma, squamous 
cell carcinoma of the head and neck (SCCHN), endometrial, colon and breast cancer 
[Harding, 2010; Harding, 2013].  In lung cancer xenografts, GSK3052230-teated tumors 
harboring FGFR1 gene amplification displayed an average of 56% tumor growth 
inhibition compared to 22% tumor growth inhibition in non-amplified FGFR1 xenografts 
(p=0.03)[ Harding, 2013]. FGF2 mRNA levels displayed the highest ratio (247.7-fold) 
of median gene expression between GSK3052230 responder and nonresponder 
xenograft models and was the only marker that correlated with response in the 
subset of non-amplified FGFR1 lung cancer xenografts where significant tumor 
growth inhibition was observed [Harding, 2013]. Therefore, FGFR1 amplification 
or FGF2 overexpression served as predictive markers of response to GSK3052230.


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Section 1.5.3 Pemetrexed/cisplatin
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough) New 
section added:
Pemetrexed is a folate analog inhibitor that disrupts folate-dependent metabolic 
processes essential for cell replication. In vitro studies have shown that pemetrexed 
inhibits thymidylate synthase, dihydrofolate reductase, and glycinamide 
ribonucleotide formyltransferase, which are folate-dependent enzymes involved in 
de novo biosynthesis of thymidine and purine nucleotides. Cisplatin is a heavy-metal 
complex containing a central platinum atom with 2 chloride atoms and 2 ammonia 
molecules in the cis position. Pemtrexed in combination with cisplatin is 
recommended for the treatment of mesothelioma [Alimta PI, 2004].
The most common adverse reactions (incidence ≥20%) with single-agent use of 
pemetrexed are fatigue, nausea, and anorexia. Additional common adverse reactions 
when used in combination with cisplatin include vomiting, neutropenia, leukopenia, 
anemia, stomatitis/pharyngitis, thrombocytopenia, and constipation [Alimta PI, 
2004].
Common adverse reactions (incidence ≥20%) associated with cisplatin include 
nephrotoxicity, ototoxicity, myelosuppression, and nausea/vomiting. Other toxicities 
include vascular complications, serum electrolyte imbalance, Hyperuricemia, 
neurotoxicity, ocular toxicity, anaphylactic-type reactions, and hepatotoxicity 
[Platinol PI, 2010].
Section 1.6 Summary of Risk Management
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough) New 
text added:
Anterior uveitis:
•
Optic neuritis, papilledema, and cerebral blindness have been reported in 
patients receiving standard recommended doses of cisplatin.
Peripheral neuropathy:
•
Peripheral neuropathy is a potentially overlapping toxicity between GSK3052230 
and, taxanes such as paclitaxel and docetaxel, and cisplatin.
Hematologic toxicity:
Furthermore, paclitaxel or, docetaxel, and cisplatin have known bone-marrow toxicity


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Nephrotoxicity:
•
Dose-related and cumulative renal insufficiency, including acute renal 
failure, is the major dose-limiting toxicity of cisplatin. Renal toxicity has been noted 
in 28% to 36% of patients treated with a single dose of 50 mg/m2. It is first noted 
during the second week after a dose and is manifested by elevations in BUN and 
creatinine, serum uric acid and/or a decrease in creatinine clearance. Renal toxicity 
becomes more prolonged and severe with repeated courses of the drug. Renal 
function must return to normal before another dose of cisplatin can be given.
•
One patient with severe renal impairment (creatinine clearance 19 mL/min) 
who did not receive folic acid and vitamin B12 died of drug-related toxicity 
following administration of pemetrexed alone.
Ototoxicity:
•
Ototoxicity has been observed in up to 31% of patients treated with a single 
dose of cisplatin 50 mg/m2, and is manifested by tinnitus and/or hearing loss in the 
high frequency range (4000 to 8000 Hz). Decreased ability to hear normal 
conversational tones may occur. Deafness after the initial dose of cisplatin has been 
reported. Hearing loss can be unilateral or bilateral and tends to become more 
frequent and severe with repeated doses. Careful monitoring per standard of care 
should be performed.
Section 2 Objectives and Endpoints and Synopsis
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
Primary Objectives:
To characterize the safety and tolerability of GSK3052230 in combination with 
chemotherapy regimens (Arm A and B) or as single agent (Arm C).
To determine the regimen of GSK3052230 in combination with chemotherapy (Arm A 
and B) for evaluation in future studies based on the maximum tolerated dose (or 
maximum feasible dose).
Primary Endpoints:
Best response defined as complete or partial response, stable disease or progressive 
disease according to RECIST 1.1 or modified RECIST (for MPM)
ORR defined as the proportion of subjects with investigator-assessed confirmed complete 
response or partial response per RECIST 1.1 or modified RECIST (for MPM)
Secondary Objectives
Assess improvement in Pulmonary Function Tests in Patients with MPM.


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Secondary Endpoints
PFS is defined as the interval between first dose of GSK3052230 and the earliest date of 
disease progression or death due to any cause by investigator assessment per RECIST 1.1 
or modified RECIST (for MPM)
Change from baseline in Forced Vital Capacity (FVC) in patients with MPM.
Exploratory Objectives
To identify biomarkers that may predict response or resistance
To evaluate the pharmacodynamic response in tumors circulation following treatment 
(re-biopsy is required for tumors that are accessible for biopsy) for Arm C
To investigate additional measures of FGF signaling pathway deregulation as potential 
predicative biomarkers for GSK3052230 in tissue.
To evaluate changes in patient reported outcomes.
Exploratory Endpoints
Changes in proteins/RNA circulating biomarkers (eg, proteins) implicated in FGFR or 
disease biology signaling (eg. MAPK/PI3K pathways) and/or cancer development
signalling in pre- and post -dose tumor tissue blood samples.
Association of FGFR1 gene amplification with clinical response to support the 
development of a laboratory developed test for an investigation use (LDT/only test (IUO) 
and potential companion diagnostic for subject selection.
Identification and validation of alternative measures of FGF signaling pathway 
deregulation as retrospectively (eg, FGF2 overexpression) as predictive biomarkers for 
subject selection and potential development of a companion diagnostic
Change from baseline and association with ORR in observer and patient assessed 
components of the Lung Cancer Symptom Scale (LCSS) and LCSS-mesothelioma
Section 3.1 Number of Subjects
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
Approximately 70 subjects will be enrolled in the study (minimum of ~3638 and up to 
~104 approximately 120). In addition to minimum and maximum sample sizes for each 
arm, sample sizes that would be expected under the null and alternative hypothesis rates 
for Arms A and B are provided in Section 12.3.


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Section 3.2.1 Inclusion Criteria and Synopsis
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
Inclusion criterion 2:
Arm C: advanced solid tumor with deregulated FGF pathway signaling, for which all 
lines of standard therapies have been exhausted or for which no standard treatment is 
available.
Arm C: recurrent after local therapy or unresectable MPM with measurable lesions
Arm C: Subjects who have exhausted all lines of standard therapies or for whom there is 
no standard treatment for the specific tumor.  Note: squamous NSCLC subjects who have 
documented tumor progression (based on radiological imaging) after receiving two or 
more prior lines of systemic therapy (including platinum containing chemotherapy 
regimens) for Stage IV or recurrent metastatic disease may be enrolled [ of malignant 
tumors, 7th edition, 2009; , 2010].  Subjects with ER positive breast cancer having 
disease progression while on aromatase inhibitor therapy are allowed to continue 
aromatase inhibitor therapy, subjects with prostate cancer may continue to be treated with 
GnRH as clinically appropriate, and subjects with carcinoid cancer may continue 
treatment with octreotide.
Arm C: Subjects who have received no prior systemic therapy for MPM.
Inclusion criterion 3:
3.
Availability of archival tumor tissue required for assessment of deregulated FGF 
pathway signaling e.g.eg, FGFR1 amplification or FGF2 expression.
In Arm C, FGF2 expression by IHC will be evaluated retrospectively in tissue 
samples by a central laboratory and is not required for study entry.
Inclusion criterion 7:
For Arm A and B: 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 
10.1.2 for at least 2 weeks prior to administration of the first dose of study treatment and 
for at least 6 months after the last dose of chemotherapy, to allow for clearance of any 
altered sperm. Arm C: No male contraception restrictions.
Section 3.2.2 Exclusion Criteria and Synopsis
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
Exclusion Criterion 1:
For Arms B, C: Treatment with any anti-cancer therapy (for biological anti-cancer 
therapies see criteria 2.) during the preceding 4 weeks or within 4 half-lives of the 


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therapy, whichever is longer (except: anti-cancer hormonal treatment of prostate cancer, 
breast cancer or octreotide for treatment of carcinoid cancer).
Exclusion criterion 11:
Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs 
chemically related to study drugs (GSK3052230, docetaxel, paclitaxel, carboplatin, 
pemetrexed, cisplatin) and or their excipients that contraindicates their participation
Section 4.1 Discussion of Study Design and Synopsis
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
This will be a multi-arm, multicenter, non-randomized, parallel-group, uncontrolled, 
open-label Phase IB study designed to evaluate the safety, tolerability and preliminary 
activity of GSK3052230 in combination with paclitaxel + carboplatin (Arm A), in
combination with docetaxel (Arm B), or GSK3052230 as monotherapy in combination 
with pemetrexed + cisplatin (Arm C). All subjects enrolled will have documented 
deregulation of FGF pathway signaling (e.g. FGFR gene amplification).
Previous Figure 1, Study Schema:


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Revised Figure 1, Study Schema:
Pemetrexed/Cisplatin +
GSK3052230
3+3 design to determine
MTD  (MFD) in subjects with MPM
Arm C
Paclitaxel/Carboplatin +
GSK3052230
N=at least 12 and up to 30 sqNSCLC
Docetaxel+ GSK3052230
3+3 design to determine MTD (MFD) 
in subjects with sqNSCLC
Docetaxel + GSK3052230
N=at least 14 and up to 30 sqNSCLC
Arm B
Paclitaxel/Carboplatin +
GSK3052230
3+3 design to determine
MTD  (MFD) in subjects with sqNSCLC
Arm A
Pemetrexed/Cisplatin +
GSK3052230
N=at least 12 and up to 30 MPM
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
Enrollment to Arms A and B will open first and simultaneously. Dose escalation in Arm 
A and Arm B will follow a 3+3 design as outlined in Section 4.2 for determination of 
MTD (or MFD).  A cohort expansion of at least 12 subjects will be treated at the MTD 
(or MFD) in each arm, with the option of expanding to a maximum of 30 subjects. 
Stopping rules based on anti-tumor activity are outlined in Section  and Section were
derived according to a predictive probability design for each arm of the study and are 
detailed in Section 4.2.1, Section 4.2.2 that allows for evaluation of success, and 4.2.3
futility after each patient rather than at only two stages as in traditional designs.  The 
decision on the timing of the initiation of Arm C will be determined by GSK and will be 
communicated to investigative centers directly and expediently in the form of a letter. At 
least 12 subjects and up to a maximum of 20 subjects will be treated in Arm C.
GSK3052230 will be administered as a 30-minute intravenous (i.v.) infusion once a week 
(Day 1, Day 8, Day 15) of each 21-day cycle. Paclitaxel/carboplatin and, docetaxel, and 
pemetrexed/cisplatin will be administered i.v. on Day 1 of each 21-day cycle. The 
number of cycles of paclitaxel/carboplatin will be limited to 4 to 6 cycles. Subjects may 
continue to receive docetaxel and pemetrexed/cisplatin until disease progression or as 
long as they are considered to derive benefit from treatment.  Subjects who discontinue 
chemotherapy (Arm A and Arm B) for reasons other than disease progression, may 
continue to receive GSK3052230 as long as they are considered to derive benefit from 
the treatment according to the criteria in Section 6.3. After discontinuation of 
GSK3052230, subjects will return after approximately 30 days (see Time and Events 
Table Section 7.1) for a follow-up visit to collect safety assessments, after which they 
will be considered to have completed the study.
Blood samples for pharmacokinetic, pharmacogenetic, and translational research will be 
obtained at specified times during the study.  Efficacy will be assessed every 2 cycles 
during the first year and every 4 cycles thereafter.  Paired tumor biopsies pre-dose and 
post-dose will be required from a minimum of 6 subjects with accessible tumors for 


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repeated biopsy in Arm C.  Additional subjects may be asked to provide biopsies based 
on emerging data.
Section 4.2 GSK3052230 plus Chemotherapy in Arm A and Arm B
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
Arm A and Arm B Dose escalation will follow a 3 + 3 dose-escalation procedure . . .
Section 4.2.1 Arm A
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
A total of at least 12 subjects will be enrolled at the target dose to further evaluate safety 
and efficacy. After 12 subjects have been enrolled, the number of observed confirmed 
responses will guide further enrolment according to the stopping rules.  The futility 
boundaries (inclusive) for ORR for Arm A are 0/12, 1/14, 2/17, 3/20, 4/22, 5/24, 6/26, 
7/27, 8/28, 9/29, and 10/30 subjects and are shown in tabular format in Section 12.7
rules summarized in Section .. Up to 30 subjects will be enrolled in Arm A. All available 
data will be considered in making enrollment decisions
Section 4.2.2 Arm B
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
A total of at least 1214 subjects will be enrolled at the target dose to further evaluate 
safety and efficacy. After 1214 subjects have been enrolled, the number of observed 
confirmed responses will guide further enrolment according to the stopping rules 
summarized. The futility boundaries (inclusive) for ORR for Arm B are 0/14, 1/22, 
2/26, 3/28, 4/29, and 5/30 subjects and are shown in tabular format in Section 12.7.. 
Up to 30 subjects will be enrolled in Arm B. All available data will be considered in 
making enrollment decisions.
Section 4.2.3 Arm C (new section)
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
Arm C will open for enrollment subsequent to Amendment 3. The starting dose of 
GSK3052230 (Dose Level 0) in Arm C will be 10 mg/kg as long as the 5 mg/kg dose 
in combination with chemotherapy in Arm A did not exceed the MTD. Otherwise 
the starting dose level in Arm C will be Dose Level -1. Dose levels and escalation/de-
escalation schema for GSK3052230 in combination with pemetrexed and cisplatin is 
presented in Table 3.  Depending on emerging data, additional intermediate or 
lower dose-levels beyond those described may be explored.


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Table 5
Combination Therapy: Arm C GSK3052230 + Pemetrexed + 
Cisplatin
Dose Level
Dose of GSK3052230
(Weekly)
Pemetrexed + Cisplatin
(once every 21 days)
Dose Level -2
5 mg/kg
400 mg/m2 + 60 mg/m2
Dose Level -1
5 mg/kg
500 mg/m2 + 75 mg/m2
Starting Dose Level 0
10 mg/kg
500 mg/m2 + 75 mg/m2
Dose Level 1
20 mg/kg
500 mg/m2 + 75 mg/m2
A total of at least 12 subjects will be enrolled at the target dose to further evaluate
safety and efficacy. After 12 subjects have been enrolled, the number of observed 
confirmed responses will guide further enrolment according to the stopping rules. 
The futility boundaries (inclusive) for ORR for Arm C are 2/12, 3/14, 4/16, 5/18, 
6/20, 7/21, 8/23, 9/24, 10/25, 11/26, 12/27, 13/28, 14/29 and 15/30 subjects and are 
shown in tabular format in Section 12.7. Up to 30 subjects will be enrolled in Arm 
C. All available data will be considered in making enrollment decisions.
Section 4.3 GSK3052230 in Arm C
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
Section 4.3 GSK3052230 in Arm C
At least 6 and up to 18-20 subjects will be treated in Arm C at a dose of 20 mg/kg. Other 
doses may be explored in this arm
Section 4.3.1 Rationale for Evaluation of GSK3052230 in Chemotherapy 
Combinations
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
4.3.1
Rationale for Evaluation of GSK3052230 in Chemotherapy Combination 
(Paclitaxel + Carboplatin, or Docetaxel) in NSCLC with deregulated FGF pathway 
signalingCombinations
FGFR1 amplification has been identified in approximately 20% of squamous NSCLC 
with suggested tumor dependence on FGF pathway signaling [, 2010].  FGFR1 
amplification has been associated with significantly shorter disease free and overall 
survival in NSCLC [Kim, 2013; Heist, 2012].  Carboplatin and paclitaxel can be used in 
first line therapy of NSCLC and docetaxel is a standard second line agent.  Pemetrexed 
and cisplatin is the standard first line therapy for mesothelioma. Additive antitumor 
effect was demonstrated in tumor xenograft models treated with the combinations of 
GSK 3052230 and chemotherapy including paclitaxel and carboplatin as well as 
docetaxel. Malignant pleural mesothelioma (MPM) is a tumor type where FGF2 
ligand overexpression has been observed in a high percentage of primary specimens 
and where GSK3052230 preclinical efficacy has been observed in xenograft models. 
Based on the clinical and preclinical data, the combination of GSK3052230 in 


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combination with chemotherapy will be investigated in patients with NSCLC or with 
mesothelioma.
Section 4.3.2 Rationale for Evaluation of GSK3052230 Monotherapy
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
Section 4.3.2 Rationale for Evaluation of GSK3052230 Monotherapy
It is anticipated that GSK3052230 monotherapy will only demonstrate anti-tumor activity 
in the presence of deregulated FGF signaling pathway, specifically amplification or 
overexpression of FGF ligand(s) and/or receptor(s).  Arm C will enroll subjects with 
deregulated FGF pathway signaling (e.g. FGFR gene amplification, FGF ligand 
overexpression, etc.).  These subjects should have failed available standard therapies or 
have a cancer for which no standard therapies exists
Section 4.3.3 Rationale for Endpoints
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
Symptom assessments as measured by the LCSS and LCSS-meso were added to 
increase the understanding of the patient experience and perceptions.
Section 4.5.4 Pemetrexed and Cisplatin
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
Section 4.5.4 Pemetrexed and Cisplatin
Subjects in Arm C will receive pre-treatment for pemetrexed and cisplatin 
according to institutional standards. Pemetrexed according to the dose level being 
investigated (Table 5) will be administered intravenously over 10 minutes (or 
according to local clinical standards) on Day 1 of each 21 day treatment cycle 
followed 30 minutes later by i.v. cisplatin infused over 2 hours.
Subjects will be hydrated and pre-medicated with folic acid and vitamin B12 
supplements in order to reduce the incidence and severity of hematologic and 
gastrointestinal toxicities as well as cutaneous hypersensitivity reactions as per 
institutional guidelines.  Recommendations for pre-medication are as follows:
•
1-2 liters of fluid infused for 8-12 hours prior to cisplatin dose
•
350-1000 g folic acid, once daily, by mouth for seven days preceding the 
first dose of pemetrexed, during treatment, and for 21 days following the last dose of 
pemetrexed
•
1000 g vitamin B12 by intramuscular injection in the week preceding the 
first dose of pemetrexed and every three cycles thereafter (subsequent vitamin B12 
injections may be given on the same day as pemetrexed)


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•
4 mg dexamethasone (or equivalent), twice daily, by mouth the day before, 
the day of, and the day after pemetrexed administration   
Additional information can be found in the prescribing information for pemetrexed 
[Alimta Package Insert, 2012] and cisplatin [Platinol, 2010].
Section 4.7.2 Hematologic Toxicity Related to Chemotherapy
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough) Added 
to last row of Modification Instructions, Table 7
Arm C: Restart combination chemotherapy reduced by 1 level for the 
chemotherapy dose according to Table 5.
Section 4.7.3 Non-hematologic Toxicity Related to Chemotherapy
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
Table 8 Chemotherapy Dose Delay and Modifications for Non-hematologic Toxicity
Adverse Event
Action
Non-hematological, drug-related 
Grade 3 or 4 (except alopecia)
Hold chemotherapy until recovery to Grade ≤1.
Arm A: Restart at dose levels reduced by 1 level for both agents 
according to Table 3.
Arm B: Restart docetaxel reduced by 1 level according to Table 4
Arm C: Restart combination chemotherapy reduced by 1 level 
for the chemotherapy dose according to Table 5
Exceptions
Grade 2 neurotoxicity
Arm C: Withhold study treatment until recovery to Grade 1; 
then resume treatment with cisplatin reduced by 50% of 
previous dose
Grade 3 or 4 Peripheral neuropathy
Neurotoxicity
Withhold study treatment until patient recovers recovery to Grade 
1; then resume treatment at dose reduced by 2 levels according to 
Table 3 (Arm A) or Table 4 (Arm B). Permanently discontinue 
chemotherapy in Arm C. If treatment delay is more than 2 weeks, 
re-initiation of treatment should be agreed with the GSK study 
physician.
Mucositis, Grade 3 or 4
Arm C: Reduce pemetrexed only by 50% of previous dose
Serum creatinine <1.5 mg/100mL 
or BUN <25mg/100mL
Arm C: Hold chemotherapy until serum creatinine >1.5 
mg/100mL or BUN >25mg/100mL
Creatinine clearance <45 mL/min
Arm C: Hold chemotherapy until creatinine clearance ≥45 
mL/min


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Section 5.1.2 Chemotherapeutic Agents
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
Section 5.1.2 Paclitaxel + Carboplatin and Docetaxel Chemotherapeutic Agents
Paclitaxel, carboplatin, and docetaxel, pemetrexed, and cisplatin will be sourced locally 
from commercial stock, except in countries where Regulatory Authorities mandate that 
the Sponsor must supply all non-investigational product (IPs) required for study 
participation. Investigators are responsible for ensuring that subjects receive supplies of 
paclitaxel, carboplatin, and docetaxel, pemetrexed, and cisplatin for the entire duration 
of the study, as appropriate.  The contents of the label will be in accordance with all 
applicable regulatory requirements.
Section 5.2 Preparation/Handling/Storage of GSK3052230
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
Refer to the SPM (the FGF117360 Pharmacy Manual) for storage conditions.
Section 6.1 Screen Failures
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
Section 6.1 Screen and Baseline Failures
Data for screen and baseline failures....


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Section 7.1 Time and Event Schedules
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
Table 10. Time and Events Schedule for FGF117360
Screen
Cycle 1
Cycle 2
Additional Cycles
Every 4 
Cycles, 
D1
EOT
30 
day 
F/U
D1
D8
D9
D15
D1
D8
D15
D1
D8
D15
Vital Signs
Arms A + B: Within 20 min before 
start of first chemotherapy infusion 
and within 20 min before start of 
GSK3052230 infusion.
Arm C: Before start of 
GSK3052230 infusion.
X
X
X
X
Forced Vital Capacity
Assess D1 of every odd cycle
X
X
O
Tumor Tissue (fresh biopsy) for 
biomarker research
Arm C only: (minimum of 6 
subjects). Predose sample +7 
days prior to C1D1. EOT sample 
only upon progression.
X
X
X
Circulating Biomarkers 
Plasma sample collected predose 
(+7 days prior to C1D1)
X
X
X
Arm C: D1 every cycle 1 
year, then D1 every 2 
cycles
X
LCSS (Arms A and B); LCSS-
meso (Arm C)
Must be administered first 
before any other tests or 
procedures. Study staff should 
check for completeness.
X
X
X
X
X
X
ARMS A, B, C: GSK3052230
30 minute infusion. 
X
X
X
X
X
X
X
X
X
ARM B: Docetaxel 
GSK3052230 infused & 
observed 1 hr prior to 
docetaxel chemotherapy
infusions.
X
X
X
ARM C: Pemetrexed + Cisplatin 
GSK3052230 infused & 
observed 1 hr prior to 
chemotherapy infusions.
X
X
X


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Table 10. Time and Events Schedule for FGF117360
Screen
Cycle 1
Cycle 2
Additional Cycles
Every 4 
Cycles, 
D1
EOT
30 
day 
F/U
D1
D8
D9
D15
D1
D8
D15
D1
D8
D15
Table 11. FGF117360 Pharmacokinetic Sampling Schedule
Limited PK
Extensive PK
Extensive PK
Limited PK
Extensive PK
Time 
When
Window
Arm A or Arm B
Arm A
Arm B
Arm C
Arm C
n=20pts in Arm A 
n=20pts in Arm B
each arm
n>=10pts
n>=10pts
Remaining 
patients
n>= 6 10pts
Cycle 1 Day 1
Prior to infusion of 
GSK3052230
Up to 12 hr prior to infusion of 
GSK3052230
GSK3052230 PK
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 PK
End of infusion of 
GSK3052230
Up to 5 min prior to end of 
infusion of GSK3052230
GSK3052230 PK
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 PK
1hr after end of infusion of 
GSK3052230
10 min but after ECG
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 PK
2hr after end of infusion of 
GSK3052230 or end of 
docetaxel infusion
10 min or up to 5 min prior to 
end of docetaxel infusion
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 PK
Cycle 1 Day 8
Prior to infusion of 
GSK3052230
Up to 12 hr prior to infusion of 
GSK3052230
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 PK
Cycle 1 Day 9
(time relationship to tumor 
biopsy not infusion time)
within 1 hr of tumor biopsy
GSK3052230 
PK
GSK3052230 PK
Cycle 2 Day 1
Prior to infusion of 
GSK3052230
Up to 12 hr prior to infusion of 
GSK3052230
GSK3052230 PK
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 PK
End of infusion of 
GSK3052230
Up to 5 min prior to end of 
infusion of GSK3052230
GSK3052230 PK
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 PK
1 hr after start of 
paclitaxel infusion or end 
of docetaxel or 
pemetrexed infusion
10 min for paclitaxel or up to 
5 min prior to end of docetaxel 
infusion or up to 1 min prior 
to end of pemetrexed 
infusion
GSK3052230 
PK
Paclitaxel PK
GSK3052230 
PK
Docetaxel PK
GSK3052230 PK
Pemetrexed PK
1 hr after end of 
pemetrexed infusion
20 min
Pemetrexed PK
up to 5 min prior to end of 
Paclitaxel PK
Docetaxel PK
Pemetrexed PK


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Table 10. Time and Events Schedule for FGF117360
Screen
Cycle 1
Cycle 2
Additional Cycles
Every 4 
Cycles, 
D1
EOT
30 
day 
F/U
D1
D8
D9
D15
D1
D8
D15
D1
D8
D15
End of paclitaxel infusion 
or 2 hr after end of 
docetaxel or pemetrexed
infusion
paclitaxel infusion or 20 min 
for docetaxel and 
pemetrexed
2 hr after end of paclitaxel 
infusion or 5 hr after end 
of docetaxel or 
pemetrexed infusion
30 min
(selected sites)
GSK3052230 
PK
Paclitaxel PK
(selected sites)
GSK3052230 
PK
Docetaxel PK
(selected sites)
GSK3052230 PK
Pemetrexed PK
Cycle 4 Day 1
Cycle 6 Day 1
Cycle 12 Day 1
Prior to infusion of 
GSK3052230
Up to 12 hr prior to infusion of 
GSK3052230
GSK3052230 PK
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 PK
Cycle 4 Day 1
End of infusion of 
GSK3052230
Up to 5 min prior to end of 
infusion of GSK3052230
GSK3052230 PK
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 PK
Cycle 6 Day 1
Cycle 12 Day 1
EOT
GSK3052230 PK
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 PK
30 days FU
At time of immunogenicity 
sample
GSK3052230 PK
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 
PK
GSK3052230 PK


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Section 7.2 7.2.
Demographic/Medical History and Baseline Assessments
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
•
LCSS for Arms A & B
•
For Arm C only LCSS (meso) and forced vital capacity
Section 7.2.1 Critical Baseline Assessments
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
. . .For Arm C, deregulation of FGF pathway signaling pathway may be assessed locally 
or centrally (additional details will be in SPM). 
For Arm C, forced vital capacity will be assessed at screening.
Section 7.3.4 Forced Vital Capacity
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
7.3.4. Forced Vital Capacity
Forced vital capacity will be measured in Arm C at each scheduled disease 
assessment using standard methods (Refer to the SPM for details).
Section 7.3.8 Laboratory Assessments
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
Table 12
List of Clinical Laboratory Tests
Blood urea nitrogen (BUN), Creatinine, Uric Acid, creatinine clearance
Section 7.4 Evaluation of Anti-cancer Activity
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
CT:  (second paragraph) For Arms A and B, RECIST 1.1 analysis. . . .
For Arm C, modified RECIST will be used. Tumor thickness perpendicular to the 
chest wall or mediastinum will be measured in two positions at three separate levels 
on thoracic CT scans. The sum of the six measurements defines a pleural 
unidimensional measure. Bidimensionally measureable lesions will be measured 
unidimensionally as for RECIST 1.1. All measurements were added to obtain the 
total tumor measurement. The Image Acquisition Guidelines portion of the SPM
should be consulted for additional details on imaging protocols.


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Brain Scan: In subjects with known brain metastases (criteria outlined in Section 3.2), a 
contrast-enhanced MRI (preferred) or CT of the brain must be obtained within 3530 days 
prior to receiving the first dose of the study medication
Section 7.4.1 Evaluation of Response in Arm A and Arm B (RECIST 1.1)
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
Section 7.4.1 Evaluation of Response Criteria in Arm A and Arm B (RECIST 1.1)
Section Evaluation of Response in Arm C: Mesothelioma
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
7.4.2. Evaluation of Response in Arm C: Mesothelioma
7.4.2.1.
Mesothelioma Tumor Imaging
Clinical trials of therapeutic agents in MPM may be compromised by inaccuracy of 
tumor measurements due to the unique pattern of growth of mesothelioma [Byrne, 
2004; Tsao, 2011]. Malignant mesothelioma commonly grows as a rind and thus 
may not produce spherical lesions with bidimensional, measurable diameters 
[Byrne, 2004]. Modification of RECIST criteria have been recommended to address 
the difficulties in measurement of lesions [Byrne, 2004; Tsao, 2011]. In subjects with 
mesothelioma, it is requested that disease assessments using both RECIST v1.1 
criteria AND modified RECIST criteria be performed.
Uni-dimensional measurements of tumor thickness perpendicular to the chest wall 
or mediastinum should be performed, measured in 2 sites at 3 different levels on the 
CT scan. Transverse cuts used for measurement must be at least 1 cm apart, and 
related to anatomical landmarks in the thorax, preferably above the level of division 
of the main bronchi. At reassessment, pleural thickness must be measured at the 
same position and level. Nodal, subcutaneous, and other bidimensionally 
measurable lesions are measured unidimensionally as per the RECIST v1.1 criteria. 
Unidimensional measurements are added to produce the total tumor measurements 
(e.g., the sum of 6 pleural thickness measurements = one univariate diameter).
Overall tips for measurement of mesothelioma by modified RECIST [Tsao, 2011]:
1.
Larger lesions are easier and more accurate to measure. Choose the larger or 
thickest of the pleural disease to measure. Magnifying the image may make an 
easier measurement.
2.
The short-axis diameter is defined as the shortest pathway from the tip of the 
tumor to the chest wall.
3.
Ensure that that differentiation of normal chest wall from tumor is easy at 
the point of measurement


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4.
To ensure accuracy, all measurements must be performed electronically in 
the same window setting on consecutive studies. It is recommended that the “soft 
tissue” setting (not lung windows) be used, as it enables accurate pleural mass 
measurements with the electronic calipers and avoids the incorporation of chest wall 
or mediastinal fat within the calculations.
5.
CT scan slices up to 5 mm can be used, but for greater accuracy, thinner 
slices such as 2.5 mm are preferable. Ideally, all subsequent CT scans should use the 
same slice thickness.
6.
To limit interobserver variability, in measuring tumor response, it is 
preferred that the same clinician measure the tumors at baseline and on all 
subsequent CT scans.
7.
The pleural disease to be measured should have a short-axis diameter of at 
least 1 cm, as lesions less than 1 cm are considered nonmeasurable.
8.
To obtain the short axis of the disease, with electronic calipers, measure the 
distance between the point where the tumor abuts the chest or the mediastinal 
border and the point where the pleural disease touches the lung. The shortest route 
possible is the one perpendicular to the chest wall/mediastinum.
9.
Avoid measuring regions where the tumor infiltration obscures the interface 
of tumor to normal tissue. A good interface for measurement usually is one where 
the tumor abuts fat or an intact rib/vertebral body, as the density of the pleural 
tumor differs significantly from bone or fat and the difference can be easily 
observed. Avoid choosing an interface of tumor with muscle, as muscle and tumor 
have similar CT densities and are often difficult to distinguish when they abut one 
another.
10.
Following the instructions in #5, choose three different axial slices, preferably 
above the level of the main bronchi and record two measurements per slice, thus 
resulting in six separate measurements.
11.
If any nodal, subcutaneous or other bidimensionally measurable lesions are 
available, they should undergo unidimensional measurements by RECIST v1.1 and 
be added to the total obtained in #7 above.
Tips on Lymph Node Measurements:
Lymph nodes are considered as a separate organ to measure, and up to two lymph 
nodes can be measured per patient by RECIST v1.1. For unidimensional lymph 
node measurements, use the short axis of the lymph node at baseline and then at 
every followup scan. To be considered as pathologically enlarged and measurable at 
baseline, the lymph node short axis diameter should be ≥15 mm.


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7.4.2.2.
Prior Scan collection
Collection of up to three prior tumor imaging scans performed prior to baseline 
scans at study entry will also be encouraged in subjects whose scans are available 
for review. These scans may be collected and sent to an independent radiologist for 
review. The slope of tumor growth prior to study entry and following treatment may 
be compared in subsequent analyses. Such comparisons may be important in 
evaluation of the clinical significance of subjects achieving a clinical response, 
particularly in those subjects achieving SD.
Section 7.4.3 Patient Reported Outcomes
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
7.4.3. Patient Reported Outcomes
The Lung Cancer Symptom Scale or the Lung Cancer Symptom Scale-
mesothelioma [LCSS (-meso)] will be self-administered by subjects (patient scales) 
and completed by the investigator (observer scales) as indicated in the Time and 
Events schedule (Table 10). The LCSS(-meso) consists of nine (meso: eight) patient-
reported items (visual analogue scale with a range from 0 to100) and six observer 
reported items and is validated in lung cancer and in mesothelioma patients [Hollen, 
2006]. Using visual analogue scales, the patient scale measures the intensity of 
patient responses for appetite, fatigue, cough, dyspnea, hemoptysis, pain, and 
summary items symptoms of lung cancer, activity level and quality of life. An 
example questionnaire can be found in the SPM. The LCSS-meso was chosen 
because of its focus on disease-related symptoms, the possibility to combine the 
patient’s perception with the investigator’s contextual knowledge, its demonstrated 
concept and content validity, ease of application and minimal burden to patients. 
It is important that the LCSS patient scale is administered at the start of the clinic 
visit before any other study assessments are performed.
Section 7.5.2 Pharmacokinetic Sample Analysis
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
Concentrations of GSK3052230 and selected chemotherapy will be determined…
Section 7.7 Translational Research
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
7.7.1. Tumor Biomarker Analysis
7.7.1.1.
Fresh Pre-and Post-dose Tumor Tissues
Pre and post dose tissues, as well as tissues collected at progression will be analyzed for 
the appropriate protein and/or RNA biomarkers of FGFR pathway and 
proliferation/apoptosis (e.g. Ki67, CC3, etc).  Collected tissues may also be used to 


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analyze the protein and DNA markers of RTK/MAPK/PI3K pathway activation and 
cancer development.  Additional testing of DNA, RNA, or protein biomarkers related to 
the function of GSK3052230 may be done if ongoing research identifies or defines 
additional biomarkers for therapy failure or predictive and prognostic biomarkers. 
Paired pre- and post-dose fresh biopsies will be obtained from a minimum of 6 subjects 
with accessible tumors in Arm C.  These biopsies will be taken during the screening 
period, e.g., within 7 days prior to treatment (preferably pre-dose on day 1), and on Day 9 
in those subjects who have signed the corresponding section of the informed consent. A 
biopsy is also required, when feasible, upon disease progression.  The timing of the 
collections may be adjusted on the basis of emerging pharmacokinetic or 
pharmacodynamic data from this study or other new information in order to ensure 
optimal evaluation of the pharmacodynamic endpoints.  Details of the tumor biopsy 
collection including processing, storage and shipping procedures will be provided in the 
SPM.
7.7.1. Determination of Deregulation Central Confirmation of FGF Signaling
Signalling Pathway Status and Translational Research
A requirement for inclusion into this study is deregulated FGF pathway signaling (e.g. 
FGFR gene amplification) in tumor tissue. As part of the development and validation of 
this assay, additional measures to FGFR1 gene amplification will be collected to 
determine if these increase the discriminatory potential of the assay for future 
development of the IUO. Tumor alterations, such as FGFR1 gene amplification testing, 
will be conducted using a certified laboratory (e.g. CLIA or appropriate certification) and 
validated laboratory developed test (LDT) in a central laboratory. In addition, an 
exploratory objective of this study is to develop and further validate the deregulated FGF 
pathway signaling assay towards an investigational use only (IUO) assay that can be used 
for future subject selection and for regulatory approval and registration. The regulatory 
approved assay will be used in the future to precisely identify the specific deregulated 
FGF signaling marker such as FGFR gene amplification or over expression, FGF ligand 
overexpression, etc., status in subjects who may benefit from treatment with 
GSK3052230. It is essential that the required amount of tumor tissue is obtained in order 
to perform the FISH assay for entry into the study in Arms A and B, explore other 
potential measures of FGF signaling pathway deregulation, and complete the necessary 
equivalency and precision testing requirements for the development of an IUO.
Collection of archival primary tumor tissue is required for all subjects (see Time and 
Events Table; Section 7.1;); if not available a fresh sample will be required. A formalin 
fixed paraffin embedded tumor block is requested or if not available, approximately 15 
sections will be needed. Details of the tumor biopsy collection including amount, 
processing, storage, and shipping procedures will be are provided in the SPM.
In addition, these samples may be Arms A and B, a requirement for inclusion is 
evidence of FGFR1 gene amplification in tumor tissue as determined by a central 
laboratory (CLIA or appropriate certification) using a laboratory developed test.


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In Arm C, FGF2 expression will be evaluated for the markers retrospectively by IHC 
to determine if expression levels of FGF2 are associated with response to 
GSK3052230
Any remaining tissue from this study may be used for:
•
Development and validation of a potential IUO assay and companion 
diagnostic test, e.g., FGFR1 gene amplification by FISH or FGF2 expression by 
IHC.
•
Alternative biomarkers of FGF pathway signalling. 
•
Biomarker research (protein, RNA and DNA) and status of RTK/PI3K/AKT 
pathways and cancer development and additional testing of DNA, RNA, or protein 
biomarkers related to the function of GSK3052230 if ongoing research identifies or 
defines additional predictive and prognostic biomarkers.
Samples will be collected as indicated It is essential that the required amount of 
tumor tissue is obtained in the Timeorder to perform the FISH assay for entry into 
the study in Arms A and Events Table (Section ). After determination B, explore other 
potential measures of FGF signaling pathway alterations, tissue deregulation in all 
arms including Arm C, and complete the necessary equivalency and precision 
testing requirements for the development of an IUO and potential companion 
diagnostic test.
Tissue samples/sections will be retained for the further confirmation using the IUO 
validated assay or potential companion diagnostic test, when available.  All samples 
will be retained for a maximum of 15 years after the last subject completes the trial.
Section 7.7.2.1 Plasma for Soluble Markers
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
Clusters of markers (e.g. cytokines and angiogenic factors [CAF]) circulating in the 
plasma have been found to correlate with tumor pathway activation. Soluble 
mesotheline-related peptides (SMRP) have been shown to be clinical markers of 
MPM.... Therefore, a broad panel of CAF, including FGF ligand, and SMRP will be 
evaluated....
Section 7.7.2.2 Circulating cell free DNA (CFDNA) Analysis
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
...will be analyzed for mutations in genes relevant to RTK/MAPK/PI3K pathway and 
cancer biology in cell free DNA...
Section 10.1.2 Male Subjects
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)


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For male subjects in Arm A and B, to prevent pregnancy in a female partner…
For male subjects in Arm C, there are no contraception restrictions.
Section 11 Data Management
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
Patient reported data will be collected via paper questionnaires and will be entered 
into the eCRF centrally. Data will be checked for completeness by study staff 
immediately after completion by the subject and reasons for non-compliance will be 
noted.
Section 12.1 Considerations of statistical design
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
The sections below show the planned dose cohorts as well as the decision rules, by study 
arm, specifying the number of subjects with a confirmed objective response (according to 
RECIST 1.1) needed for continuing enrolment, or stopping for futility, and stopping for 
efficacy.  The methodology is based on the predictive probability of success if enrolment 
continues to 30 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 but the predictive probability design allows for evaluation of stopping rules
futility after each every subject rather than once a minimum enrolment has been 
reached whereas the Green-Dahlberg design does this at only two stages one fixed 
interim and that the predictive probabilities methodology allows for stopping for success 
as well as for futility. at the end of enrolment. 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.  A randomized Phase II or Phase III study may be conducted based on 
the results from this study
Section 12.2 Hypotheses
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
No formal statistical hypotheses are being tested during the dose escalation portions of 
Arms A, B, and B or for Arm C.  Analysis of the data obtained from the dose escalation 
parts of Arms A and B the study will be focused...
For the dose expansion portions of Arms A and B the study, hypothesized response 
rates...
Section 12.3.1 Arm A: GSK3052230 + Paclitaxel + Carboplatin
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)


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Starting with a cohort of 12 subjects and allowing for a maximum sample size of 30, this 
design will have a type I error rate (α) of 0.15 and 88% power.  The trial is designed to 
stop early for efficacy when the predictive probability of success if the trial were to 
continue to the total sample size of 30 is greater than or equal to 90%.11 and 86% 
power.  The trial is stopped early for futility if the predictive probability of success is less 
than 0.1%.  The Bayesian prior used in determining the design was Beta (0.3, 0.7), a 
relatively non-informative prior with a mean response rate of 30%.  Under the null 
hypothesis, the expected sample size is 22.724.2 subjects and probability of early 
termination (PET) is 9483.5%. Under the alternative hypothesis, the expected sample size 
is 1729.7 subjects and the probability of early termination PET is 94.69%.
Section 12.3.2 Arm B: GSK3052230 + Docetaxel
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
An initial dose escalation will be used to establish the MTD. Once the final dose is 
confirmed, at least 1214 and up to 30 subjects...
Starting with a cohort of 1214 subjects and allowing for a maximum sample size of 30, 
this design will have a type I error rate (α) of 0.0907 and 8179% power.  The trial is 
designed to stop early for efficacy when the predictive probability of success if the trial 
were to continue to the total sample size of 30 is greater than or equal to 90%.  The trial 
is stopped early for futility if the predictive probability of success is less than 0.1%.  The 
Bayesian prior used in determining the design was Beta (0.15, 0.85), a relatively non-
informative prior with a mean response rate of 15%.  Under the null hypothesis, the 
expected sample size is 24.0 subjects and probability of early termination is 84.5%. 
Under the alternative hypothesis, the expected sample size is 29.5 subjects and the 
probability of early termination is 12.2%.
Section 12. Arm C: GSK3052230 + Pemetrexed + Cisplatin
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
12.3.3. Arm C: GSK3052230 + Pemetrexed + Cisplatin
An initial dose escalation will be used to establish the MTD. Once the final dose is 
confirmed, at least 12 and up to 30 subjects in total will be enrolled at that dose, 
using decision rules defined in Section 4.2.3.  The assumptions underlying the design 
are detailed below and are based on previously published randomized phase 3 data 
in the 1st line setting of malignant pleural mesothelioma [Vogelzang, 2003].
The null hypothesis is:
H0: p≤40%
The alternative hypothesis is:
HA:p≥60%


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Starting with a cohort of 12 subjects and allowing for a maximum sample size of 30, 
this design will have a type I error rate (α) of 0.10 and 82% power.  The trial is 
stopped early for futility if the predictive probability of success is less than 0.1%.  
The Bayesian prior used in determining the design was Beta (0. 5, 0.5), a relatively 
non-informative prior with a mean response rate of 50%.  Under the null hypothesis, 
the expected sample size is 23.1 subjects and probability of early termination (PET) is 
92.386.4%. Under the alternative hypothesis, the expected sample size is 19.129.5
subjects and the probability of early termination PET is 90.613.7%.
12.3.3. Arm C: GSK3052230
A sample size of 18-20 subject is based on the first futility decision timepoint for a test of 
the null hypothesis HO:p≤5% vs HA: p≥20% again using predictive probability design. 
This arm will not stop for success, but will stop for futility if no responses are observed in 
18 subjects.
Section 12.7 Interim Analysis
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
For each study arm, after the initial 12 (Arms A and C) or 14 (Arm B) subjects have 
enrolled at the final dose, response data will be reviewed on an ongoing basis and the 
number of responses observed will be compared with the stopping rules provided in 
Section 4.2.1 (Arm A), Section 4.2.2 (Arm B), and Section 4.2.3. and Section (Arm C).  
The rules are also shown in a tabular format below:
TABLE 14: Deleted right hand column for stopping for success.
TABLE 15: Deleted right hand column for stopping for success. Deleted top 2 rows for 
12 and 13 patients.
FIGURE 2 and FIGURE 3: Deleted figures because no longer stopping for success.
TABLE 16: Added new table for Arm C.
Section 12.8.2.2 Adverse Events
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
For the dose-escalation portions of Arms A and B the study, dose-limiting toxicities...
Section 12.8.3 Patient Reported Outcomes
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
12.8.3. Patient Reported Outcomes
Change from baseline scores in LCSS and LCSS-meso will be calculated for all 
scales and timepoints. 10mm in change from baseline were previously identified as 
clinically meaningful (P. Hollen, personal communication). Associations with 


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efficacy assessments and between patient reported and clinician reported 
symptomatic will be explored when warranted. Further details will be provided in 
the RAP.
Section 12.8.5.
Pharmacokinetic/Pharmacodynamic Analyses
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
Where evidence of activity is seen, linear and/or non-linear mixed effect models may be 
fitted to the data to estimate PKPDPK/PD parameters of interest (e.g. slope, baseline 
(E0), location concentration for 50% of maximum effect (EC50) and maximum effect 
(Emax)).
Section 12.8.6 Tumor Kinetics Analysis
REVISED TEXT: (new text bold and underlined, deleted text in strikethrough)
Data from all some arms of the study...


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Amendment 2
Where the Amendment Applies
This amendment applies to all sites.
Summary of Amendment Changes with Rationale
Amendment No.2: Sponsor medical monitor information was updated, the inclusion 
criterion for FGFR gene amplification was modified, clarifications were made to the 
Time and Events Table, vital sign measurements, and permitted concomitant 
medications; and male contraceptive requirements were corrected.
List of Specific Changes
Change 1: Inclusion criterion for FGFR gene amplification modified.
Section3.2.1 Inclusion Criteria
PREVIOUS TEXT:
3. Availability of archival tumor tissue required for assessment of deregulated FGF 
pathway signaling e.g. FGFR1 amplification or FGF2 over expression status based on 
emerging GSK3052230 preclinical data), provided no systemic therapy has been 
given since the biopsy was obtained. If archival tissue is not available, a fresh biopsy 
is required. Please refer to Section 7.7.1.2.  In Arms A and B, subjects will be 
prospectively screened for FGFR1 gene amplification using a FISH assay. For 
inclusion in this study, a ratio of FGFR1/CEN 8 of > 2 will be required. FGFR1 gene 
amplification will determined by central laboratory testing.
REVISED TEXT: (new text underlined, deleted text in strikethrough)
3. Availability of archival tumor tissue required for assessment of deregulated FGF 
pathway signaling e.g. FGFR1 amplification or FGF2 over expression status based on 
emerging GSK3052230 preclinical data), provided no systemic therapy has been given 
since the biopsy was obtained. If archival tissue is not available, a fresh biopsy is 
required. Please refer to Section 7.7.1.2.  In Arms A and B, subjects will be 
prospectively screened for FGFR1 gene amplification using a FISH assay (note, local 
testing is permitted for pre-screening of subjects prior to central testing). For 
inclusion in this study, based on the central laboratory testing, FGFR1 gene 
amplification must meet one of the following criteria: a ratio of FGFR1/CEN 8 of ≥2; 
or average number of FGFR1 signals per tumor nucleus of ≥6; or the percentage 
of tumor nuclei containing  ≥5 FGFR1 signals is ≥50%. FGFR1 gene amplification 
will determined by central laboratory testing.


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Change 2: Clarification for stage of disease and chemotherapy in Arm A.
Protocol Synopsis, Section3.2.1 Inclusion Criteria
PREVIOUS TEXT:
2.
Histologically or cytologically confirmed diagnosis:
Arms A and B: Stage IV squamous NSCLC...
Arm A: Subjects who have received no prior therapy for Stage IV disease....
Arm B: Subjects who have ... Stage IV disease...
Arm C: Subjects who have ... Stage IV disease...
REVISED TEXT: (new text underlined, deleted text in strikethrough)
2.
Histologically or cytologically confirmed diagnosis:
Arms A and B: Stage IV or recurrent metastatic squamous NSCLC...
Arm A: Subjects who have received no prior therapy for Stage IV or recurrent 
metastatic disease....
Arm B: Subjects who have ... Stage IV or recurrent metastatic disease...
Arm C: Subjects who have ... Stage IV or recurrent metastatic disease...
PREVIOUS TEXT:
2.
Arm A: Subjects who have received no prior therapy for Stage IV disease. Note, to 
avoid any undue delay of initiating systemic chemotherapy for these subjects with 
newly diagnosed metastatic disease, it is allowed to initiate the first cycle of 
chemotherapy while the subject is still in screening for the present study. The first 
dose of GSK3052230 should then be given no later than the day of the second cycle 
of chemotherapy.
REVISED TEXT: (new text underlined, deleted text in strikethrough)
2.
Arm A: Subjects who have received no prior therapy for Stage IV or recurrent 
metastatic disease. Note, to avoid any undue delay of initiating systemic 
chemotherapy for these subjects with newly diagnosed metastatic disease, it is 
allowed to initiate the first cycle of chemotherapy whilst the subject is still in 
screening for the present study while eligibility for the study is still being 
determined, as long as the first dose of GSK3052230 is given no later than 
Cycle 2 Day 1 of chemotherapy.


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Section 4.2.1 Arm A
PREVIOUS TEXT:
Arm A: Screening procedure for subjects on chemotherapy
To avoid any undue delay in initiating systemic chemotherapy for subjects with newly 
diagnosed Stage IV disease, the first cycle of chemotherapy may be initiated while 
subjects are still in screening for the present study.  
REVISED TEXT: (new text underlined, deleted text in strikethrough)
Arm A: Screening procedure for subjects on chemotherapy
To avoid any undue delay in initiating systemic chemotherapy for subjects with newly 
diagnosed Stage IV or recurrent metastatic disease, the first cycle of chemotherapy 
may be initiated while subjects are still in screening determination of eligibility is being 
completed for the present study.
Change 3: Other clarifications to Inclusion/Exclusion criteria.
Section3.2.1 Inclusion Criteria
10. Added footonotes for hemoglobin (a) and serum total bilirubin (b):
a. Subjects should meet criteria in the absence of hematopoetic growth factors 
or transfusions.
b. If the serum total bilirubin is elevated at screening but the direct bilirubin is 
≤ULN then the subject may be allowed to enter study.
Section3.2.2 Exclusion Criteria
PREVIOUS TEXT:
10.
Symptomatic leptomeningeal or brain metastases or spinal cord compression.
NOTE: Subjects previously treated for these conditions that have had stable CNS disease 
(verified with consecutive imaging studies) for >1 month, are asymptomatic and off 
corticosteroids, or are on stable dose of corticosteroids for at least 1 month prior to study 
Day 1 are permitted. Stability of brain metastases must be confirmed with imaging. If 
subjects have been treated with gamma knife they can be enrolled 2 weeks post-
procedure as long as there are no post-procedure complications. In addition, subjects 
treated or currently taking enzyme-inducing anticonvulsant are allowed on study.
REVISED TEXT: (new text underlined, deleted text in strikethrough)
10. Symptomatic leptomeningeal or brain metastases or spinal cord compression.
NOTE: Subjects previously treated for these conditions are eligible if they meet 
both of the criteria below:


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(1) have had stable CNS disease for at least 4 weeks after local therapy as 
assessed by imaging (contrast enhanced magnetic resonance imaging (MRI) or 
computed tomography (CT)), and
(2) are asymptomatic and off corticosteroids, or are on stable dose of 
corticosteroids for at least 4 weeks prior to Day 1.
Change 4: Clarifications to preparation of GSK3052230, Time and Events 
Table, vital sign measurements, permitted concomitant medications.
Section 5.2 Preparation/Handling/Storage of GSK3052230
Added to end of paragraph on Preparation:
Please refer to SPM for recommended IV supplies.
Section 7.1 Time and Events Table (footnotes)
PREVIOUS TEXT:
Visit Window
Must occur within the window specified. D=day
Physical exam, weight, and height (baseline only)
Complete physical exam at 
screening. Abbreviated disease-oriented physical exam subsequently.
Ophthalmologic Exam
To be performed by ophthalmologist.
Vital Signs
Within -20/+10mins of GSK3052230 i.v. Arm A: -10mins of i.V. 
start
Hematology and Chemistry
See Table 11 for analytes. In addition Arm A: additional 
cycles D8 while dosing on paclitaxel + carboplatin only
Circulating Biomarkers 
Plasma sample collected predose. 
Blood sample for PGx
Collect only if PGx informed consent has been signed. 
Brain Scan
within 8 weeks of C1D1
Bone Scan
within 12 weeks of C1D1
ARM A: Paclitaxel + Carboplatin 
GSK3052230 infused & observed 1 hr prior to 
chemotherapy doses.
REVISED TEXT: (new text underlined, deleted text in strikethrough)
Visit Window
Tissue prescreen for Arms A and B within 60 days and all 
other screening assessments within 30 days of C1D1. Visit windows of ±2 days during 
study through EOT, +7 days for F/U. Cycle 1 Day 9 assessments for Arm C only.


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Physical exam, weight, and height (baseline only)
Not needed C1D1 if screening 
assessments within prior 72 hrs. Complete physical exam at screening. Abbreviated 
disease-oriented physical exam subsequently.
Ophthalmologic Exam
To be performed by ophthalmologist or qualified 
optometrist.
Vital Signs
Arms A + B: Within 20 min before start of first chemotherapy 
infusion and within 20 min before start of GSK3052230 infusion. Arm C: Before 
start of GSK3052230 infusion
Hematology and Chemistry
Not needed C1D1 if screening assessments within prior 
72 hrs. See Table 11 for analytes. In addition Arm A: additional cycles D8 while dosing 
on paclitaxel + carboplatin only
Circulating Biomarkers 
Plasma sample collected predose (+7 days prior to C1D1)
Blood sample for PGxCollect any time on study but only if PGx informed consent has 
been signed; preferred on C1D1 after dosing.
Brain Scan
within 35 days of C1D1
Bone Scan
within 4 weeks of C1D1
ARM A: Paclitaxel + Carboplatin 
GSK3052230 infused & observed 1 hr prior to 
chemotherapy doses. May start chemotherapy during screening period, see inclusion 
#2
Section 7.3.3 Vital Signs
PREVIOUS TEXT:
Vital sign measurements will include systolic and diastolic blood pressure, temperature, 
respiration rate and pulse rate.  Vital signs should be measured after resting for at least 5 
minutes …. Refer to the SPM for details regarding measurement of vital signs.
REVISED TEXT: (new text underlined, deleted text in strikethrough)
Vital sign measurements will include systolic and diastolic blood pressure, temperature, 
respiration rate and pulse rate.  All vital sign measurements will be obtained after the 
subject has rested for at least 5 minutes .... Whenever blood pressure and heart rate 
are measured at the same nominal time as a blood draw, the blood pressure and 
heart rate will be prior to the blood draw. Refer to the SPM for details regarding 
measurement of vital signs
Section 7.3.6 Ophthalmologic Examinations
PREVIOUS TEXT:
These exams will be performed by an ophthalmologist and includes...


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REVISED TEXT: (new text underlined, deleted text in strikethrough)
These exams will be performed by an ophthalmologist or qualified optometrist and 
includes...
Section 9.1 Permitted Medications
PREVIOUS TEXT:
Subjects should receive full supportive care during the study, including transfusion of 
blood and blood products, and treatment with antibiotics, antiemetics, antidiarrheals, and 
analgesics, as appropriate.
REVISED TEXT: (new text underlined, deleted text in strikethrough)
Subjects should receive full supportive care during the study, including transfusion of 
blood and blood products, and treatment with antibiotics, antiemetics, antidiarrheals, and 
analgesics, as appropriate. Pre-medication for chemotherapy is allowed per 
institutional guidelines.
Change 3: Correction of contraceptive requirements.
Section 3.2.1 Inclusion Criteria
PREVIOUS TEXT:
6.
Women of childbearing potential must have a negative serum pregnancy test within 
7 days of first dose of study treatment and agree to use effective contraception, as 
defined in Section 10, during the study and for 6 months following the last dose of 
chemotherapy or 4 weeks after the last dose of GSK3052230, whichever is latest.
7.
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 10.1.2 for 
at least 2 weeks prior to administration of the first dose of study treatment and for at 
least 6 months after the last dose of chemotherapy or 4 weeks after the last dose of 
GSK3052230, whichever is latest, to allow for clearance of any altered sperm.
REVISED TEXT: (new text underlined, deleted text in strikethrough
6. Women of childbearing potential must have a negative serum pregnancy test within 7 
days of first dose of study treatment and agree to use effective contraception, as 
defined in Section 10, during the study from 14 days prior to the first dose of study 
treatment, throughout the study, and for 6 months following the last dose of 
chemotherapy or 4 weeks after the last dose of GSK3052230, whichever is latest
7. For Arm A and B: 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 10.1.2 for at least 2 weeks prior to administration of the first dose of study 
treatment and for at least 6 months after the last dose of chemotherapy or 4 weeks 


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after the last dose of GSK3052230, whichever is latest, to allow for clearance of any 
altered sperm. Arm C: No male contraception restrictions.
Section 10.1.2
PREVIOUS TEXT:
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 until 4 weeks after the last dose of GSK3052230 or 6 months after 
the last dose of chemotherapy, whichever is latest…
REVISED TEXT: (new text underlined, deleted text in strikethrough)
For male subjects in Arm A and B, 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 until 4 weeks after the last 
dose of GSK3052230 or 6 months after the last dose of chemotherapy, whichever is latest
For male subjects in Arm C, there are no contraception restrictions.


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Amendment 1
Where the Amendment Applies
This amendment is applicable to UK site(s) only.  
Summary of Amendment Changes with Rationale
Amendment No.1: This amendment modified contraceptive practice and adjusted QTc 
stopping criteria for the UK to comply with MHRA guidelines.  
List of Specific Changes
Change 1: Contraception Guidelines
RATIONALE FOR CHANGE:
The protocol has been clarified to reflect the SPC for paclitaxel, carboplatin, and 
docetaxel which recommend using effective contraception methods for a period of 
6 months.  In addition, the protocol has been clarified regarding the contraception timing 
for GSK3052230 to allow 5 half-lives for drug clearance.  The GSK3052230 half life is 
5.2 days. The protocol has been modified to implement the use of an effect contraception 
methods for 4 weeks post-therapy of GSK3052230 given there are no genotoxicity 
concerns.
Section 3.2.1 Inclusion Criteria:
PREVIOUS TEXT
6. Women of childbearing potential must have a negative serum pregnancy test within 7 
days of first dose of study treatment and agree to use effective contraception, as defined 
in Section 10, during the study and for 21 days following the last dose of study treatment.
7. For Arms A and B: 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 10.1.2 for at least 2 weeks prior to administration of the first dose of study 
treatment [and for at least 4 weeks after the last dose of chemotherapy given in this study] 
to allow for clearance of any altered sperm. Arm C: No male contraception restrictions.
REVISED TEXT: (new text underlined, deleted text in strikethrough)
6. Women of childbearing potential must have a negative serum pregnancy test within 7 
days of first dose of study treatment and agree to use effective contraception, as 
defined in Section 10, during the study and for 21 days 6 months following the last 
dose of chemotherapy or 4 weeks after the last dose of GSK3052230, whichever 
is latest.
7.    For Arms A and B: 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 10.1.2 for at least 2 weeks prior to administration of the first dose of study 


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treatment [and for at least 4 weeks 6 months after the last dose of chemotherapy or 4 
weeks after the last dose of GSK3052230, whichever is latest, to allow for clearance of 
any altered sperm. Arm C: No male contraception restrictions.
Section 7.3.8 Pregnancy Testing and Reporting:
PREVIOUS TEXT
If a female subject is of childbearing potential, she must have a serum -HCG pregnancy 
test performed within 7 days prior to the first dose of study treatments. 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 in 
Section 10.1  during the study until 25 days following the last dose of study treatments.
REVISED TEXT: (new text underlined, deleted text in strikethrough)
If a female subject is of childbearing potential, she must have a serum -HCG pregnancy 
test performed within 7 days prior to the first dose of study treatments. 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 in 
Section 10.1 during the study until 25 days 6 months following the last dose of study 
treatments chemotherapy or 4 weeks after the last dose of GSK3052230, whichever is 
latest.
Section 10.1.1 Female Subjects
Moved to end of section:
PREVIOUS TEXT
Complete abstinence from sexual intercourse for 14 days prior to first dose of study 
treatment, through the dosing period, and for at least 25 days after the last dose of study 
treatment.
REVISED TEXT: (new text underlined, deleted text in strikethrough)
Complete abstinence from sexual intercourse or contraception must be practiced for 
14 days prior to first dose of study treatment, through the dosing period, and for at least 
25 days 4 weeks after the last dose of study treatment GSK3052230 or 6 months after 
the last dose of chemotherapy, whichever is latest.
Section 10.1.2 Male Subjects
PREVIOUS TEXT
For subjects on Arm A and B, 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…..
For subject in Arm C, there are no restrictions.


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REVISED TEXT: (new text underlined, deleted text in strikethrough)
For subjects on Arm A and B, 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 until 4 weeks after the 
last dose of GSK3052230 or 6 months after the last dose of chemotherapy, 
whichever is latest…..
For subject in Arm C, there are no restrictions.
Change 2: QTc stopping rules for the UK
RATIONALE FOR CHANGE:
Country Specific Requirements previously specified the QTc stopping criteria as 
500msec for France.  The QTc stopping rules and the Country specific appendix have 
been modified to include UK along for France for the QTc stopping criteria to comply 
with the MHRA guidelines.  
Section 4.7.2, QTc Stopping Criteria
PREVIOUS TEXT
For subjects recruited in France, please refer to Appendix 7 for the French specific QTc 
stopping criteria.
REVISED TEXT (new text underlined, deleted text in strikethrough):
For subjects recruited in France or the UK, please refer to Appendix 7 for the French 
country specific QTc stopping criteria.
15.8 Appendix 7: Country Specific Requirements
PREVIOUS TEXT
France:
French Specific QTc Stopping Criteria:
In line with local requirements, a French subject that meets the criteria QTc1 below will 
have study treatment withheld...
REVISED TEXT (new text underlined, deleted text in strikethrough):
France or UK:
French or UK Specific QTc Stopping Criteria:


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In line with local requirements, French subjects that meet the criteria QTc1 below will 
have study treatment GSK3502230 withheld:
QTcB > 500 msec
In line with local requirements, UK subjects that meet the criteria QTc1 below will 
have study treatment withheld:
QTc > 500 msec
1Based on average corrected QT (QTc) interval value of triplicate electrocardiograms 
(ECGs) to include manual over-read. For example, if an ECG demonstrates a prolonged 
QT interval, obtain 2 more ECGs over a brief period, and then use the averaged QTc 
values of the 3 ECGs to determine whether the subjects should have study treatment
GSK3502230 withheld.
QT interval (corrected for HR) ≥500 msec; GSK3502230 will be permanently 
discontinued.
QTc interval increase from baseline ≥ 60 msec and maximum QTc  < 500 msec; 
GSK3502230 may be restarted at a reduced dose level after discussion with the 
medical monitor once the QTc returns to baseline.  If QTc prolongation meeting 
stopping criteria recurs after re-challenge, GSK3502230 must be permanently 
discontinued.
If the QTc prolongation resolves to Grade 1 or baseline, the subject may be re-started on 
study treatment GSK3502230 if the investigator and GSK Medical Monitor agree that the 
subject will benefit from further treatment

SAP_001.pdf: 
CONFIDENTIAL
GlaxoSmithKline Group of Companies
FGF117360
1
Division: World Wide Development
Retention Category: GRS019
Information Type: Reporting and Analysis Plan
Title:
Reporting and Analysis Plan for FGF117360, Multi-arm, Non-
randomized, Open-Label Phase IB Study to Evaluate 
GSK3052230 in Combination with Paclitaxel and Carboplatin, 
or Docetaxel or as Single Agent in Subjects with Solid 
Malignancies and Deregulated FGF Pathway Signaling
Compound Number:
GSK3052230 (FP-1039)
Effective Date:
01-MAR-2017
Description: The purpose of this reporting and analysis plan (RAP) is to describe the 
planned analyses and output to be included in the Clinical Study Report for Protocol 
FGF117360.  This RAP is intended to describe the safety, pharmacokinetics, 
pharmacodynamics, and anti-tumor activity analyses required for the study. This 
document will be provided to the study team members to convey the content of the 
Statistical Analysis Complete (SAC) deliverable.
Subject: Oncology, Reporting and Analysis Plan, GSK3052230, Combination, Dose 
Escalation, NSCLC, Mesothelioma, predictive probability design
Author’s Name, Title and Functional Area:
Manager Statistics, Clinical Statistics 
 Director Clinical Pharmacology, CPMS
 Principal Programmer, Clinical Programming
Approved by (approval documented via e-mail): 
28-FEB-2017
Director, Statistics and Programming
Clinical Statistics
Copyright 2017 the GlaxoSmithKline group of companies. All rights reserved. 
Unauthorised copying or use of this information is prohibited.
PPD
PPD
PPD
PPD


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TABLE OF CONTENTS
PAGE
ABBREVIATIONS ...........................................................................................................5
1.
INTRODUCTION......................................................................................................7
2.
STUDY OBJECTIVES AND ENDPOINTS................................................................8
2.1.
Primary.........................................................................................................8
2.2.
Secondary ....................................................................................................9
2.3.
Exploratory .................................................................................................10
2.4.
Statistical Hypotheses.................................................................................10
2.4.1.
Arm A: GSK3052230 + Paclitaxel + Carboplatin ..........................11
2.4.2.
Arm B: GSK3052230 + Docetaxel................................................11
2.4.3.
Arm C: GSK3052230 + Pemetrexed + Cisplatin...........................11
3.
STUDY DESIGN ....................................................................................................11
4.
PLANNED ANALYSES ..........................................................................................13
4.1.
Analyses.....................................................................................................13
4.1.1.
Dose Escalation 3+3 Design........................................................13
4.1.2.
Interim Analysis for Futility/Efficacy Review .................................13
4.2.
Final Analyses ............................................................................................17
5.
SAMPLE SIZE CONSIDERATIONS.......................................................................17
5.1.
Sample Size Assumptions ..........................................................................17
5.1.1.
Arm A: GSK3052230 + Paclitaxel + Carboplatin ..........................17
5.1.2.
Arm B: GSK3052230 + Docetaxel................................................18
5.1.3.
Arm C: GSK3052230 + Pemetrexed + Cisplatin...........................18
5.2.
Sample Size Sensitivity...............................................................................18
5.3.
Sample Size Re-estimation.........................................................................18
6.
ANALYSIS POPULATIONS ...................................................................................18
6.1.
All Treated Subjects....................................................................................18
6.2.
All Evaluable Subjects Population...............................................................18
6.3.
Pharmacokinetic Population........................................................................19
6.4.
Pharmacodynamic Population ....................................................................19
6.5.
Assay Validation Population........................................................................19
6.6.
Analysis Datasets .......................................................................................19
7.
TREATMENT COMPARISONS..............................................................................19
7.1.
Data Display Treatment and Other Subgroup Descriptors ..........................20
8.
GENERAL CONSIDERATIONS FOR DATA ANALYSES.......................................20
8.1.
Multicenter Studies .....................................................................................21
8.2.
Other Strata and Covariates .......................................................................22
8.3.
Examination of Subgroups..........................................................................22
8.4.
Multiple Comparisons and Multiplicity .........................................................22
9.
DATA HANDLING CONVENTIONS .......................................................................22
9.1.
Premature Withdrawal and Missing Data ....................................................22
9.2.
Derived and Transformed Data...................................................................22


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9.2.1.
Reference dates ..........................................................................23
9.2.2.
Study Day for Safety and Efficacy Measures ...............................23
9.2.3.
Duration and Elapsed Time .........................................................23
9.2.4.
Imputation of Partial Dates...........................................................24
9.2.5.
Baseline Definition.......................................................................30
9.2.6.
Change from baseline..................................................................30
9.2.7.
Multiple Assessments ..................................................................30
9.2.8.
Actual Treatment .........................................................................31
9.2.9.
Treatment Cycle ..........................................................................31
9.2.10.
Extended Loss to Follow-up or Extended Time without an 
Adequate Assessment.................................................................32
9.2.11.
Date Associated with Response ..................................................32
9.2.12.
Cardiac Scan Modalities (ECHO/MUGA) .....................................32
9.2.13.
Derived and Transformed Variables.............................................33
9.3.
Study Time Periods ....................................................................................34
9.3.1.
Time in Relation to Treatment......................................................34
9.3.2.
Study Time Periods for Concomitant Medications Blood 
and Blood Supportive Care Products...........................................34
9.4.
Values of Potential Clinical Importance.......................................................35
9.4.1.
Laboratory Parameters ................................................................35
9.4.2.
ECG Parameters: ........................................................................36
9.4.3.
Vital Signs....................................................................................36
9.4.4.
Left Ventricular Ejection Fraction .................................................37
10. STUDY POPULATION...........................................................................................38
10.1.
Disposition of Subjects................................................................................38
10.2.
Protocol Deviations.....................................................................................38
10.3.
Demographic and Baseline Characteristics.................................................38
10.4.
Concomitant Medications............................................................................39
11. EFFICACY .............................................................................................................39
12. SAFETY ANALYSES .............................................................................................44
12.1.
Extent of Exposure .....................................................................................44
12.2.
Adverse Events...........................................................................................45
12.3.
Adverse Events of Special Interest .............................................................46
12.4.
Deaths and Serious Adverse Events...........................................................47
12.5.
Adverse Events Leading to Discontinuation of Study Treatment 
and/or Withdrawal from the Study and Other Significant Adverse 
Events ........................................................................................................47
12.6.
Pregnancies................................................................................................47
12.7.
Clinical Laboratory Evaluations...................................................................48
12.7.1.
Analyses of Liver Function Tests .................................................49
12.8.
Other Safety Measures...............................................................................50
13. HEALTH OUTCOMES ANALYSES........................................................................52
14. PHARMACOKINETIC ANALYSES.........................................................................54
14.1.
Drug Concentration Measures ....................................................................54
14.2.
Deriving and Summarizing Pharmacokinetic Parameters............................55
14.3.
Population Pharmacokinetic Analyses ........................................................55


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FGF117360
4
15. PHARMACOKINETIC/PHARMACODYNAMIC ANALYSES ...................................55
16. IMMUNOGENECITY ANALYSES ..........................................................................56
17. TRANSLATIONAL RESEARCH .............................................................................56
17.1.
FGF Biomarkers Analyses ..........................................................................56
17.1.1.
FGFR1 Gene Amplification Assay................................................57
17.1.2.
FGF2 Immunohistochemistry Assay ............................................58
18. PHARMACOGENETICS ........................................................................................59
19. REFERENCES.......................................................................................................60
20. APPENDICES........................................................................................................61
20.1.
Appendix 1: Data Displays..........................................................................61
20.1.1.
Study Population Tables..............................................................61
20.1.2.
Efficacy Tables ............................................................................62
20.1.3.
Efficacy Figures ...........................................................................63
20.1.4.
Safety Tables...............................................................................63
20.1.5.
Safety Figures .............................................................................71
20.1.6.
Pharmacokinetics Tables.............................................................72
20.1.7.
Pharmacokinetics Figures............................................................72
20.1.8.
Pharmacodynamic Tables ...........................................................74
20.1.9.
Pharmacodynamic Figures ..........................................................74
20.1.10. ICH Listings .................................................................................75
20.1.11. Other Listings ..............................................................................80
20.2.
Appendix 2: Pharmacogenetics (PGx) ........................................................83


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5
Abbreviations
AE
Adverse Event
ATC
Anatomical Therapeutic Chemical
CI
Confidence Interval
CONMED
Concomitant Medication Dataset
CPMS
Clinical Pharmacology, Modeling and Simulation
CR
Complete Response
CTCAE
Common Terminology Criteria for Adverse Events
CTX
Anti-cancer Therapy Dataset
DISCHA1
Disease Characteristics Dataset
ECG
Electrocardiogram
ECHO
Echocardiogram
ECOG
Easter Cooperative Oncology Group
eCRF
Electronic Case Report Form
GHO
Global Health Outcomes
GSK
GlaxoSmithKline
HR
Hazard Ratio
IDMC
Independent Data Review Committee
IDSL
Integrated Data Standards Library
ITT
Intent to Treat
LCSS
Lung Cancer Symptom Score
LDH
Lactate Dehydrogenase
LLN
Lower Limit of Normal
LVEF
Left Ventricular Ejection Fraction
MedDRA
Medical Dictionary for Medical Affairs
MPM
Malignant Pleural Mesothelioma
NCI
National Cancer Institutes
NSCLC
Non-Small Cell Lung Cancer
ONCTTE
Oncology Time to Event Dataset
ONCSURV
Oncology Survival Dataset
ORR
Overall Response Rate
OS
Overall Survival
PD
Progressive Disease
PFS
Progression-free Survival
PGx
Pharmacogenetics
PK
Pharmacokinetics
PR
Partial Response
PT
Preferred Term
RAMOS
Registration and Medication Ordering System
RADIO
Radiotherapy Dataset
RAP
Reporting and Analysis Plan


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FGF117360
6
RECIST
Response Evaluation Criteria in Solid Tumors
RESP2
Best Response Dataset
SAE
Serious Adverse Event
SD
Stable Disease
SOC
System Organ Class
SRT
Safety Review Team
ULN
Upper Limit of Normal
Trademark Information
Trademarks of the GlaxoSmithKline 
group of companies
Trademarks not owned by the 
GlaxoSmithKline group of companies
NONE
Alimta
Paraplatin
Platinol
SAS
Taxol
Taxotere


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FGF117360
7
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 FGF117360.
Protocol Revision Chronology:
2013N165256_00
2013-APR-16
Original
2013N165256_01
2013-OCT-17
This amendment is a country-specific 
amendment for the UK. Stopping criteria 
based on QTc interval and contraceptive 
requirements have been revised.
2013N165256_02
2013-NOV-07
This amendment applies to all sites. 
Sponsor medical monitor information was 
updated, the inclusion criterion for FGFR 
gene amplification was modified, 
clarifications were made to the Time and 
Events Table, vital sign measurements, 
and permitted concomitant medications; 
and contraceptive requirements were
corrected.
2013N165256_03
29-JAN-2014
This amendment changed Arm C of the 
protocol from GSK3052230 monotherapy 
of subjects with solid tumors to 
combination chemotherapy (GSK3052230 
plus pemetrexed and cisplatin) of subjects 
with mesothelioma. Associated additions 
to the protocol include safety precautions 
for pemetrexed and cisplatin, use of 
modified RECIST for evaluation of 
clinical response, assessment of forced 
vital capacity. Patient reported outcomes 
using the Lung Cancer Symptom Scale 
(LCSS) was added for subjects with lung 
cancer and LCSS-meso for subjects with 
mesothelioma. Additional background and 
rationale were added. Stopping rules and 
sample size were modified. Translational 
research objectives were clarified.
2013N165256_04
2014-FEB-03
A minor correction to Amendment 3 was 
made on Page 24 to correct ototoxicity 
monitoring for consistency with the 
changes listed on page 114. As 
Amendment 3 was published prior to 


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FGF117360
8
Protocol Revision Chronology:
discovery of this inconsistency, the 
correction increases the document number 
from 03 to 04.
2013N165256_05
2017-FEB-17
This amendment added immunogenicity 
analyses section (Section 16) and added 
details for FGF biomarker analyses in the 
translational research section (Section 17). 
Clarifications were made to the definition 
and summary statistics for duration of 
dose delays. In addition, updates were 
made to the definition of study time 
periods.
This reporting and analysis plan (RAP) details all planned analyses required for a Clinical 
Study Report of study FGF117360. This is a phase IB study to characterize the safety and 
tolerability of GSK3052230 in combination with chemotherapy regimens and to assess 
the overall response rate (ORR) in each treatment arm. The study is composed of three 
separate treatment arms (A-C) with different study populations and chemotherapy 
regimens in combination with GSK3052230.  GSK3052230 is combined with paclitaxel 
+ carboplatin in previously untreated metastatic squamous NSCLC (Arm A), with 
docetaxel in metastatic squamous NSCLC that has progressed after 1 line of 
chemotherapy (Arm B), or with pemetrexed + cisplatin in malignant pleural 
mesothelioma (MPM) previously untreated with chemotherapy or investigational agents 
(Arm C). Within each study arm, expansion cohorts of 12-30 subjects are planned with 
futility rules based on a predictive probability design.
For further information on the study design, see the protocol (document number listed 
above).
The content of this RAP is based on the SOP and Information for Authors: Reporting and 
Analysis Plans (SOP_54838/GUI_137354) effective 23 March 2011.
All decisions regarding final analysis, as defined in this RAP document, have been made 
prior to Database Freeze of the study data. Interim analyses are detailed within Section 
4.1, where applicable.
2.
STUDY OBJECTIVES AND ENDPOINTS
2.1.
Primary
Objectives
Endpoints
Primary
To characterize the safety and tolerability 
of GSK3052230 in combination with 
Measurements used to evaluate safety 
and tolerability will include rate and 
severity of AEs, withdrawals due to AEs, 


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FGF117360
9
Objectives
Endpoints
chemotherapy regimens.
dose interruptions and reductions, 
treatment duration, and DLTs as well as 
change from baseline for the following: 
physical examinations, vital signs,:12-lead 
ECGs, ECHO, clinical laboratory tests.
To determine the regimen of 
GSK3052230 in combination with 
chemotherapy for evaluation in future 
studies based on the maximum tolerated 
dose (or maximum feasible dose).
Maximum tolerated dose (MTD) or 
maximum feasible dose (MFD).
To assess the overall response rate 
(ORR) in each treatment arm.
Best response defined as complete or 
partial response, stable disease or 
progressive disease according to RECIST 
1.1 or modified RECIST (for MPM)
ORR defined as the proportion of subjects 
with investigator-assessed confirmed 
complete response or partial response per 
RECIST 1.1 or modified RECIST (for 
MPM)
2.2.
Secondary
Objectives
Endpoints
Secondary
To assess progression free survival 
(PFS) for each treatment arm. 
PFS is defined as the interval between first 
dose of GSK3052230 and the earliest date 
of disease progression or death due to 
any cause by investigator assessment per 
RECIST 1.1 or modified RECIST (for 
MPM)
Secondary
To characterize the population 
pharmacokinetics of GSK3052230 and 
identify important determinants of 
variability.
GSK3052230 population pharmacokinetic 
parameters such as clearance (CL) and 
volume of distribution (Vd), and relevant 
covariates which may influence exposure 
(e.g. age, weight, or disease related 
covariates).
Secondary
Assess improvement in Pulmonary 
Function Tests in Patients with MPM
Change from baseline in  Forced Vital 
Capacity (FVC) in patients with MPM


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FGF117360
10
2.3.
Exploratory
Objectives
Endpoints
Exploratory
To describe the kinetics of tumor growth 
in the presence of GSK3052230 for 
each treatment arm and investigate the 
relationship between tumor growth 
kinetics and clinical activity. 
Tumor size over time, tumor growth rate 
constants, and time to tumor growth 
(TTG) predicted with the model 
parameters. Additional analysis will be 
performed utilizing volumetric analysis.
Exploratory
To identify biomarkers that may predict 
response or resistance.
Evaluate potential predictive/prognostic 
biomarkers (DNA, RNA, or protein) of 
response in circulation and/or in tumor.
Exploratory
To evaluate the pharmacodynamic
response in circulation following 
treatment.
Changes in circulating biomarkers (eg, 
proteins) implicated in FGFR or disease 
biology signalling in pre and post dose 
blood samples. 
Exploratory
To explore the relationship between PK, 
pharmacodynamic response, and 
clinical endpoints.
Predicted/observed exposure (AUC), 
trough concentrations (C), or other PK 
endpoints as compared to 
pharmacodynamic and clinical endpoints.
Exploratory
To develop and validate a Fluorescence 
in situ hybridization (FISH) -based
assay to measure FGFR1 gene 
amplification status.
Association of FGFR1 gene amplification 
with clinical response to support the 
development of an investigation use only 
test (IUO) and potential companion 
diagnostic for subject selection.
Exploratory
To investigate additional measures of 
FGF signaling pathway deregulation as 
potential predictive biomarkers for 
GSK3052230 in tissue.
Identification and validation of alternative 
measures of FGF signaling pathway 
deregulation retrospectively (eg, FGF2 
overexpression) as predictive biomarkers 
for subject selection and potential 
development of a companion diagnostic
Exploratory
To evaluate changes in patient reported 
outcomes
Change from baseline and association 
with ORR in observer and patient 
assessed components of the Lung 
Cancer Symptom Scale (LCSS) and 
LCSS-meso
Pharmacogenetics
To investigate the relationship between 
genetic variants in the host DNA and 
the pharmacokinetics of GSK3052230
and/or the relationship between genetic 
variants in the host DNA and the 
efficacy, safety and tolerability of 
GSK3052230.
Refer to Section 20.2 Appendix 2
2.4.
Statistical Hypotheses
No formal statistical hypotheses are being tested during the dose escalation portions of 
Arms A, B, and C.  Analysis of the data obtained from the dose escalation parts of the 
study will be focused on comparison between dose cohorts and only descriptive methods 
will be used in analysis of the data.


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11
Hypotheses for the dose expansion portions of the study are shown below for Arms A-C.  
2.4.1.
Arm A: GSK3052230 + Paclitaxel + Carboplatin
The null and alternative hypotheses for the overall response rate (p) are detailed below 
and are based on the most recent phase 3 evaluation of this regimen in NSCLC subjects 
including the squamous subset [Socinski, 2012].
The null hypothesis is:
H0: p≤25%
The alternative hypothesis is:
HA:p≥45%
2.4.2.
Arm B: GSK3052230 + Docetaxel
The null and alternative hypotheses for the overall response rate (p) are detailed below 
and are based on previously published randomized phase 3 data in the 2nd line setting of 
metastatic NSCLC [Hanna, 2004]. 
The null hypothesis is:
H0: p≤10%
The alternative hypothesis is:
HA:p≥25%
2.4.3.
Arm C: GSK3052230 + Pemetrexed + Cisplatin
The null and alternative hypotheses for the overall response rate (p) are detailed below 
and are based on previously published randomized phase 3 data in the 1st line setting of 
malignant pleural mesothelioma [Vogelzang, 2003].
The null hypothesis is:
H0: p≤40%
The alternative hypothesis is:
HA:p≥60%
3.
STUDY DESIGN
This study is a multi-arm, multicenter, non-randomized, parallel-group, uncontrolled, 
open-label Phase IB study designed to evaluate the safety, tolerability and preliminary 
activity of GSK3052230 in combination with paclitaxel + carboplatin (Arm A), in


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FGF117360
12
combination with docetaxel (Arm B), or in combination with pemetrexed + cisplatin 
(Arm C).  Treatment assignment information is captured on the eCRF’s.
Figure 1
Study Schema
Pemetrexed/Cisplatin +
GSK3052230
3+3 design to determine
MTD  (MFD) in subjects with MPM
Arm C
Paclitaxel/Carboplatin +
GSK3052230
N=at least 12 and up to 30 sqNSCLC
Docetaxel+ GSK3052230
3+3 design to determine MTD (MFD) 
in subjects with sqNSCLC
Docetaxel+ GSK3052230
N=at least 14 and up to 30 sqNSCLC
Arm B
Paclitaxel/Carboplatin +
GSK3052230
3+3 design to determine
MTD  (MFD) in subjects with sqNSCLC
Arm A
Pemetrexed/Cisplatin +
GSK3052230
N=at least 12 and up to 30 MPM
Dose escalation follows a 3+3 design as outlined in the Protocol Section 4.2 for 
determination of MTD (or MFD).  In each arm, dose escalation will be followed by a 
cohort expansion with stopping rules for futility based on the methodology of Lee and 
Liu (Lee, 2008).   
For Arm A, a total of at least 12 and up to 30 subjects will be enrolled at the target dose 
to further evaluate safety and efficacy. After 12 subjects have been enrolled, the number 
of observed confirmed responses will guide further enrolment according to the stopping 
rules.  The futility boundaries (inclusive) for ORR for Arm A are 0/12, 1/14, 2/17, 3/20, 
4/22, 5/24, 6/26, 7/27, 8/28, 9/29, and 10/30 subjects and are shown in tabular format in 
Section 4.1. All available data will be considered in making enrollment decisions.
For Arm B, a total of at least 14 and up to 30 subjects will be enrolled at the target dose 
to further evaluate safety and efficacy. After 14 subjects have been enrolled, the number 
of observed confirmed responses will guide further enrolment according to the stopping 
rules. The futility boundaries (inclusive) for ORR for Arm B are 0/14, 1/22, 2/26, 3/28, 
4/29, and 5/30 subjects and are shown in tabular format in Section 4.1. All available data 
will be considered in making enrollment decisions.
For Arm C, a total of at least 12 and up to 30 subjects will be enrolled at the target dose 
to further evaluate safety and efficacy. After 12 subjects have been enrolled, the number 
of observed confirmed responses will guide further enrolment according to the stopping 
rules. The futility boundaries (inclusive) for ORR for Arm C are 2/12, 3/14, 4/16, 5/18, 
6/20, 7/21, 8/23, 9/24, 10/25, 11/26, 12/27, 13/28, 14/29 and 15/30 subjects and are 
shown in tabular format in Section 4.1. All available data will be considered in making 
enrollment decisions.


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FGF117360
13
4.
PLANNED ANALYSES
As this is an open-label study, the treatment allocation (dose) is collected in the eCRF 
and this will be the treatment information used for interim and final analyses.
4.1.
Analyses
4.1.1.
Dose Escalation 3+3 Design
Review of preliminary safety and available pharmacokinetic data will be performed after 
completion of each dosing cohort. Preliminary safety data may include adverse events, 
changes in laboratory values and other safety parameters.
The GSK study team, in collaboration with study investigators, is to the review PK and 
safety data to support:
whether the dose should be escalated, and
the next dose level.
4.1.2.
Interim Analysis for Futility/Efficacy Review
During the expansion cohorts of Arms A, B, and C regular interim analyses of the 
response data will be conducted in order to determine whether the futility criteria for 
stopping the Study Arm have been met.  Study arms will not be stopped for efficacy 
based on success criteria.  
Because subjects enrol at different times, not all subjects will have been on the study long 
enough to have single or multiple disease assessments.  Since disease assessments are to 
be completed every 2 cycles during the first year of the study, we will set a cut-off date 
for inclusion in the interim analysis of subject first dose approximately 42 days (2 cycles) 
prior to the date the data are extracted.  In addition, those subjects who are ongoing and 
were enrolled prior to the cut-off date but have not had a disease assessment will not be 
included in the interim analysis.  
The study population used for decision-making at the interim analysis will be termed All 
Evaluable Subjects.  This population may include subjects who were enrolled during dose 
escalation and who received the dose used in the expansion cohort as well as those 
subjects enrolled during the expansion cohort and who meet the cut-off date requirements 
as specified above.  This will be the population for summaries of response data. The 
population of all subjects that have been enrolled at the time of the interim analysis will 
be termed the All Treated Subjects population.  This will be the population for listings of 
data.
A listing of subject responses over time will be produced.  The listing will show the 
responses observed at each timepoint for each subject along with the best confirmed 
response.  The definition of confirmed response is provided in the protocol for 
FGF117360, Section 7.4.  The study population for this display will be All Treated 
Subjects.


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FGF117360
14
In addition, a listing of subject best response by first dose date will be provided using the 
All Treated Subjects Population.  This listing will be sorted by date of first dose and will 
show whether or not each subject is ongoing, whether the subject has had at least one 
disease assessment, whether the subject is evaluable for the interim analysis, and best 
confirmed and unconfirmed response.
Summaries of best response (confirmed) and best response (unconfirmed) will be 
provided so that the study team can compare the study data to the stopping rules for 
futility and to the success rules. The population for these displays will be All Evaluable
Subjects.
A waterfall plot of response by subject as well as a bar graph of time on treatment for 
each subject will be produced.  Volumetric data may also be examined.
Stopping boundaries are based on the number of confirmed responses out of the number 
of evaluated subjects; however, subjects who are ongoing in the trial at the time of an 
interim analysis with either a non-confirmed response or stable disease may eventually 
have a confirmed response. Therefore, the total number of subjects with confirmed or 
unconfirmed responses plus those who are ongoing with stable disease should be 
compared to the futility boundary to prevent stopping the trial for futility before all 
potential confirmed responses are fully realized. Because this represents the best-case 
scenario, if this count is within the futility region, the study should be stopped.
These rules are considered guidelines for decision-making and the totality of the data will 
be considered by the team when making a decision to stop the study.
A high-level summary of the decision from the interim analysis will be provided in 
meeting minutes after the team reviews the data.  


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Table 1
Stopping Rules for Arm A: GSK3052230 + Paclitaxel + Carboplatin
Number of Evaluable 
Subjects
This Number of Objective 
Responses to Stop Early for 
Futility
12
0
13
0
14
1
15
1
16
1
17
2
18
2
19
2
20
3
21
3
22
4
23
4
24
5
25
5
26
6
27
7
28
8
29
9
30
10


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FGF117360
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Table 2
Stopping Rules for Arm B: GSK3052230 + Docetaxel
Number of Evaluable 
Subjects
This Number of Objective 
Responses to Stop Early for 
Futility
14
0
15
0
16
0
17
0
18
0
19
0
20
0
21
0
22
1
23
1
24
1
25
1
26
2
27
2
28
3
29
4
30
5


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Table 3
Stopping Rules for Arm C: GSK3052230 + Pemetrexed + Cisplatin
Number of Evaluable 
Subjects
This Number of Objective 
Responses to Stop Early for 
Futility
12
2
13
2
14
3
15
3
16
4
17
4
18
5
19
5
20
6
21
7
22
7
23
8
24
9
25
10
26
11
27
12
28
13
29
14
30
15
4.2.
Final Analyses
Final analyses will be performed after all subjects have either permanently discontinued 
study treatment or have been enrolled in the study at least 12 months (starting from the 
first day of GSK3052230) and the final study database is frozen.
5.
SAMPLE SIZE CONSIDERATIONS
5.1.
Sample Size Assumptions
The sample sizes for the dose escalation portion of Arms A-C are not determined based 
on hypothesis testing considerations. The number of subjects will be determined based in 
part on the number of cohorts required to define the MTD (or MFD).
The sample size for the expansion cohorts for Arms A-C is based on the methodology of 
Lee and Liu and the null and alternative hypotheses given in Section 2.4.
5.1.1.
Arm A: GSK3052230 + Paclitaxel + Carboplatin
Starting with a cohort of 12 subjects and allowing for a maximum sample size of 30, this 
design will have a type I error rate () of 0.11 and 86% power.  The trial is stopped early 


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FGF117360
18
for futility if the predictive probability of success is less than 0.1%.  The Bayesian prior 
used in determining the design was Beta (0.3, 0.7), a relatively non-informative prior 
with a mean response rate of 30%.  Under the null hypothesis, the expected sample size is 
24.2 subjects and probability of early termination is 83.5%. Under the alternative 
hypothesis, the expected sample size is 29.7 subjects and the probability of early 
termination is 9%.
5.1.2.
Arm B: GSK3052230 + Docetaxel
Starting with a cohort of 14 subjects and allowing for a maximum sample size of 30, this 
design will have a type I error rate () of 0.07 and 79% power.  The trial is stopped early 
for futility if the predictive probability of success is less than 0.1%.  The Bayesian prior 
used in determining the design was Beta (0.15, 0.85), a relatively non-informative prior 
with a mean response rate of 15%.  Under the null hypothesis, the expected sample size is 
24.0 subjects and probability of early termination is 84.5%. Under the alternative 
hypothesis, the expected sample size is 29.5 subjects and the probability of early 
termination is 12.2%.
5.1.3.
Arm C: GSK3052230 + Pemetrexed + Cisplatin
Starting with a cohort of 12 subjects and allowing for a maximum sample size of 30, this 
design will have a type I error rate (α) of 0.10 and 82% power.  The trial is stopped early 
for futility if the predictive probability of success is less than 0.1%.  The Bayesian prior 
used in determining the design was Beta (0. 5, 0.5), a relatively non-informative prior 
with a mean response rate of 50%.  Under the null hypothesis, the expected sample size is 
23.1 subjects and probability of early termination is 86.4%. Under the alternative 
hypothesis, the expected sample size is 29.5 subjects and the probability of early 
termination is 13.7%.
5.2.
Sample Size Sensitivity
No sample size sensitivity was performed.
5.3.
Sample Size Re-estimation
Sample size re-estimation is not planned for this study.
6.
ANALYSIS POPULATIONS
6.1.
All Treated Subjects
The All Treated Subjects (ATS) population will be comprised of all subjects who receive 
at least one dose of study treatment.
6.2.
All Evaluable Subjects Population
The study population used for decision-making at the interim analyses during the dose 
expansion cohorts of the study arms will be termed the All Evaluable Subjects
Population.  


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Since disease assessments are to be completed every 2 cycles during the first year of the 
study, we will set a cut-off date for inclusion in the All Evaluable Subjects Population of 
subject first dose approximately 42 days (2 cycles) prior to the date the data are extracted 
for the interim analysis.  In addition, those subjects who are ongoing and were enrolled 
prior to the cut-off date but have not had a disease assessment will not be included in the 
interim analysis (e.g. if they are late having their first scan or the scan data has not yet 
been received).  
6.3.
Pharmacokinetic Population
The Pharmacokinetic Population will consist of all subjects in the All Treated Subject 
Population for whom a blood sample for pharmacokinetics is obtained and analyzed.
6.4.
Pharmacodynamic Population
The Pharmacodynamic Population will consist of all subjects in the All Treated Subjects 
Population for whom a biomarker sample was obtained and analyzed.
6.5.
Assay Validation Population
The Assay Validation Population is defined as all subjects who were consented, screened 
for the study (regardless if the subject met eligibility requirements for study enrolment) 
and whose tissue was assayed by the central laboratory for FGFR1 amplification. Data 
from this population may be used for future validation of the assay.
6.6.
Analysis Datasets
The dataset used for summaries of response data during the dose expansion cohort 
interim analyses will be comprised of the All Evaluable Subjects Population.
The primary dataset for dose escalation cohort reviews, for review of safety data and 
listings of response data at interim analyses during the dose expansion cohort, and for the 
final analysis of efficacy and safety data will be the All Treated Subjects Population.
The primary dataset for the analysis of PK data will be comprised of the Pharmacokinetic 
Population.
The primary dataset for analysis of biomarker data, including potential 
predictive/prognostic biomarkers (DNA, RNA, or protein) of response in circulation 
and/or in tumor will be the Pharmacodynamic dataset.
The primary dataset for analysis of FGFR1 gene amplification data to support the IUO 
application and potential development of a companion diagnostic will be comprised of 
the Assay Validation Population.
7.
TREATMENT COMPARISONS
There will be no formal statistical comparison of dose groups. Comparisons of safety and 
PK data across dose groups will be made using descriptive statistics, separately for each 
Study Arm.


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For analysis of the overall response rate (ORR) for each study arm, ORR data from dose 
expansion cohorts are compared against historical control rates using the hypotheses 
specified in Section 2.4.  The type I error rate and power for this comparison is provided 
by study arm in Section 5.1.  
7.1.
Data Display Treatment and Other Subgroup Descriptors
The following treatment descriptor formats will be used on all applicable displays.  
Actual doses should be used in data displays.  An example is given for each study arm:
Study 
Arm
Description
Data Display Example
Order of Treatment 
Groups
A
GSK3052230 +  
Paclitaxel + Carboplatin
5 mg/kg GSK3052230 + 
200 mg/m2 Paclitaxel + 
AUC6 Carboplatin
Sort by dose of 
GSK3052230, then by 
dose of Paclitaxel, 
then by dose of 
Carboplatin
B
GSK3052230 + Docetaxel
5 mg/kg GSK3052230 + 
75 mg/m2 Docetaxel
Sort by dose of 
GSK3052230 then by 
dose of Docetaxel
C
GSK3052230 + 
Pemetrexed + Cisplatin
10 mg/kg GSK3052230 
+ 500mg/m2 Pemetrexed 
+ 75 mg/m2 Cisplatin
Sort by dose of 
GSK3052230, then by 
dose of Pemetrexed, 
then by dose of 
Cisplatin
Note: When there is not space for the entire title, the data display column header may 
read e.g. “Treatment (GSK3052230,Paclitaxel,Carboplatin)” and the dose description 
may be shortened to e.g. “5mg/kg,200mg/m2,AUC6”.
8.
GENERAL CONSIDERATIONS FOR DATA ANALYSES
Analysis datasets will be created according to GSK Integrated Data Standards Library 
(IDSL) for interim analyses and according to CDISC/ADaM standards for final reporting.  
Data will be listed and summarized according to GSK Integrated Data Standards Library 
(IDSL) reporting standards for both interim and final analyses. Formatting for dates, 
times, and decimal places will follow GSK standards except where specified.
The currently supported versions of SAS and Tibco Spotfire Clinical Graphics (TSCG)
software will be used to perform all data analyses, generate tables, figures, and listings.
All data in the database will be presented in by-subject data listings.
All data up to the time of study completion/withdrawal from study will be included in the 
analysis, regardless of duration of treatment.


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As the duration of treatment for a given subject will depend on efficacy and tolerability, 
the duration of follow-up will vary between subjects. There will be no imputation for 
missing data.
Unless otherwise stated, all listings will be sorted by study part, treatment group, center 
ID, subject number, cycle, cycle day, and then by visit date and time, if applicable.
Unless otherwise stated, continuous variables will be summarized with n, mean, median, 
standard deviation, minimum and maximum, and categorical variables will be 
summarized with frequency counts and percentages.
Data from Study Arms A-C will be reported separately.
Generally, summaries for each Study Arm will be produced by study treatment with 
pooling over the dose escalation and dose expansion portions of the Study Arm.  Certain 
displays may be created using only data from the dose escalation or dose expansion 
portion of the Study Arm or using only data from subjects who received the RP2D.
All laboratory data will be presented in GSK’s standard units for reporting.
”Worst-case post-baseline” values will be derived using scheduled and unscheduled 
visits.
Planned times relative to study drug dosing will be used in all tables and summary 
figures.
Generally, only pre-specified planned times will be used in the summaries, statistical 
analyses and calculations of any derived parameters and unscheduled readings will be 
listed. However, both unscheduled and scheduled readings will be included in the 
computation of maximum toxicity and in post-baseline shifts displays for labs and in any 
summary or listing of Potential Clinical Importance (PCI) values for vitals and ECG 
readings.
Actual, rather than planned, sampling times will be used in the derivation of PK 
parameters and in the individual concentration-time plots and listing of PK concentration 
data. Planned times will be used in the descriptive summaries and in mean and median 
plots. Concentration-time data will be listed according to actual sampling times relative 
to dosing time.
Assessment windows will not be defined for the purpose of classifying measurements 
obtained outside scheduled assessment times. 
Deviations from the analyses in the RAP will be identified in the CSR.
8.1.
Multicenter Studies
Data from all participating centers will be pooled prior to analysis. It is anticipated that 
subject accrual will be spread thinly across centers. Summaries of data by center will not, 
therefore, be provided. 


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8.2.
Other Strata and Covariates
In all efficacy analyses, there are no formal plans for any stratification. There are no 
formal plans for investigating any covariates.
8.3.
Examination of Subgroups
There are no formal plans for examining subgroups.
8.4.
Multiple Comparisons and Multiplicity
There will be no adjustment of Type I error rates for multiple comparisons.
9.
DATA HANDLING CONVENTIONS
9.1.
Premature Withdrawal and Missing Data
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 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 data. 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. 
In the event that the study is terminated, all available data will be listed and a review 
carried out by the study team to assess which statistical analyses are still considered 
appropriate.
Missing data occurs when any requested data is not provided, leading to blank fields on 
the collection instrument. These data will be indicated by the use of a “blank” in subject 
listing displays. Answers such as “Not applicable” and “Not evaluable” are not 
considered to be missing data and should be displayed as such.
Subjects with the designation of treatment relationship for adverse events (AE)s and 
serious adverse events (SAEs) missing will have the worst case assumed to impute the 
relationship: if relationship to study treatment is missing it will be assumed to be “Yes”. 
There will be no other imputation for missing data other than what is described in Section 
9.2 for partial dates and for missing exposure end dates.
9.2.
Derived and Transformed Data
The following sections provide a general description of the derived and transformed 
variables used to describe and analyze the data. Separate analysis dataset specifications 
provide full details on all data derivations and transformations including descriptions of 
core standard algorithms and standard Oncology algorithms. The analysis dataset 


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specifications will clearly communicate the content and source of the datasets supporting 
the statistical analyses.
9.2.1.
Reference dates
There are two reference dates:

The date of screening is the reference date for determination of age. This date is 
used as a reference for age because age is an eligibility requirement.

The treatment start date is the safety reference date as well as the efficacy 
reference date. The treatment start date is defined as the date of first dose of 
GSK3052230 study treatment.  It will be used to calculate study day for safety 
measures, to calculate study day for response measures, for calculation of 
treatment duration, and for baseline characteristic measures such as time since 
initial diagnosis.
9.2.2.
Study Day for Safety and Efficacy Measures
If the date of interest occurs on or after the safety reference date then the safety study day 
will be calculated as (date of interest - safety reference date) + 1. If the date of interest 
occurs before the safety reference date then the safety study day will be calculated as 
(date of interest – safety reference date). There is no safety study day 0.
9.2.3.
Duration and Elapsed Time
Durations (e.g., the duration of an adverse event, duration of exposure, etc.) are 
calculated as the stop date minus the start date plus one.
For elapsed time (e.g., the time since initial diagnosis):

If the reference date is on or after the event date, then the elapsed time is the 
reference date minus the event date + 1.

If the reference date is before the event date then the elapsed time is the reference 
date minus the event date.
When reporting time to event (TTE) durations such as PFS in months, divide the number 
of days by 30.4375; to report in weeks divide the number of days by 7; to report in years 
divide the number of days by 365.25. These algorithms for time to event return decimal 
numbers, and ignore the actual numbers of days in the months or years between start date 
and stop date. The "year" used in these algorithms is 365.25 days long, and the "month" 
is one twelfth of that year.
For converting all other durations (e.g., duration of adverse events, duration of exposure, 
age to weeks, months or years use the following:

To report the duration in weeks divide the number of days by 7.

To report the duration in months use:


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(YEAR(stopdate + 1) - YEAR(startdate)) * 12 + (MONTH(stopdate + 1) -
month(startdate) - 1) + (DAY(stopdate + 1) > = DAY(startdate))

To report the duration in years use:
intck('year', startdate, stopdate + 1) - (month(stopdate + 1) < month(startdate) or
(month(stopdate + 1) = month(startdate) and day(stopdate + 1) < day(startdate)))
The algorithms above for age and duration return whole numbers for months and years, 
accurately accounting for the actual numbers of days in the months or years between the 
start date and the stop date.
9.2.4.
Imputation of Partial Dates
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 overall survival analysis dataset.
With the exception of new anti-cancer start date on the Oncology time to event analysis 
dataset and exposure end date on the Exposure analysis dataset, imputed dates will also 
not be stored on datasets. 
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 
(see Section 9.3) or for specific analysis purposes as outlined below. 
The partial date imputation will follow ADaM conventions. The ADaM approach is to 
populate the numeric date variables with the imputed date and add a flag variable to the 
dataset that indicates the level of imputation. 
The flag variable can contain the values: blank, 'D', 'M', 'Y'. 
blank: indicates that no imputation was done
D='Day': indicates that the day portion of the date is imputed
M='Month': indicates that the month and day portions of the date are imputed
Y='Year': indicates that the entire date (year, month, and day) is imputed
Example of Date Variables: 
XYZD_ - character date variable
XYZDT - numeric date variable
XYZDTFL - flag variable
Details on imputing partial dates for specific datasets are outlined below.
Adverse Events (AE):
Imputations in the adverse events dataset are used for slotting events to the appropriate 
study time periods and for sorting in data listings.


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Dataset
Date
Missing 
Element
Rule
Adverse 
Events 
(AE)
Start 
Date
day, 
month, 
and year

No Imputation for completely missing dates
day, 
month

If study treatment start date is missing (i.e. subject did 
not start study treatment), then set start date = January 1.

Else if study treatment start date is not missing: 
o
If year of start date = year of study treatment start 
date then 

If stop date contains a full date and 
stop date is earlier than study 
treatment start date then set start date 
= January 1. 

Else set start date = study treatment 
start date. 
o
Else set start date = January 1.
day

If study treatment start date is missing (i.e. subject did 
not start study treatment), then set start date = 1st of 
month. 

Else if study treatment start date is not missing: 
o
If month and year of start date = month and year 
of study treatment start date then 

If stop date contains a full date and 
stop date is earlier than study 
treatment start date then set start 
date= 1st of month. 

Else set start date = study treatment 
start date.
o
Else set start date = 1st of month.
End 
Date

No imputation for partial end dates will be performed
Anti-Cancer Therapy and Radiotherapy:
Start and end dates are generally not imputed. If start or end dates need to be imputed for 
an analysis (e.g., to calculate duration), the rules for imputation will be defined within the 
algorithm of the derived covariate. Additionally, post treatment anti-cancer therapy and 
radiotherapy start dates may be imputed to determine date of new anti-cancer therapy. In 
this case only, the date of new anti-cancer therapy (not all anti-cancer therapy and 
radiotherapy start dates) will be stored on appropriate efficacy datasets. Imputed partial 
dates will not be used to derive time since most recent prior therapy. In addition, the 
cancer therapy treatment status variable, and not any variables that use imputed partial 
dates, will be used to differentiate prior and follow-up anti-cancer therapy and 
radiotherapy. 


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Dataset
Date
Missing 
Element
Rule
Anti-Cancer 
Therapy 
Radiotherapy 
Start 
Date
day, 
month, 
and year

No Imputation for completely missing dates
day, 
month

If partial date contains a year only set to January 
1st.
day

If partial date contains a month and year set to the 
1st of the month.
End 
Date

No imputation for partial end dates will be 
performed
Surgery:
The date of surgery or procedure is generally not imputed. If the date of surgery or 
procedure needs to be imputed for an analysis (e.g., to calculate duration or elapsed time 
as covariates for efficacy analyses), the rules for imputation will be defined within the 
algorithm of the derived covariate. Additionally, post treatment surgery or procedure
dates maybe imputed (where applicable) to determine date of new anti-cancer therapy. In 
this case only, the date of new anti-cancer therapy (not specific surgery or procedure
date) will be stored on appropriate efficacy datasets. The category for surgical procedure
variable, and not any variables that use imputed partial dates, will be used to differentiate 
prior, on, and follow-up surgical procedure data. The derived time in relation to treatment
variables are not needed for reporting of data because the category for surgical procedure 
variable can be used. Therefore, imputed dates are not needed for derivation of time in 
relation to treatment.
Dataset
Missing 
Element
Rule
Surgical 
Procedures
day, month, 
and year

No Imputation for completely missing dates
day, month

If partial date contains a year only set to January 
1st.
day

If partial date contains a month and year set to the 
1st of the month
Concomitant Medication and Blood and Blood Supportive Care Products:
Start and end dates may be imputed for use in derivation of the reference variables 
concomitant medication start and end relative to treatment and blood and blood 
supportive care start and end relative to treatment, but should not be permanently stored


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in the analysis datasets. The reference variables will be used to differentiate before, 
during and after for the concomitant medication or blood or blood supportive care start 
and end dates. The derived time in relation to treatment variables are not needed for 
reporting of these data.


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Dataset
Date
Missing 
Element
Rule
Concomitant 
Medication
Blood and 
Blood 
Supportive 
Care 
Products 
Start 
Date
day, 
month, 
and year

No Imputation for completely missing dates
day, 
month

If study treatment start date is missing (i.e. 
subject did not start study treatment), then set 
start date = January 1. 

Else if study treatment start date is not missing: 
o
If year of start date = year of study 
treatment start date then 

If stop date contains a full date and 
stop date is earlier than study 
treatment start date then set start 
date = January 1. 

Else set start date = study 
treatment start date. 
o
Else set start date = January 1.
day

If study treatment start date is missing (i.e. 
subject did not start study treatment), then set 
start date = 1st of month. 

Else if study treatment start date is not missing: 
o
If month and year of start date = month 
and year of study treatment start date then 

If stop date contains a full date and 
stop date is earlier than study 
treatment start date then set start 
date= 1st of month. 

Else set start date = study 
treatment start date.
o
Else set start date = 1st of month.
End 
Date
day, 
month, 
and year

No Imputation for completely missing dates
day, 
month

If partial end date contains year only, set end date 
= earliest of December 31 or date of last contact. 
day

If partial end date contains month and year, set 
end date = earliest of last day of the month or date 
of last contact (MSTONE.LCONTDT).


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Time to Event and Overall 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, or duration of 
response (i.e. start date for new anti-cancer therapy). Dates will only be imputed when a 
month and year are available but the day is missing. The imputed date(s) will not be 
stored on the anti-cancer therapy, radiotherapy, or surgical procedure datasets. The 
following rules will be used to impute the date when partial start dates are present on 
anti-cancer therapy radiotherapy, and/or surgical procedures datasets:
Dataset
Date
Missing 
Element
Rule
Anti-Cancer 
Therapy 
Where 
applicable: 
Radiotherapy 
Surgical 
Procedures
Start 
Date
day, month, 
and year

No Imputation for completely missing dates
day, month

No imputation for missing day and 
month (note the eCRF should only allow for 
missing day)
Day

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.
End 
Date

No imputation for partial end dates will be 
performed


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The date of new anti-cancer therapy is derived as the earliest date of new anti-cancer 
therapy (e.g., chemotherapy), radiotherapy (where applicable), or cancer related surgical 
procedure (where applicable) and will include imputed dates. If the date of new anti-
cancer therapy is an imputed date, then the date of new anti-cancer therapy flag variable 
is assigned the value of 'D' to indicate that the day portion of the date is imputed 
(following ADaM convention). 
As multiple dates are used to derive the date of new anti-cancer therapy, ensure that the 
date of new anti-cancer therapy flag is only set to ‘D’ if the derived date is imputed. For 
example, if the date of new radiotherapy is imputed but the date of new anti-cancer 
therapy is prior to date of new radiotherapy and the new anti-cancer therapy date is not a 
partial date then the flag should be set to missing as the date used for the new anti-cancer 
therapy is not an imputed date.
9.2.5.
Baseline Definition
Baseline will be defined as the most recent, non-missing value prior to or on the first 
study GSK3052230 treatment dose date. For laboratory data, baseline will be defined as 
the most recent, non-missing value from a central laboratory prior to or on the first study 
treatment dose date. If there are no central labs collected for a subject and lab test prior to 
or on the first dose of study treatment, the most recent, non-missing value from a local 
laboratory prior to or on the first dose of study treatment will be defined as the baseline 
value.
For subjects who did not receive GSK3052230 treatment during the study, baseline will 
be defined as the latest, non-missing collected value.
9.2.6.
Change from baseline
Change from baseline will be presented for safety data as described in Section 12.
Change from baseline is calculated as:

For records occurring after baseline: (visit value) – baseline value.
Percent change from baseline is calculated as:

For records occurring after baseline: ((change from baseline) / baseline value) * 100
If either the baseline or visit value is missing, the change from baseline and/or percent 
change from baseline is set to missing as well.
9.2.7.
Multiple Assessments
All data will be reported according to the nominal visit date for which it was reported 
(that is, no visit windows will be applied during dataset creation). Unscheduled data will
only be included in the display sections that report worst- case post-baseline. 
If multiple assessments are reported on the same date for the same scheduled planned 
time, then the mean of multiple measurements reported for the same date will be 


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analyzed, with the exception of laboratory data reported from both central and local 
laboratories. If laboratory data is reported from both central and local laboratories with 
the same date, then the central laboratory data will be analyzed to provide consistency 
with measurements from other subjects.  
Data from all assessments (scheduled and unscheduled), including multiple assessments, 
will be included in listings. 
9.2.8.
Actual Treatment
The subjects’ actual treatment will be derived from exposure data. If a subject’s actual 
treatment is the same as the assigned treatment, then actual treatment is the assigned 
treatment. If a subject receives a study treatment that is different from the assigned 
treatment for the entire time of treatment, then actual treatment is the different treatment 
(the treatment actually received).
9.2.9.
Treatment Cycle
In order to differentiate cycle variables based on the “assessment” cycle 
(timeslicing/eCRF collected) versus actual treatment cycle variables based on exposure
cycle start dates, treatment cycle, treatment cycle description, day with treatment cycle, 
day of start within treatment cycle, and day of end within treatment cycle, as appropriate, 
will be added to adverse events, ECG, laboratory, and vital sign analysis datasets.
Treatment cycle:

For non-planned visits/assessments select the cycle record for each subject where the 
dataset date variable is greater than or equal to cycle start date and less than or equal 
to cycle end date.

For planned visits/assessments where Day 1 assessments are assumed to be done 
prior to dosing, add 1 to the cycle start date and cycle end date from the cycle 
dataset. For each subject, select the cycle record where the dataset date variable is 
greater than or equal to the cycle start date and less than or equal to the cycle end 
date. 
Treatment cycle description:

Set treatment cycle description to the cycle dataset cycle description where the cycle 
dataset cycle is equal to the dataset treatment cycle.
Day within treatment cycle:

For each subject, dataset date variable minus the cycle start date from the cycle 
dataset + 1 where the dataset date variable is greater than or equal to the cycle 
dataset start date and less than or equal to the cycle end date and the cycle dataset 
cycle is equal to the dataset treatment cycle.
Day of start within treatment cycle:


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
For each subject, dataset start date variable minus the cycle start date from the cycle 
dataset + 1 where the dataset start date variable is greater than or equal to the cycle 
dataset start date and less than or equal to the cycle end date and the cycle dataset 
cycle is equal to the dataset treatment cycle.
Day of end within treatment cycle:

For each subject, dataset end date variable minus the cycle start date from the cycle 
dataset + 1 where the dataset end date variable is greater than or equal to the cycle 
dataset start date and less than or equal to the cycle end date and the cycle dataset 
cycle is equal to the dataset treatment cycle.
9.2.10.
Extended Loss to Follow-up or Extended Time without an 
Adequate Assessment
As the assessment schedule changes through the course of the protocol (i.e. every 2 
cycles for 1 year  then every 4 cycles thereafter), the following rules will be used for 
identifying extended loss to follow up or extended time without an adequate 
assessment(i.e. two or more missed assessments) .

If death or PD is on or prior to day 343 ( 16 cycles + 7 day window), then a 
subject will be identified as an extended loss to follow up if the subject did not 
have an adequate disease assessment during the time period of 91 days (4 cycles  
+ 7 day window) prior to death or PD; 

Else if death or PD is after day 343 (16 cycles + 7 day window) and on or prior to 
day 434 (16 cycles + 4 cycles + 14 day window), then a subject will be identified 
as an extended loss to follow up if the subject did not have an adequate disease 
assessment during the time period of 140 days (2 cycles+ 4 cycles  + 14 day 
window) prior to death or PD.

Else if death or PD is after day 434 ( 16 cycles + 4 cycles + 14 day window), then 
a subject will be identified as an extended loss to follow up if the subject did not 
have an adequate disease assessment during the time period of 182 days ( 8 cycles 
+ 14 day window) prior to death or PD.
9.2.11.
Date Associated with Response
For each disease assessment after baseline, determine a date associated with the response. 
For complete response (CR) and partial response (PR), assign to the latest date within the 
disease assessments. For stable disease (SD), Non-CR/Non-PD or Not Evaluable, assign 
to the earliest date within the disease assessments. For progressive disease (PD), assign to 
the earliest assessment date associated with the progression.
9.2.12.
Cardiac Scan Modalities (ECHO/MUGA)
The same modality (ECHO or MUGA) for determining cardiac scan data (e.g., left 
ventricular ejection fraction (LVEF)) should be used to follow a subject throughout the 
study. The absolute change from baseline values will not be calculated for any subjects


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where the post-baseline value was determined by a cardiac scan modality that is different 
than the one used to determine baseline value. 
9.2.13.
Derived and Transformed Variables
Progression-free survival
See Section 11 for details on analyses for progression-free survival, including censoring 
rules.
Pharmacokinetic Parameters
See Section 14 for details on the derivation of PK parameters.
For the purposes of calculating summary statistics and for statistical analysis, all PK 
parameters with the exception of tmax and %AUCex will be loge transformed.
Between-subject coefficient of variation (CVb%) will be calculated by the following 
methods, where SD is the standard deviation of the PK parameter data, calculated using 
either the raw data (untransformed) or the natural logarithm of the raw data 
(transformed).
Untransformed Data: 100 * (SD/Mean)
Transformed Data: 100 * (square root[exp(SD2)-1])
ECG Corrected QT Intervals 
An ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, 
and QTcF intervals will be used and these values will be input into the eCRF.  If only one 
of either QTcB or QTcF is available and it is necessary to derive the other corrected QT 
interval, the RR value preceding the measured QT interval should be back calculated 
from the collected QTc (either QTcF or QTcB) and used to compute the missing interval. 
If neither correction is available, do not calculate a corrected QTc value based on the 
collected RR, as the collected RR is the current RR interval rather than the RR interval 
preceeding the measured QT interval.
For reference, Fridericia’s formula is:
QT interval / ((RR interval/1000)^1/3), where RR interval is in msec 
For reference, Bazett’s formula is:
QT interval / ((RR interval/1000)^1/2), where RR interval is in msec


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9.3.
Study Time Periods
9.3.1.
Time in Relation to Treatment
Adverse events, serious adverse events, death, laboratory data, vitals, ECG, 
ECHO/MUGA, and questionnaire data (ECOG, LCSS), where appropriate, will be 
assigned to the study time periods defined below. Partial dates will be imputed into full 
dates, if applicable, for slotting data to the appropriate categories below (see Section 
9.2.4). 
Pre-therapy is defined as the time prior to the subject’s first dose of GSK3052230 
treatment. For AE, pre-therapy will be grouped into two subcategories:
a). Pre-therapy and Pre-chemo: the time prior to the subject’s first dose date of any study 
treatment.
b). Pre-therapy and On-chemo: the time after the first dose date of chemo treatment and 
prior to the first dose date of GSK3052230, for cases that the administration of chemo 
treatment prior to GSK3052230.
On-therapy is defined as the time from first dose of GSK3052230 treatment to the last 
dose date of GSK3052230 treatment plus 30 days. 
Post-therapy is defined as the time after the last dose date of GSK3052230 treatment 
plus 30 days. 
Some datasets include the first dose day as on-therapy and some exclude the first dose 
date as on-Therapy. The first dose day (Day 1) is considered pre-therapy for ECOG, 
ECG, vital signs, liver events, lab tests, and cardiac scan. The first dose day (Day 1) is 
considered to be on-therapy for adverse events and concomitant medications.
9.3.2.
Study Time Periods for Concomitant Medications 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 


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'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 
(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').
9.4.
Values of Potential Clinical Importance
9.4.1.
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.


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9.4.2.
ECG Parameters:
The following criteria will be used to flag electrocardiogram (ECG) values that are values 
of potential clinical importance: 
To identify QTc (Bazett’s or Fridericia’s) values of potential clinical importance, NCI-
CTCAE v4.0 will be used to assign grades (see adverse event ‘Electrocardiogram QT 
corrected interval prolonged’). Note that there is a slight inconsistency between CTCAE 
v4 and ICH E14 (Absolute QTc interval prolongation). It was decided to align with 
CTCAE for the oncology standard categories.
ECG Parameter
Potential Clinical Importance (PCI) Range
Unit
Absolute QTcF [QTcB] 
interval
450 to <481 (Grade 1)
481 to <501 (Grade 2)
501 (Grade 3)
Msec
Increase from baseline 
QTcF [QTcB]
Increase of 31 to 60
Increase of >60
Msec
The following criteria will be used to flag other ECG values that are values of potential 
clinical importance: 
ECG Parameter
Potential Clinical Importance (PCI) Range
Unit
PR interval
<110 (L) and >220 (H)
Msec
QRS interval
<75 (L) and >110 (H)
Msec
9.4.3.
Vital Signs
To identify heart rate values of potential clinical importance, NCI-CTCAE v4.0 will be 
used to assign categories that align with the grades for ‘Sinus bradycardia’, ‘Sinus 
tachycardia’, ‘Supraventricular tachycardia’, and ‘Ventricular tachycardia’.
The following criteria will be used to flag vital sign values that are values of potential 
clinical importance:
Vital Sign Parameter
Potential Clinical Importance (PCI) Range
Unit
Decrease from baseline 
Heart Rate
Decrease to <60
bpm
Increase from baseline 
Heart Rate
Increase to >100
bpm


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To identify blood pressure values of potential clinical importance, NCI-CTCAE v4.0 will 
be used to assign categories that align with the grades for ‘Hypertension’.
Vital Sign Parameter
Potential Clinical Importance (PCI) Range
Unit
Increase from baseline 
Systolic Blood Pressure
120 to <140 (Grade 1)
140 to <160 (Grade 2)
160 (Grade 3)
mmHg
Increase from baseline 
Diastolic Blood Pressure
80 to <90 (Grade 1)
90 to <100 (Grade 2)
100 (Grade 3)
mmHg
To identify temperature values of potential clinical importance, NCI-CTCAE v4.0 will be 
used to assign categories that align with the grades for ‘Hypothermia’ and ‘Fever’.
Vital Sign Parameter
Potential Clinical Importance (PCI) Range
Unit
Increase from baseline 
temperature
Increase to 38
Degrees 
C
Decrease from baseline 
Diastolic Blood Pressure
Decrease to 35
Degrees 
C
9.4.4.
Left Ventricular Ejection Fraction
The following criteria will be used to flag left ventricular ejection fraction (LVEF) values 
that are values of potential clinical importance: 
To identify LVEF values of potential clinical importance, NCI-CTCAE v4.0 will be used 
to assign categories that align with the grades for ‘Ejection fraction decreased’.
LVEF Parameter
Potential Clinical Importance (PCI) Range
Unit
Absolute change from 
baseline LVEF

No change or any increase

Any decrease
o
>0-<10 decrease
o
10-19 decrease
o
20 decrease
o
10 decrease and LLN
o
10 decrease and below LLN
o
20 decrease and LLN
o
20 decrease and below LLN
%
Relative change from 
baseline LVEF

20 decrease and LLN

20 decrease and below LLN
%


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10.
STUDY POPULATION
Unless otherwise stated, all tables and listings in this section will be based on the All 
Treated Subjects population, and all summaries and data listings will use treatment labels 
as specified in Section 7.
The list of displays for Study Population is shown in Section 20.1.1, Section 20.1.10 and 
Section 20.1.11 of the RAP. 
10.1.
Disposition of Subjects
A summary of the number of subjects in each of the analysis populations described in 
Section 6 will be provided. A listing of subjects excluded from analysis populations will 
also be provided.  The population for these two displays will be the All Screened Subjects 
Population.
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 listing of reasons for study 
withdrawal will also be provided.
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 reason for study treatment discontinuation. 
10.2.
Protocol Deviations
All protocol deviations will be summarized and listed and will include 
inclusion/exclusion deviations as well as other deviations. 
A separate summary and listing of inclusion/exclusion deviations will also be provided.
Additionally, a listing of planned and actual treatments will be provided.  This will show 
the actual treatment given for the subject’s first dose versus the planned treatment.
10.3.
Demographic and Baseline Characteristics
The demographic characteristics (e.g., age, race, ethnicity, sex, baseline height, 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. In addition, age will also be categorized and summarized by <18, 18-64, 65-
74, and >74. The count and percentage will be computed for sex and ethnicity.
Race and racial combinations will be summarized and listed.


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Separate summaries of demographic characteristics and race and racial combinations will 
be provided for the Screen Failure Population.
Disease history and characteristics at initial diagnosis and screening will be listed. 
Separate summaries of disease characteristics at initial diagnosis and screening will be 
provided. Medical conditions present at screening will be listed.
A summary of disease burden at baseline will be produced. Information on sites of 
metastatic disease at screening will be listed. 
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. The 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 radiotherapy will be listed. Prior cancer-related and non-cancer-related
surgeries will be listed. 
10.4.
Concomitant Medications
Concomitant medications will be coded using GSK Drug coding dictionary, summarized, 
and listed. The summary of concomitant medications will show the number and 
percentage of subjects taking concomitant medications by Ingredient. Multi-ingredient 
products will be summarized by their separate ingredients rather than as a combination of 
ingredients. Anatomical Therapeutic Chemical (ATC) classification Level 1 (Body 
System) information will be included in the dataset created but will not appear on the 
listing or summary.
In the summary of concomitant medications, each subject is counted once within each 
unique ingredient. For example, if a subject takes Amoxicillin on two separate occasions, 
the subject is counted only once under the ingredient “Amoxicillin”.
In the summary of concomitant medications, the ingredients will be summarized by the 
base only, using CMBASECD and CMBASE. 
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.
11.
EFFICACY
All efficacy analyses will be based on the All Treated Subjects population as defined in 
Section 6 unless otherwise specified. All analyses will be presented by study part and 
dose of study treatment.  Certain analyses, identified in the text below, will be produced  
only for subjects who received the RP2D for each Study Part.


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Efficacy assessments are based on RECIST 1.1 criteria for Parts A and B.  For Part C, 
both RECIST 1.1 and the modified RECIST criteria for MPM subjects will be used. In 
other words, MPM subjects will have tumor measurements for both criteria. 
For Part C, primary efficacy assessments will be based on the investigator-assessed 
modified RECIST criteria for MPM subjects.  Note that the modified RECIST criteria 
affect the way the tumors are measured, however the list of variables included in datasets 
and format of displays are unchanged from standard RECIST criteria.  
Overall Response Rate (ORR)
Overall Response Rate (ORR) is defined as the percentage of subjects achieving a 
confirmed CR or PR from the start of treatment until disease progression. This will be 
determined based on Investigator assessments of response.  The best overall response 
data will be summarized by dose of study treatment for each study part.  For Part C this 
display will be produced for both the RECIST and modified RECIST criteria.
Subjects with Not Evaluable (NE) or missing response will be treated as non-responders; 
i.e. they will be included in the denominator when calculating the percentage.
The 95% CI for response rates in each treatment arm will be calculated.
All data relating to response from the Investigator will be listed including lesion 
measurements, response assessments and best response.  Separate listings will be 
provided for RECIST and Modified RECIST criteria for Part C.
A waterfall plot of the Investigator-assessed percent change from baseline in tumor 
measurement at time of best response will be provided for each study part, separately for 
RECIST and Modified RECIST Criteria for Part C. The plot will be color-coded for best 
overall response. Indication of the subject number and dose will be provided below the 
plot.
Additionally, a bar chart of duration of treatment by subject with indications for treatment 
arm and investigator-assessed best response by RECIST criteria will be provided for each 
study part.  For Part C, the plot will display two investigator-assessed best responses; one 
for RECIST and the other for modified RECIST criteria.  
For Part C, a plot of FGF2 over expression level by best overall response from modified 
RECIST criteria will be produced.
Volumetric Analysis: Retrospective evaluation of tumor volumes will also be performed 
in subjects with sufficient CT or MRI imaging data. A listing and summary of tumor 
volumes by response and dose will be performed.
Brain and Bone Scans
Results from brain and bone scans will be listed.


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Forced vital capacity
FVC data will be listed and summarized.  Additionally, change from baseline FVC will 
be summarized.
Tumor Growth and Tumor Kinetics Analysis
A listing of information from prior tumor scans will be provided by Clinical Statistics.  
Tumor Growth and Tumor Kinetics Analysis will be the responsibility of Clinical 
Pharmacokinetics/Modelling & Simulation, GSK.  Outputs will be separate from the 
SAC package delivered by Clinical Programming (US).
Data from some arms of the study may be combined to describe the kinetics of tumor 
growth based on the sum of longest diameters and/or volume of target lesions, including 
information from prior tumor scans if the data warrant.  This analysis will be the 
responsibility of CPMS.
The kinetics of tumor growth may be described as a function of time using the NSCLC 
model described by the FDA [Wang, 2009]. The tumor size (TS) is expressed as:
TS(t) = BSL•e-SRt + PR•t
where TS(t) denotes the tumor size measured as the sum of longest distance (mm) of 
lesions or volume (mm3) at time t, BSL is the baseline tumor size, SR is the exponential 
tumor shrinkage rate constant and PR is the linear tumor progression rate.
The kinetics of tumor growth may also be described as a function of time using the model 
described by Claret [Claret, 2009]. The model is expressed as:
dTS(t)/dt = (KL-KD•e-t)•TS(t)
where TS(t) denotes the sum of longest distance (mm) of lesions or volume (mm3) at 
time t, with TS(0) being the baseline tumor size, KL represents the exponential tumor 
growth rate, KD represents the exponential rate of tumor shrinkage (i.e. drug effect on 
total tumor size), λ is the rate constant for drug resistance/disease progression.  A 
measure of exposure of one or more of the administered medications may be included in 
the models.
The equation proposed by Wang and/or Claret will be fit to the observed data using a 
mixed-effects model with NONMEM VII.  Other models of the kinetics of tumor growth, 
such as a 2-parameter model, may be used to analyze the data [Stein, 2011; Stein, 2012].
The time to tumor growth (TTG) may be estimated with parameters from the appropriate 
model. Subject characteristics such as baseline tumor size, performance status, LDH, age, 
sex, race, prior therapies, or radiotherapy, may be evaluated to determine which 
covariates have a significant effect on the kinetics of tumor growth.


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Progression-Free Survival
An analysis of progression-free survival (PFS) will be completed using RECIST criteria 
for Parts A and B and Modified RECIST criteria for Part C. Only subjects who received 
the RP2D will be included in summary displays for PFS although PFS will be calculated 
and listed for all subjects.  PFS is defined as the time from date of first dose of 
GSK3052230 to the date of first documented disease progression according to 
radiological or clinical assessment, or to date of death due to any cause.  For subjects who 
do not progress or die, PFS will be censored at the time of last radiological scan. Subjects 
who discontinue study with no post-treatment tumor assessment will be censored at date 
of first dose of study drug. 
A listing and summary of PFS will be produced for each study part.   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 Kaplan-Meier survival curve with 90% confidence bands will also be provided for 
each study part.  
Additionally, a shift summary comparing numerical categories of time to progression on 
last prior therapy to categories of progression-free survival on study may be produced if 
the data warrant.  
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 CR, 
PR, 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 9.2.10.
Subjects should not start subsequent anti-cancer therapy while on study.  However, if a 
subject received subsequent anti-cancer therapy while on study and prior to the date of 
documented events, PFS will be censored at the last adequate assessment (e.g., 
assessment where visit level response is CR, PR, or SD) prior to the initiation of therapy.
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 CR, PR, 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 the following table.


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Table 4
Assignments for Progression and Censoring Dates for PFS Analysis
Situation
Date of Event 
(Progression/Death) or 
Censoring 
Outcome
Event (Progression/Death)
Or Censored
No (or inadequate) baseline 
tumor assessments and the 
subject has not died (if the 
subject has died follow the
rules for death indicted at 
the bottom of the table)
Date of First Dose
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)
Date of First Dose
Censored
Progression documented 
between scheduled visits
Date of assessment of 
progression1
Event
No progression (or death) 
Date of last ‘adequate’ 
assessment of response2
Censored
New anticancer treatment 
started (prior to documented 
disease progression)3
Date of last ‘adequate’ 
assessment of response2 (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 
extended period without 
adequate assessments
Date of last ‘adequate’ 
assessment of response2
(prior to missed 
assessments)
Censored
1 The earliest of (i) Date of radiological assessment showing new lesion (if progression is based on new lesion); or (ii) 
Date of radiological assessment showing unequivocal progression in non target lesions, or (iii) Date of last 
radiological assessment of measured lesions (if progression is based on increase in sum of measured lesions); or 
(iv) Date of clinical assessment of progression


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2 An adequate assessment is defined as an assessment where the Investigator determined response is CR, PR, 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.
12.
SAFETY ANALYSES
Unless otherwise specified, all the safety analyses will be based on the All Treated
Subjects population as defined in Section 6 and summaries will include all events or 
assessments collected during the study. All the analyses will be performed by study part 
and treatment arm.
The list of displays for safety analyses are shown in Section 20.1.4, Section 20.1.5, 
Section 20.1.10 and Section 20.1.11 of the RAP. 
12.1.
Extent of Exposure
Extent of exposure to GSK3052230, Paclitaxel (Part A), Carboplatin (Part A), Docetaxel 
(Part B), Pemetrexed (Part C), and Cisplatin (Part C) will be summarized and listed 
separately.
For each component of study treatment, the number of cycles administered, dose intensity 
(dose delivered per cycle), and the cumulative dose received will be summarized with 
mean, median, standard deviation, minimum, and maximum. The number and percentage 
of subjects who received a given number of cycles (<4, 4-6, and >6 cycles) will be 
reported. The duration of exposure to study treatment in days (from first day to last day 
of treatment plus 1 day) will also be summarized. 
Dose reductions will be summarised by number of reductions and reasons for reductions. 
Dose escalations will be summarised by number of escalations and reasons for escalation. 
Missed doses will be summarised by number of missed doses and reasons for missed 
dose. Dose delays will be summarised by number of delays, reasons for the delays, and 
delay duration (days). The mean, standard deviation, median, minimum value, and 
maximum value will be computed for the duration of delay as well as the number and 
percentage of the delays ≤7, 8-14, 15-21 and >21 days. If for any reasons there are dose 
delays flagged in CRF but not confirmed by programmatic analysis, then ‘Duration of 
dose delays’ will be set to zero and these “delays” will be excluded for the calculation of 
mean, median and standard deviation of the duration of dose delays.
All the dose reductions, dose escalations, missed doses and dose delays will be listed 
separately.  Listings of incomplete infusions and infusion interruptions will also be 
provided.
A horizontal bar graph of duration of treatment in days (from first day to last day of 
treatment plus 1 day) will be produced.  This graph will display duration of treatment in 
days for each subject along with the treatment that the subject received and the subject’s 
best overall response.  


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12.2.
Adverse Events
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 modifications, SAEs, SAEs related to study treatment, fatal 
SAEs, and fatal SAEs related to study treatment will be produced.
The frequency and percentage of AEs 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. In the SOC row, the number of 
subjects with multiple events under the same system organ class will be counted once.A 
summary of all AEs will be provided by SOC with SOC’s displayed in descending order 
of total incidence by SOC and with AEs within each SOC in descending order of total 
incidence within the SOC.
The relationship between MedDRA SOC, PT, and Verbatim Text will be listed.
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.
Separate summaries will be provided for study treatment-related AEs in the same two 
ways as for overall AEs: 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. In the SOC 
row, the number of subjects with multiple events under the same system organ class will 
be counted once. A study treatment-related AE is defined as an AE for which the 
investigator classifies the relationship to study treatment as “Yes”. A worst case scenario 
approach will be taken to handle missing relatedness data, i.e. the summary table will 
include events with the relationship to study treatment as ‘Yes’ or missing. 
All AEs will be listed, including grade change details. For treatment-related AEs, the 
treatment to which the AE was related will be shown.  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.  A listing showing what DLT’s were recorded by cohort will also be 
provided.


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12.3.
Adverse Events of Special Interest
A comprehensive list of MedDRA terms based on clinical review will be used to identify 
each type of events. 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 special 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 
safety review team (SRT) agreements in place at the time of reporting.
The events of special interest included from protocol Section 1.6 (Summary of Risk 
Management). This section includes the following events:

Infusion-related reactions/Edema/Hypersensitivity

Anti-drug antibodies (would not be associated with specific AEs)

Anterior uveitis

Wound healing

Bowel perforation

Heart valve fibrosis

Peripheral Neuropathy

Hypothyroidism

Hematologic toxicity

Nephrotoxicity

Ototoxicity 
Summaries of the number and percentage of subjects with these events will be provided 
for each type of events separately. 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, the outcome of the event, maximum grade and the action taken for the 
event. The percentage will be calculated with the denominator as total number of 
subjects. The worst case approach will be applied at subject level for the event outcome 
and 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.
In addition, AEs of special interest will be listed separately.
Depending on the event, some additional analysis may be implemented (example: 
infusion and duration on study or response).


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12.4.
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 summarized based on the number 
and percentage of subjects. This summary will classify subjects by 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, fatal SAEs and study treatment-related fatal SAEs. The summary tables 
will be displayed in descending order of total incidence by PT only.
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.
12.5.
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 PT only and separate supportive listings will be generated with subject 
level details for those subjects:

AEs Leading to Discontinuation of Study Treatment 

AEs Leading to Dose Delays

AEs Leadings to Dose Reductions
12.6.
Pregnancies
While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be recorded 
as an AE or SAE as described in the protocol. If a subject or subject’s partner becomes
pregnant while on the study, the information will be included in the narratives and no 
separate table or listing will be produced.


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12.7.
Clinical Laboratory Evaluations
The assessment of laboratory toxicities will examine the following laboratory tests as 
specified in Table 5: 
Table 5
List of Clinical Laboratory Tests
Hematology
Platelet Count
Automated WBC Differential:
Red blood cell (RBC) Count
Neutrophils (absolute)
White blood cell (WBC) Count 
(absolute) 
Lymphocytes (absolute)
Hemoglobin
Monocytes (absolute)
Eosinophils (absolute)
Basophils (absolute)
Clinical Chemistry
Potassium, Sodium, Chloride, Total carbon dioxide, total Calcium, ionized calcium, magnesium, phosphate, 
albumin, glucose (fasting),
Blood urea nitrogen (BUN), Creatinine, Uric Acid, creatinine clearance
Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Gamma glutamyl transferase (GGT), 
Alkaline phosphatase, Total bilirubin (if elevated also test direct bilirubin) 
Thyroid hormone: TSH at Screening; every 2 cycles for the first year and then every 4 cycles. If TSH is 
positive, also test total T3, total T4, and free T4.
Pancreatic tests (amylase and lipase)
Coagulation tests (prothrombin time, partial thromboplastin time, international normalized ratio, and 
fibrinogen)
Routine Urinalysis
pH, glucose, protein, blood and ketones by dipstick
Microscopic examination (if blood or protein is abnormal)
Other screening tests
Pregnancy test for females (serum at screening, urine or serum post dose)
Laboratory grades will be reported using the Common Terminology Criteria for Adverse 
Events (CTCAE v4.0).  However, some tests are not graded using CTCAE.
For hematology, RBC is not gradable by CTCAE v4.0.
For clinical chemistry, BUN and creatinine clearance are not gradable by CTCAE v4.0. 
For sodium, potassium, calcium, glucose, and magnesium there will be two bi-directional 
parameters (hyper and hypo) created and the tests will be graded by CTCAE v4.0 in both 
directions.
For coagulation tests, INR and partial thromboplastin time are gradable by CTCAE v4.0 
but prothrombin time is not.
For thyroid function tests, neither the thyroid-stimulating hormone (TSH) test nor the free 
thyroxine (T4) test is gradable by CTCAE v4.0.


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Separate summary tables for hematology and chemical chemistry will be produced as 
detailed below.  Liver function, coagulation, thyroid and pancreatic laboratory tests will 
be included with chemical chemistry.
Summaries of lab data by maximum toxicity grade 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 labeled 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 post-baseline period, then the subject is counted in both the “Decrease to Low” 
categories and the “Increase to High” categories.
A supporting listing of all laboratory data will be provided. 
Detailed derivation of baseline assessment is specified in Section 9.2.5.
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.
Dipstick test results from urinalysis will be summarized at each scheduled visit. A 
supporting listing with subject level details will be provided.
12.7.1.
Analyses of Liver Function Tests
Summaries of hepatobiliary laboratory events including possible Hy’s law cases will be 
provided in addition to what has been described above. 
Possible Hy’s law cases are defined as any elevated (ALT≥3×ULN and total 
bilirubin≥2×ULN (with direct bilirubin 35% of total bilirubin, if direct bilirubin is 
measured)) OR (ALT ≥3×ULN and INR >1.5, if INR is measured).  Note that INR 
measurement is not required and the threshold value stated will not apply to patients 
receiving anticoagulants.
LFT patient profiles plots for subjects experiencing an ALT, AST or total bilirubin of 
toxicity grade 2 or above will be produced. 


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A plot of maximum total bilirubin versus maximum ALT will be generated. A trellis 
display of LFT shifts from baseline to maximum values will be provided. A matrix 
display of LFT results will also be produced.
12.8.
Other Safety Measures
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.
Vital Signs
Vital sign data will be listed.  Values of vital signs as well as the change from baseline 
will be summarized by scheduled visit using mean, median, standard deviation, minimum 
and maximum. 
In addition vital signs values will be categorized as follows:

Systolic BP (mmHg): Grade 0 (<120), Grade 1 (≥120-<140), Grade 2 (≥140-<160) 
and Grade 3 (≥160)

Diastolic BP (mmHg): Grade 0 (<80), Grade 1 (≥80-<90), Grade 2 (≥90-<100), and 
Grade 3 (≥100)

Heart rate (beats/min): <60, 60-100, and >100

Temperature (°C): <35, 35-38, ≥38
Summaries of increase in vital signs from the baseline with respect to the categories 
defined above will be performed. These summaries will display the number and 
percentage of subjects with any grade increase, increase to grade 2 and increase to grade 
3 at each scheduled assessment time and in the worst case post-baseline. 
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. 
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’s formula will be rounded to the integer and the 
values will be categorized into the following ranges: Grade 0 (<450), Grade 1 (450-480), 


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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 at each scheduled assessment time 
and in the worst case post-baseline.
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 at each 
scheduled assessment time and in the worst case post-baseline. Subjects with missing 
baseline values will be excluded from this summary.
The summaries for the QTc will use the collected value based on Fridericia’s formula.
In addition, ECG interval values will be also be summarized. 
Listings of abnormal ECG findings and a listing of ECG values will be provided.
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 (ECHO)
Absolute change from baseline in LVEF will be summarized at each scheduled 
assessment time and in the worst case post-baseline. 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:

Any increase

No change

Any decrease:
o 0 - <10% Decrease
o 10 -    <20% Decrease
o ≥20% Decrease

≥10% decrease and ≥LLN

≥10% decrease and < LLN

≥20% decrease and ≥LLN

≥20% decrease and < LLN
LVEF results will also be listed with subject level details including absolute change from 
baseline.


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Liver Events 
For any liver events that occur during the study, the liver event information for RUCUM 
score will be summarized, including whether the subject was age 55 or over, whether the 
subject became pregnant, liver imaging normal or not, a biopsy was taken or not, whether 
there was fasting or significant dietary change, whether the subject took any 
unconventional medications, timing when the event occurs (while on treatment or after 
stopping treatment) and summary statistics for time from first dose to start of liver event 
and time from last dose to start of liver event. If the number of events does not support a 
summary, then only listings will be produced.
For subjects with multiple events, the first event will be used for the summary tables. All 
events with subject level details will be displayed in a supporting listing.
Ocular Exams
Baseline ocular history and risk factors for cataracts will be summarized and listed.  
Summaries showing the number and percentage of normal and abnormal findings by 
scheduled visit and eye location (right or left) will be produced for external eye exam 
findings, indirect fundoscopic findings, and findings from the slit lamp exam excluding 
lens. Abnormal findings will be listed separately for each type of exam.
A categorical summary of the slit lamp examination using AREDS clinical lens opacity 
grading will be produced by scheduled visit and eye location.  
A summary of intraocular pressure and change from baseline intraocular pressure as 
measured by tonometry will be produced by scheduled visit and eye location.
A categorical summary of corrected visual acuity and a shift summary of corrected visual 
acuity will be produced by scheduled visit and eye location. 
All eye exam data will be listed, with separate listings for each type of eye examination.
Visual AEs will be summarized as describe in Section 12.2.
Immunogenicity
A listing of anti-GSK3052230 immunogenicity results will be produced. If any samples 
contain anti-GSK3052230 antibodies as determined by the ECL screening assay, they 
will be further characterized for specificity and antibody titers and these results will be 
included in the listing. 
A summary of anti-GSK3052230 immunogenicity results will show the number and 
percent of subjects with samples containing anti-GSK3052230 antibodies.
13.
HEALTH OUTCOMES ANALYSES
The Lung Cancer Symptom Scale (LCSS) for patients with lung cancer or LCSS-meso 
for MPM patients is self-administered by subjects (patient scales) and completed by the 


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investigator (observer scales) at screening, on day 1 of every cycle, and at the post-study 
visit. The LCSS consists of 9 patient-reported components and 6 observer-reported 
components. Using visual analogue scales (range from 0 to100), the patient scale 
measures the intensity of patient responses for appetite, fatigue, cough, hemoptysis, 
dyspnea, pain, and summary items overall symptomatic distress, interference with normal 
activities, and global quality of life. The observer items are scored categorically as None 
(100), Mild (75), Moderate (50), Marked (25), and Severe (0).  The observer items are 
loss of appetite, fatigue, cough, hemoptysis, dyspnea, and pain.  The LCSS-meso 
questionnaire has 8 patient-reported components and 5 observer-reported components as 
hemoptysis is not included.
All collected data for LCSS (Parts A and B) and LCSS-Meso (Part C) will be listed.    
A summary of LCSS (or LCSS-Meso) patient component scores and a summary of 
observer-assessed component scores will be provided.  These summaries will be provided 
by scheduled visit.  In addition, a summary of LCSS (or LCSS-Meso) change from 
baseline patient scores for patient component scores will be provided.  The change from 
baseline summary will be produced by visit and will also include a “best case post-
baseline” row.  Shift summaries for observer-assessed scores will be produced for each 
component by scheduled visit and will include a best case post-baseline row.
A summary of the number of patients with improvement in 2 observer-assessed scores 
at any one time point will be produced.  Similarly, a categorical summary of the number 
and percentage of patients achieving at least a 10mm improvement in at least one patient-
assessed component at any time point will be provided.  
Spaghetti plots of patient-assessed components will be provided for each component, 
with data from observers overlaid.  Median plots over time will also be provided for each 
component for both patient-assessed and observer components.
If the data warrant, the relationship between best overall response by RECIST (modified 
RECIST for MPM) and LCSS (LCSS-Meso for MPM) assessments may be explored. 
Plots of patient-assessed component best change from baseline by category of best 
overall response may be produced for components of particular interest.  In addition, a 
contingency table showing the number and percentage of patients achieving improvement 
in 2 observer-assessed scores at any one time point by category of best overall response 
may be provided.
If the data warrant, comparisons of patient-assessed and observer-assessed components 
may be made.  Graphs of best case change from baseline in patient-assessed scores by 
best case change from baseline in observer-assessed scores may be created for 
components of particular interest.
If warranted, mixed-effects models may be used to model subject data over time for 
patient-assessed components of particular interest.  Independent variables may include 
the baseline component score and time as fixed effects and subject as a random effect.


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14.
PHARMACOKINETIC ANALYSES
The reconciliation of the PK Case Report Form (CRF) and SMS2000 data will be 
performed by, or under the direct auspices of, Data Sciences - Oncology, 
GlaxoSmithKline.
The merge of PK concentration data and CRF data to generate a dataset with actual blood 
sampling times, actual time relative to dosing, and PK concentrations as well as the 
listings and summaries of concentration data will be performed after DBF by, or under 
the direct auspices of, Clinical Programming (US), GlaxoSmithKline.
Population PK analyses will be the responsibility of Clinical Pharmacokinetics/Modelling 
& Simulation, GSK.
Derivation of pharmacokinetic parameters for subjects with extensive PK sampling only, 
will be performed by, or under the direct auspices of, Clinical Pharmacology Modeling
and Simulation (CPMS), GlaxoSmithKline.
Statistical analysis of the pharmacokinetic parameters for subjects undergoing extensive 
PK sampling will be performed by, or under the direct auspices of, Clinical Statistics 
(US), GlaxoSmithKline.
Unless otherwise stated, all tables, figures and listings in this section will be based on the 
Pharmacokinetic Population, and all summaries, figures and data listings will use 
treatment labels specified in Section 7.1.
The list of displays for PK is shown in Section 20.1.6, Section 20.1.7 and Section 20.1.10
of the RAP.
14.1.
Drug Concentration Measures
Concentrations of GSK3052230, Paclitaxel, Docetaxel, and Pemetrexed in plasma will be 
listed and summarized by study part, treatment group and nominal time. Standard 
summary statistics will be calculated (i.e. mean, standard deviation, median, minimum 
and maximum). Refer to the PK Guidance document GUI_51487, “Non-Compartmental 
Analysis of Pharmacokinetic Data”, for more information regarding the handling of 
plasma concentrations below the assay’s lower limit of quantification (NQ).  For the 
subset of subjects who undergo extensive PK sampling for GSK3052230, individual, 
mean, and median concentration plots will be produced for the extensive sampling days, 
with the profile for Cycle 1 Day 1 through the pre-infusion concentration for Cycle 2 Day 
1 included (i.e., x-axis ends at Cycle 2 Day 1 timepoint). Separate individual, mean, and 
median concentration plots will focus on Cycle 1 Day 1 through the first 24-hour period 
only. For the subset of subjects who undergo extensive PK sampling for Paclitaxel,
Docetaxel, and Pemetrexed, individual, mean, and median concentration plots will be 
produced for the extensive sampling day, with the profile for Cycle 2 Day 1 (i.e., x-axis 
ends at Cycle 2 Day 1 12 hours).
Box and whisker plots showing pre-infusion concentration data vs. Study Arm will be 
separately provided for Cycle 1 Day 8, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 6 Day 1 and 


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Cycle 12 Day 1.  Similar plots will be created for the concentrations at the end of 
GSK3052230 infusion on those days.
14.2.
Deriving and Summarizing Pharmacokinetic Parameters
For subjects in Arms A, B, and C who undergo extensive PK sampling, the following 
pharmacokinetic parameters will be determined from the plasma concentration-time data 
for GSK3052230. The pharmacokinetic parameters will be calculated by standard non-
compartmental analysis according to current working practices and using WinNonlin 
Professional, version 3.0 or higher. All calculations of non-compartmental parameters 
will be based on actual sampling times.
1.
The first occurrence of the maximum observed plasma concentration determined 
directly from the raw concentration-time data (Cmax).
2.
The time at which Cmax is observed will be determined directly from the raw 
concentration-time data (tmax).
PK parameters of GSK3052230 will be listed and summarized separately for Arms A, B, 
and C, and by dose for subjects in the extensive PK sampling group only.  All derived PK 
parameters will be listed. For Cmax the following summary statistics will be calculated 
for each study part, dose, and study day for which PK parameters were calculated: 
median, minimum, maximum, arithmetic mean, 95% confidence interval for the 
arithmetic mean, standard deviation, coefficient of variation, geometric mean, 95% 
confidence interval for the geometric mean and standard deviation of logarithmically 
transformed data. For tmax, median, maximum, minimum, arithmetic mean, 95% 
confidence interval, and standard deviation will be calculated. All PK parameters will be 
reported to at least 3 significant digits, but to no more significant digits than the precision 
of the original data.
14.3.
Population Pharmacokinetic Analyses
Population PK analysis will be the responsibility of Clinical Pharmacokinetics/Modelling 
& Simulation, GSK.  Plasma GSK3052230 concentration-time from patients with 
extensive and limited sampling may be combined with data from other studies and will be 
analyzed using a population pharmacokinetic approach.  A nonlinear mixed effects model 
will be used to determine population pharmacokinetic parameters (clearances, CL and 
volumes of distribution, V) and identify important covariates (e.g., age, weight, or disease 
related covariates).  Summary exposure measures (Cmax, AUC and average 
concentration Cav defined as time corrected AUC [AUC/]) will also be computed. 
Results of this analysis may be provided in a separate report.
15.
PHARMACOKINETIC/PHARMACODYNAMIC ANALYSES
PK/PD analyses will be the responsibility of Clinical Pharmacokinetics/Modelling & 
Simulation, GSK.  Outputs generated from this analysis will be separate from outputs 
produced by Clinical Programming (US). Observed or predicted concentrations or 
summary exposure measure (eg; Cmax, Ctrough, and Cav) may be combined with safety 


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and efficacy pharmacodynamic measures of interest to examine potential exposure 
response relationships.  Graphical evaluation will first be performed. 
Where evidence of activity is seen, linear and/or non-linear mixed effect models may be 
fitted to the data to estimate PK/PD parameters of interest (e.g. slope, baseline (E0), 
concentration for 50% of maximum effect (EC50) and maximum effect (Emax)).
If needed for analysis, a PK/PD analysis data set will be generated by Clinical 
Programming (US). 
16.
IMMUNOGENECITY ANALYSES
For the immunogenicity assessment, serum will be tested for the presence of anti-
GSK3052230 antibodies using one type of antibody assays, i.e. a binding assay. For the 
binding assay, there will be 3-steps testing schema: screening, confirmation and titration 
steps.  A screening assessment is performed which produces a result of positive or 
negative. For samples with a positive screening result, a confirmatory assay is then 
carried out, which also produces a result of positive or negative. For samples with a 
positive confirmation result, a titer value will also be obtained to quantify the degree of 
binding in the titration assay step. Patients will be viewed as positive for the binding 
assay if the confirmatory assay was positive.
For the incidence of patients with positive binding antibody, a table will be produced 
summarizing results for the binding antibody assay by treatment group and visit. The 
table will include the number and proportion of subjects in each result category for each 
visit (including early withdrawal visit). Binding confirmatory assay results will be 
categorized as negative, transient positive (defined as a single positive immunogenic 
response that does not occur at the final assessment) or persistent positive (defined as a 
positive immunogenic response at least 2 consecutive assessments or a single result at the 
final assessment).  A separate table will be produced summarizing the confirmatory assay 
results by treatment group and visit.  
For the titer value, a table will be produced to summarize the median, min and max titer 
values among all visits by treatment group. This table will also summarize the median, 
min and max of the highest titer values from each subject.
17.
TRANSLATIONAL RESEARCH
17.1.
FGF Biomarkers Analyses
In Arms A and B, a requirement for inclusion is evidence of FGFR1 gene amplification 
in tumor tissue as determined by a central laboratory (CLIA or appropriate certification) 
using a laboratory developed test.
In Arm C, FGF2 expression will be evaluated retrospectively by IHC to determine if 
expression levels of FGF2 are associated with response to GSK3052230.
Any remaining tissue from this study may be used for:


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
Development and validation of a potential IUO assay and companion diagnostic test, 
e.g., FGFR1 gene amplification by FISH or FGF2 expression by IHC.

Alternative biomarkers of FGF pathway signalling. 

Biomarker research (protein, RNA and DNA) including status of RTK/PI3K/AKT 
pathways and cancer development and additional testing of DNA, RNA, or protein 
biomarkers related to the function of GSK3052230 if ongoing research identifies or
defines additional predictive and prognostic biomarkers
Exploratory analysis may be performed to examine potential relationships between 
anticancer activity and changes in markers of deregulation of FGF signaling pathway 
(example: FGFR1 gene amplification) or tumor biology (e.g. cytokines, acute phase 
proteins, relevant transcripts and/or proteins) or between anticancer activity and potential 
markers of sensitivity.
The results of translational research investigations may be reported separately from the 
main clinical study report or as an amendment.  All endpoints of interest from all 
comparisons will be descriptively and/or graphically summarized as appropriate to the 
data.
17.1.1.
FGFR1 Gene Amplification Assay
For Arm A and B, a fluorescence in situ hybridization (FISH) -based FGFR1 assay will be 
performed for the detection of abnormalities in tissue samples. FGFR1 assay will be 
performed one time on tissue samples from each subject. For each of Arm A, Arm B and 
Arm A+B, two summary tables will be produced to summarize the FGFR1 assay results. 

A table to summarize n, mean, median, standard deviation, minimum and 
maximum of the following FGFR1 quantitative results of all treated subjects 
across all treatment dose levels.
-
FGFR1/CEP Ratio
-
Average FGFR1 Signals per Cell
-
Average CEP 8 signals per Cell
-
Percentage of tumor nuclei containing ≥5 FGFR1 signals

A table to summarize frequency of amplified samples, amplification rates (in 
percentage) out of interpretable samples, and overall amplification rates (in 
percentage) out of all samples including interpretable and non-interpretable 
samples.
Scatterplots will be produced to show the correlation among the following FGFR1 
quantitative results which used for establishing gene amplification criteria.

FGFR1/CEP Ratio vs. Average FGFR1 Signals per Cell 

FGFR1/CEP Ratio vs. Percentage of tumor nuclei containing ≥5 FGFR1 signals 

Average FGFR1 Signals per Cell vs. Percentage of tumor nuclei containing ≥5 
FGFR1 signals


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In addition, plots of FGFR1 quantitative results by best response (in terms of RECIST 1.1 
criteria), FGFR1 quantitative results vs. duration of treatment, and FGFR1 quantitative 
results vs. PFS will be produced.
17.1.2.
FGF2 Immunohistochemistry Assay
For Arm C, the FGF2 immunohistochemistry assay will be performed to specifically 
detect the expression of the FGF2 in human mesothelium tissue. For each subject 
enrolled in Arm C, the FGF2 assay will be performed once on tissue samples. Nuclear 
staining and cytoplasm staining are to be scored using qualitative scoring criteria (0= no 
staining, 1+ = weak staining, 2+ = moderate staining, 3+ = strong staining), along with an 
estimation of the percentage of cell type demonstrating that staining pattern. The H-score 
is then determined based on the staining scores using the following formula: 
     H-score = (Percentage of no staining × 0) + (Percentage of weak staining × 1) 
                     + (Percentage of moderate staining × 2) + (Percentage of strong scoring × 3)
A listing to display the H-score of cytoplasma staining, H-score of nuclear staining, best 
responses (in terms of RECIST 1.1 criteria), duration of treatment and PFS for each 
subject will be produced. 
Plots of H-scores by best response, H-score vs. duration of treatment, and H-score vs. 
PFS will be produced.


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18.
PHARMACOGENETICS
A listing of sample accountability will be provided, showing which subjects gave 
samples for PGx analysis.  PGx analysis, if done, will be the subject of a separate PGx 
RAP.


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19.
REFERENCES
Brookmeyer R, Crowley J. A confidence interval for the median survival time. 
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Claret L., Girard P., Hoff PM, et al. Model-based prediction of Phase III overall survival 
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GUI_114801: Guidance on the Content and Format of Clinical Summary Document 
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GUI_137354: Information for Authors: Reporting and Analysis Plans
GUI_51349: Information for Authors: Clinical Pharmacology Reporting and Analysis 
Plan
Hanna N, Shepherd FA, Fossella FV, et al. Randomized Phase III trial of pemetrexed 
versus docetaxel in patients with non-small cell lung cancer previously treated with 
chemotherapy. J Clin Oncol 2004; 22(9):1589-1597.
Lee J Jack, Liu Diane D. A predictive probability design for phase II cancer clinical 
trials. Clinical Trials. 2008; 5(2):93-106.
Socinski MA, Bondarenko I, Karaseva NA, et al. Weekly nab-paclitaxel in combination 
with carboplatin versus solvent based paclitaxel plus carboplatin as first-line therapy in 
patients with advanced non-small cell lung cancer: Final results of a Phase III trial. J Clin 
Oncol 2012; 30:2055-2062.
SOP_130050: Managing Protocol Deviations
SOP_54838: Development, Review and Approval of Reporting and Analysis Plans
SOP_54839: Development of Summary Document Analysis Plans
Stein WD, Gulley JL, Schlorn J, et al. Tumor regression and growth rates determined in 
five intramural NCI prostate cancer trials: the growth rate constant as an indicator of 
therapeutic efficacy. Clin Cancer Res 2011; 17:907-917.
Stein WD, Wilkerson J, Kim ST, et al. Analyzing the pivotal trial that compared sunitinib 
and INF-α in renal cell carcinoma, using a method that assesses tumor regression and 
growth. Clin Cancer Res. 2012; 18:2374-2381.
Vogelzang NJ, Rusthoven JJ, Symanowski J, et al., Phase III study of pemetrexed in 
combination with cisplatin versus cisplatin alone in patients with malignant pleural 
mesothelioma. J Clin Oncol. 2003; 21(14): 2636-44.
Wang Y, Sung C, Dartois C, et al. Elucidation of relationship between tumor size and 
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development. Clin Pharmacol Therap 2009; 86: 167-174.


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20.
APPENDICES
20.1.
Appendix 1: Data Displays
20.1.1.
Study Population Tables
Table No.
Title
Population 
1.0010
Summary of Study Populations, Arm A
All Screened Subjects
1.0020
Summary of Study Populations, Arm B
All Screened Subjects
1.0030
Summary of Study Populations, Arm C
All Screened Subjects
1.1110
Summary of Subject Disposition, Arm A
All Treated Subjects
1.1120
Summary of Subject Disposition, Arm B
All Treated Subjects
1.1130
Summary of Subject Disposition, Arm C
All Treated Subjects
1.1210
Summary of Study Treatment Status, Arm A
All Treated Subjects
1.1220
Summary of Study Treatment Status, Arm B
All Treated Subjects
1.1230
Summary of Study Treatment Status, Arm C
All Treated Subjects
1.1310
Summary of Inclusion/Exclusion Criteria Deviations, Arm A
All Treated Subjects
1.1320
Summary of Inclusion/Exclusion Criteria Deviations, Arm B
All Treated Subjects
1.1330
Summary of Inclusion/Exclusion Criteria Deviations, Arm C
All Treated Subjects
1.1410
Summary of Protocol Deviations, Arm A
All Treated Subjects
1.1420
Summary of Protocol Deviations, Arm B
All Treated Subjects
1.1430
Summary of Protocol Deviations, Arm C
All Treated Subjects
1.2010
Summary of Demographic Characteristics, Arm A
All Treated Subjects
1.2020
Summary of Demographic Characteristics, Arm B
All Treated Subjects
1.2030
Summary of Demographic Characteristics, Arm C
All Treated Subjects
1.2040
Summary of Demographic Characteristics for Screen Failure 
Population, Arm A
Assay Validation
1.2050
Summary of Demographic Characteristics for Screen Failure 
Population, Arm B
Assay Validation
1.2060
Summary of Race and Racial Combination Details, Arm A
All Treated Subjects
1.2070
Summary of Race and Racial Combination Details, Arm B
All Treated Subjects
1.2080
Summary of Race and Racial Combination Details, Arm C
All Treated Subjects
1.2090
Summary of Race and Racial Combination Details for Screen 
Failure Population, Arm A
Assay Validation
1.2091
Summary of Race and Racial Combination Details for Screen 
Failure Population, Arm B
Assay Validation
1.2110
Summary of Disease Burden at Baseline, Arm A
All Treated Subjects
1.2120
Summary of Disease Burden at Baseline, Arm B
All Treated Subjects
1.2130
Summary of Disease Burden at Baseline, Arm C
All Treated Subjects
1.2140
Summary of Substance Use, Arm A
All Treated Subjects
1.2150
Summary of Substance Use, Arm B
All Treated Subjects
1.2160
Summary of Substance Use, Arm C
All Treated Subjects
1.3210
Summary of Disease Characteristics at Initial Diagnosis, Arm A
All Treated Subjects
1.3220
Summary of Disease Characteristics at Initial Diagnosis, Arm B
All Treated Subjects


CONFIDENTIAL
FGF117360
62
Table No.
Title
Population 
1.3230
Summary of Disease Characteristics at Initial Diagnosis, Arm C
All Treated Subjects
1.3240
Summary of Disease Characteristics at Screening, Arm A
All Treated Subjects
1.3250
Summary of Disease Characteristics at Screening, Arm B
All Treated Subjects
1.3260
Summary of Disease Characteristics at Screening, Arm C
All Treated Subjects
1.4010
Summary of Prior Anti-Cancer Therapy, Arm B
All Treated Subjects
1.4020
Summary of Prior Anti-Cancer Therapy, Arm C
All Treated Subjects
1.4030
Summary of Prior Dictionary Coded Anti-Cancer Therapy, Arm B
All Treated Subjects
1.4040
Summary of Prior Dictionary Coded Anti-Cancer Therapy, Arm C
All Treated Subjects
1.4050
Summary of Number of Prior Anti-Cancer Therapy Regimens, 
Arm B
All Treated Subjects
1.4060
Summary of Number of Prior Anti-Cancer Therapy Regimens, 
Arm C
All Treated Subjects
1.4070
Summary of Best Response to Most Recent Prior Anti-Cancer 
Therapy, Arm B
All Treated Subjects
1.4080
Summary of Best Response to Most Recent Prior Anti-Cancer 
Therapy, Arm C
All Treated Subjects
1.5010
Summary of Concomitant Medications by Ingredient, Arm A
All Treated Subjects
1.5020
Summary of Concomitant Medications by Ingredient, Arm B
All Treated Subjects
1.5030
Summary of Concomitant Medications by Ingredient, Arm C
All Treated Subjects
1.5040
Summary of Blood Products after Start of Study Medication, Arm 
A
All Treated Subjects
1.5050
Summary of Blood Products after Start of Study Medication, Arm 
B
All Treated Subjects
1.5060
Summary of Blood Products after Start of Study Medication, Arm 
C
All Treated Subjects
1.5070
Summary of Blood Supportive Care Products after the Start of 
Study Medication, Arm A
All Treated Subjects
1.5080
Summary of Blood Supportive Care Products after the Start of 
Study Medication, Arm B
All Treated Subjects
1.5090
Summary of Blood Supportive Care Products after the Start of 
Study Medication, Arm C
All Treated Subjects
20.1.2.
Efficacy Tables
No.
Title
Population 
2.0010
Summary of Investigator-Assessed Best Response with 
Confirmation (RECIST 1.1 Criteria), Arm A
All Treated Subjects
2.0020
Summary of Investigator-Assessed Best Response with 
Confirmation (RECIST 1.1 Criteria), Arm B
All Treated Subjects
2.0030
Summary of Investigator-Assessed Best Response with 
Confirmation (RECIST 1.1 Criteria), Arm C
All Treated Subjects
2.0040
Summary of Investigator-Assessed Best Response without 
Confirmation (RECIST 1.1 Criteria), Arm A
All Treated Subjects
2.0050
Summary of Investigator-Assessed Best Response without 
Confirmation (RECIST 1.1 Criteria), Arm B
All Treated Subjects


CONFIDENTIAL
FGF117360
63
No.
Title
Population 
2.0060
Summary of Investigator-Assessed Best Response without 
Confirmation (RECIST 1.1 Criteria), Arm C
All Treated Subjects
2.0070
Summary of Investigator-Assessed Best Response with 
Confirmation (Modified RECIST Criteria), Arm C
All Treated Subjects
2.0080
Summary of Investigator-Assessed Best Response without 
Confirmation (Modified RECIST Criteria), Arm C
All Treated Subjects
2.1010
Summary of Kaplan-Meier Estimates of Investigator-Assessed 
Progression-Free Survival, Arm A
All Treated Subjects
2.1020
Summary of Kaplan-Meier Estimates of Investigator-Assessed 
Progression-Free Survival, Arm B
All Treated Subjects
2.1030
Summary of Kaplan-Meier Estimates of Investigator-Assessed 
Progression-Free Survival, Arm C
All Treated Subjects
20.1.3.
Efficacy Figures
No.
Title
Population 
12.0010
Investigator-Assessed Percent Change at Maximum Reduction 
from Baseline in Tumor Measurement (RECIST 1.1 Criteria), Arm 
A
All Treated Subjects
12.0020
Investigator-Assessed Percent Change at Maximum Reduction 
from Baseline in Tumor Measurement (RECIST 1.1 Criteria), Arm 
B
All Treated Subjects
12.0030
Investigator-Assessed Percent Change at Maximum Reduction 
from Baseline in Tumor Measurement (RECIST 1.1 Criteria), Arm 
C
All Treated Subjects
12.0040
Investigator-Assessed Percent Change at Maximum Reduction 
from Baseline in Tumor Measurement (Modified RECIST Criteria), 
Arm C
All Treated Subjects
12.0050
Graph of Kaplan Meier Investigator-Assessed Progression-Free 
Survival Curve with 95% Confidence Band at the Recommended 
Phase 2 Dose, Arm A
All Treated Subjects
12.0060
Graph of Kaplan Meier Investigator-Assessed Progression-Free 
Survival Curve with 95% Confidence Band at the Recommended 
Phase 2 Dose, Arm B
All Treated Subjects
12.0070
Graph of Kaplan Meier Investigator-Assessed Progression-Free 
Survival Curve with 95% Confidence Band at the Recommended 
Phase 2 Dose, Arm C
All Treated Subjects
20.1.4.
Safety Tables
No.
Title
Population 
3.0010
Summary of Exposure to GSK3052230, Arm A
All Treated Subjects
3.0020
Summary of Exposure to GSK3052230, Arm B
All Treated Subjects
3.0030
Summary of Exposure to GSK3052230, Arm C
All Treated Subjects
3.0040
Summary of Exposure to Paclitaxel, Arm A
All Treated Subjects
3.0050
Summary of Exposure to Carboplatin, Arm A
All Treated Subjects
3.0060
Summary of Exposure to Docetaxel, Arm B
All Treated Subjects


CONFIDENTIAL
FGF117360
64
No.
Title
Population 
3.0070
Summary of Exposure to Pemetrexed, Arm C
All Treated Subjects
3.0080
Summary of Exposure to Cisplatin, Arm C
All Treated Subjects
3.0090
Summary of Dose Reductions of GSK3052230, Arm A
All Treated Subjects
3.0100
Summary of Dose Reductions of GSK3052230, Arm B
All Treated Subjects
3.0110
Summary of Dose Reductions of GSK3052230, Arm C
All Treated Subjects
3.0120
Summary of Dose Reductions of Paclitaxel, Arm A
All Treated Subjects
3.0130
Summary of Dose Reductions of Carboplatin, Arm A
All Treated Subjects
3.0140
Summary of Dose Reductions of Docetaxel, Arm B
All Treated Subjects
3.0150
Summary of Dose Reductions of Pemetrexed, Arm C
All Treated Subjects
3.0160
Summary of Dose Reductions of Cisplatin, Arm C
All Treated Subjects
3.0170
Summary of Dose Delays of GSK3052230, Arm A
All Treated Subjects
3.0180
Summary of Dose Delays of GSK3052230, Arm B
All Treated Subjects
3.0190
Summary of Dose Delays of GSK3052230, Arm C
All Treated Subjects
3.0200
Summary of Dose Delays of Paclitaxel, Arm A
All Treated Subjects
3.0210
Summary of Dose Delays of Carboplatin, Arm A
All Treated Subjects
3.0220
Summary of Dose Delays of Docetaxel, Arm B
All Treated Subjects
3.0230
Summary of Dose Delays of Pemetrexed, Arm C
All Treated Subjects
3.0240
Summary of Dose Delays of Cisplatin, Arm C
All Treated Subjects
3.0250
Summary of Missed Doses of GSK3052230, Arm A
All Treated Subjects
3.0260
Summary of Missed Doses of GSK3052230, Arm B
All Treated Subjects
3.0270
Summary of Missed Doses of GSK3052230, Arm C
All Treated Subjects
3.0280
Summary of Missed Doses of Paclitaxel, Arm A
All Treated Subjects
3.0290
Summary of Missed Doses of Carboplatin, Arm A
All Treated Subjects
3.0300
Summary of Missed Doses of Docetaxel, Arm B
All Treated Subjects
3.0310
Summary of Missed Doses of Pemetrexed, Arm C
All Treated Subjects
3.0320
Summary of Missed Doses of Cisplatin, Arm C
All Treated Subjects
3.0330
Summary of Dose Escalations of GSK3052230, Arm A
All Treated Subjects
3.0340
Summary of Dose Escalations of GSK3052230, Arm B
All Treated Subjects
3.0350
Summary of Dose Escalations of GSK3052230, Arm C
All Treated Subjects
3.0360
Summary of Dose Escalations of Paclitaxel, Arm A
All Treated Subjects
3.0370
Summary of Dose Escalations of Carboplatin, Arm A
All Treated Subjects
3.0380
Summary of Dose Escalations of Docetaxel, Arm B
All Treated Subjects
3.0390
Summary of Dose Escalations of Pemetrexed, Arm C
All Treated Subjects
3.0400
Summary of Dose Escalations of Cisplatin, Arm C
All Treated Subjects
3.1010
Adverse Event Overview, Arm A
All Treated Subjects
3.1020
Adverse Event Overview, Arm B
All Treated Subjects
3.1030
Adverse Event Overview, Arm C
All Treated Subjects
3.1040
Summary of All Adverse Events by System Organ Class, Arm A
All Treated Subjects
3.1050
Summary of All Adverse Events by System Organ Class, Arm B
All Treated Subjects
3.1060
Summary of All Adverse Events by System Organ Class, Arm C
All Treated Subjects
3.1070
Summary of All Adverse Events by Preferred Term, Arm A
All Treated Subjects


CONFIDENTIAL
FGF117360
65
No.
Title
Population 
3.1080
Summary of All Adverse Events by Preferred Term, Arm B
All Treated Subjects
3.1090
Summary of All Adverse Events by Preferred Term, Arm C
All Treated Subjects
3.1091
Summary of Adverse Events By Maximum Toxicity Grade, Arm A
All Treated Subjects
3.1092
Summary of Adverse Events By Maximum Toxicity Grade, Arm B
All Treated Subjects
3.1093
Summary of Adverse Events By Maximum Toxicity Grade, Arm C
All Treated Subjects
3.1094
Summary of Dose-Limiting Toxicities during the Determinative 
Period, Arm A
All Treated Subjects
3.1095
Summary of Dose-Limiting Toxicities during the Determinative 
Period, Arm B
All Treated Subjects
3.1096
Summary of Dose-Limiting Toxicities during the Determinative 
Period, Arm C
All Treated Subjects
3.1110
Summary of Adverse Events Related to Study Treatment by 
System Organ Class, Arm A
All Treated Subjects
3.1120
Summary of Adverse Events Related to Study Treatment by 
System Organ Class, Arm B
All Treated Subjects
3.1130
Summary of Adverse Events Related to Study Treatment by 
System Organ Class, Arm C
All Treated Subjects
3.1140
Summary of Adverse Events Related to Study Treatment by 
Preferred Term, Arm A
All Treated Subjects
3.1150
Summary of Adverse Events Related to Study Treatment by 
Preferred Term, Arm B
All Treated Subjects
3.1160
Summary of Adverse Events Related to Study Treatment by 
Preferred Term, Arm C
All Treated Subjects
3.1210
Summary of Serious Adverse Events, Arm A
All Treated Subjects
3.1220
Summary of Serious Adverse Events, Arm B
All Treated Subjects
3.1230
Summary of Serious Adverse Events, Arm C
All Treated Subjects
3.1310
Summary of Serious Adverse Events Related to Study Treatment, 
Arm A
All Treated Subjects
3.1320
Summary of Serious Adverse Events Related to Study Treatment, 
Arm B
All Treated Subjects
3.1330
Summary of Serious Adverse Events Related to Study Treatment, 
Arm C
All Treated Subjects
3.1410
Summary of Fatal Adverse Events, Arm A
All Treated Subjects
3.1420
Summary of Fatal Adverse Events, Arm B
All Treated Subjects
3.1430
Summary of Fatal Adverse Events, Arm C
All Treated Subjects
3.1440
Summary of Fatal Adverse Events Related to Study Treatment, 
Arm A
All Treated Subjects
3.1450
Summary of Fatal Adverse Events Related to Study Treatment, 
Arm B
All Treated Subjects
3.1460
Summary of Fatal Adverse Events Related to Study Treatment, 
Arm C
All Treated Subjects
3.1510
Summary of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment, Arm A
All Treated Subjects
3.1520
Summary of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment, Arm B
All Treated Subjects


CONFIDENTIAL
FGF117360
66
No.
Title
Population 
3.1530
Summary of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment, Arm C
All Treated Subjects
3.1540
Summary of Adverse Events Leading to Dose Reductions, Arm A
All Treated Subjects
3.1550
Summary of Adverse Events Leading to Dose Reductions, Arm B
All Treated Subjects
3.1560
Summary of Adverse Events Leading to Dose Reductions, Arm C
All Treated Subjects
3.1570
Summary of Adverse Events Leading to Dose Delays, Arm A
All Treated Subjects
3.1580
Summary of Adverse Events Leading to Dose Delays, Arm B
All Treated Subjects
3.1590
Summary of Adverse Events Leading to Dose Delays, Arm C
All Treated Subjects
3.2010
Summary of Deaths, Arm A
All Treated Subjects
3.2020
Summary of Deaths, Arm B
All Treated Subjects
3.2030
Summary of Deaths, Arm C
All Treated Subjects
3.3110
Summary of Chemistry Toxicities by Maximum Grade, Arm A
All Treated Subjects
3.3120
Summary of Chemistry Toxicities by Maximum Grade, Arm B
All Treated Subjects
3.3130
Summary of Chemistry Toxicities by Maximum Grade, Arm C
All Treated Subjects
3.3140
Summary of Clinical Chemistry Grade Changes from Baseline 
Grade, Arm A
All Treated Subjects
3.3150
Summary of Clinical Chemistry Grade Changes from Baseline 
Grade, Arm B
All Treated Subjects
3.3160
Summary of Clinical Chemistry Grade Changes from Baseline 
Grade, Arm C
All Treated Subjects
3.3170
Summary of Clinical Chemistry Changes from Baseline With 
Respect to the Normal Range, Arm A
All Treated Subjects
3.3180
Summary of Clinical Chemistry Changes from Baseline With 
Respect to the Normal Range, Arm B
All Treated Subjects
3.3190
Summary of Clinical Chemistry Changes from Baseline With 
Respect to the Normal Range, Arm C
All Treated Subjects
3.3210
Summary of Hematology Toxicities by Maximum Grade, Arm A
All Treated Subjects
3.3220
Summary of Hematology Toxicities by Maximum Grade, Arm B
All Treated Subjects
3.3230
Summary of Hematology Toxicities by Maximum Grade, Arm C
All Treated Subjects
3.3240
Summary of Hematology Grade Changes from Baseline Grade, 
Arm A
All Treated Subjects
3.3250
Summary of Hematology Grade Changes from Baseline Grade, 
Arm B
All Treated Subjects
3.3260
Summary of Hematology Grade Changes from Baseline Grade, 
Arm C
All Treated Subjects
3.3270
Summary of Hematology Changes from Baseline With Respect to 
the Normal Range, Arm A
All Treated Subjects
3.3280
Summary of Hematology Changes from Baseline With Respect to 
the Normal Range, Arm B
All Treated Subjects
3.3290
Summary of Hematology Changes from Baseline With Respect to 
the Normal Range, Arm C
All Treated Subjects
3.3310
Summary of Urinalysis Dipstick Results, Arm A
All Treated Subjects
3.3320
Summary of Urinalysis Dipstick Results, Arm B
All Treated Subjects
3.3330
Summary of Urinalysis Dipstick Results, Arm C
All Treated Subjects


CONFIDENTIAL
FGF117360
67
No.
Title
Population 
3.4010
Summary of Vital Signs, Arm A
All Treated Subjects
3.4015
Summary of Vital Signs, Arm B
All Treated Subjects
3.4020
Summary of Vital Signs, Arm C
All Treated Subjects
3.4025
Summary of Change from Baseline Vital Signs, Arm A
All Treated Subjects
3.4030
Summary of Change from Baseline Vital Signs, Arm B
All Treated Subjects
3.4035
Summary of Change from Baseline Vital Signs, Arm C
All Treated Subjects
3.4040
Summary of Changes in Heart Rate from Baseline, Arm A
All Treated Subjects
3.4045
Summary of Changes in Heart Rate from Baseline, Arm B
All Treated Subjects
3.4050
Summary of Changes in Heart Rate from Baseline, Arm C
All Treated Subjects
3.4055
Summary of Increases in Systolic Blood Pressure from Baseline, 
Arm A
All Treated Subjects
3.4060
Summary of Increases in Systolic Blood Pressure from Baseline, 
Arm B
All Treated Subjects
3.4065
Summary of Increases in Systolic Blood Pressure from Baseline, 
Arm C
All Treated Subjects
3.4070
Summary of increases in Diastolic Blood Pressure from Baseline, 
Arm A
All Treated Subjects
3.4075
Summary of increases in Diastolic Blood Pressure from Baseline, 
Arm B
All Treated Subjects
3.4080
Summary of increases in Diastolic Blood Pressure from Baseline, 
Arm C
All Treated Subjects
3.4085
Summary of Changes in Temperature from Baseline, Arm A
All Treated Subjects
3.4090
Summary of Changes in Temperature from Baseline, Arm B
All Treated Subjects
3.4095
Summary of Changes in Temperature from Baseline, Arm C
All Treated Subjects
3.4110
Summary of ECOG Performance Status, Arm A
All Treated Subjects
3.4120
Summary of ECOG Performance Status, Arm B
All Treated Subjects
3.4130
Summary of ECOG Performance Status, Arm C
All Treated Subjects
3.4140
Summary of Change in ECOG Performance Status from Baseline, 
Arm A
All Treated Subjects
3.4150
Summary of Change in ECOG Performance Status from Baseline, 
Arm B
All Treated Subjects
3.4160
Summary of Change in ECOG Performance Status from Baseline, 
Arm C
All Treated Subjects
3.4210
Summary of Left Ventricular Ejection Fraction Change from 
Baseline, Arm A
All Treated Subjects
3.6010
Summary of ECG findings, Arm A
All Treated Subjects
3.6020
Summary of ECG findings, Arm B
All Treated Subjects
3.6030
Summary of ECG findings, Arm C
All Treated Subjects
3.6040
Summary of ECG Values, Arm A
All Treated Subjects
3.6050
Summary of ECG Values, Arm B
All Treated Subjects
3.6060
Summary of ECG Values, Arm C
All Treated Subjects
3.6070
Summary of Increases in QTcF, Arm A
All Treated Subjects
3.6080
Summary of Increases in QTcF, Arm B
All Treated Subjects
3.6090
Summary of Increases in QTcF, Arm C
All Treated Subjects


CONFIDENTIAL
FGF117360
68
No.
Title
Population 
3.6100
Summary of Amount of Increase from Baseline Value in QTc, Arm 
A
All Treated Subjects
3.6110
Summary of Amount of Increase from Baseline Value in QTc, Arm 
B
All Treated Subjects
3.6120
Summary of Amount of Increase from Baseline Value in QTc, Arm 
C
All Treated Subjects
3.8010
Summary of Liver Chemistry Assessments for Subjects with Liver 
Signal/Event, Arm A
All Treated Subjects
3.8020
Summary of Liver Chemistry Assessments for Subjects with Liver 
Signal/Event, Arm B
All Treated Subjects
3.8030
Summary of Liver Chemistry Assessments for Subjects with Liver 
Signal/Event, Arm C
All Treated Subjects
3.8040
Summary of Hepatobiliary Laboratory Abnormalities, Arm A
All Treated Subjects
3.8050
Summary of Hepatobiliary Laboratory Abnormalities, Arm B
All Treated Subjects
3.8060
Summary of Hepatobiliary Laboratory Abnormalities, Arm C
All Treated Subjects
3.8070
Summary of Liver Event Information for RUCAM Score, Arm A
All Treated Subjects
3.8080
Summary of Liver Event Information for RUCAM Score, Arm B
All Treated Subjects
3.8090
Summary of Liver Event Information for RUCAM Score, Arm C
All Treated Subjects
3.8100
Summary of Immunogenicity Binding Assay Results, Arm A
All Treated Subjects
3.8110
Summary of Immunogenicity Binding Assay Results, Arm B
All Treated Subjects
3.8120
Summary of Immunogenicity Binding Assay Results, Arm C
All Treated Subjects
3.8130
Summary of Titration Assay Results, Arm A
All Treated Subjects
3.8140
Summary of Titration Assay Results, Arm B
All Treated Subjects
3.8150
Summary of Titration Assay Results, Arm C
All Treated Subjects
3.16100
Summary of Characteristics of Adverse Event of Special Interest 
Bowel Perforation, Arm A
All Treated Subjects
3.16101
Summary of Characteristics of Adverse Event of Special Interest 
Cardiac Valve Fibrosis, Arm A
All Treated Subjects
3.16102
Summary of Characteristics of Adverse Event of Special Interest 
Infusion Related Reactions, Arm A
All Treated Subjects
3.16103
Summary of Characteristics of Adverse Event of Special Interest 
Hematologic Toxicities, Arm A
All Treated Subjects
3.16104
Summary of Characteristics of Adverse Event of Special Interest 
Nephrotoxicity, Arm A
All Treated Subjects
3.16105
Summary of Characteristics of Adverse Event of Special Interest 
Healing Abnormalities, Arm A
All Treated Subjects
3.16106
Summary of Characteristics of Adverse Event of Special Interest 
Hearing and Vestibular Disorders, Arm A
All Treated Subjects
3.16107
Summary of Characteristics of Adverse Event of Special Interest 
Hypothyroidism, Arm A
All Treated Subjects
3.16108
Summary of Characteristics of Adverse Event of Special Interest 
Ototoxicty, Arm A
All Treated Subjects
3.16109
Summary of Characteristics of Adverse Event of Special Interest 
Peripheral Neuropathy, Arm A
All Treated Subjects
3.16110
Summary of Characteristics of Adverse Event of Special Interest 
Bowel Perforation, Arm B
All Treated Subjects


CONFIDENTIAL
FGF117360
69
No.
Title
Population 
3.16111
Summary of Characteristics of Adverse Event of Special Interest 
Cardiac Valve Fibrosis, Arm B
All Treated Subjects
3.16112
Summary of Characteristics of Adverse Event of Special Interest 
Infusion Related Reactions, Arm B
All Treated Subjects
3.16113
Summary of Characteristics of Adverse Event of Special Interest 
Hematologic Toxicities, Arm B
All Treated Subjects
3.16114
Summary of Characteristics of Adverse Event of Special Interest 
Nephrotoxicity, Arm B
All Treated Subjects
3.16115
Summary of Characteristics of Adverse Event of Special Interest 
Healing Abnormalities, Arm B
All Treated Subjects
3.16116
Summary of Characteristics of Adverse Event of Special Interest 
Hearing and Vestibular Disorders, Arm B
All Treated Subjects
3.16117
Summary of Characteristics of Adverse Event of Special Interest 
Hypothyroidism, Arm B
All Treated Subjects
3.16118
Summary of Characteristics of Adverse Event of Special Interest 
Ototoxicty, Arm B
All Treated Subjects
3.16119
Summary of Characteristics of Adverse Event of Special Interest 
Peripheral Neuropathy, Arm B
All Treated Subjects
3.16120
Summary of Characteristics of Adverse Event of Special Interest 
Bowel Perforation, Arm C
All Treated Subjects
3.16121
Summary of Characteristics of Adverse Event of Special Interest 
Cardiac Valve Fibrosis, Arm C
All Treated Subjects
3.16122
Summary of Characteristics of Adverse Event of Special Interest 
Infusion Related Reactions, Arm C
All Treated Subjects
3.16123
Summary of Characteristics of Adverse Event of Special Interest 
Hematologic Toxicities, Arm C
All Treated Subjects
3.16124
Summary of Characteristics of Adverse Event of Special Interest 
Nephrotoxicity, Arm C
All Treated Subjects
3.16125
Summary of Characteristics of Adverse Event of Special Interest 
Healing Abnormalities, Arm C
All Treated Subjects
3.16126
Summary of Characteristics of Adverse Event of Special Interest 
Hearing and Vestibular Disorders, Arm C
All Treated Subjects
3.16127
Summary of Characteristics of Adverse Event of Special Interest 
Hypothyroidism, Arm C
All Treated Subjects
3.16128
Summary of Characteristics of Adverse Event of Special Interest 
Ototoxicty, Arm C
All Treated Subjects
3.16129
Summary of Characteristics of Adverse Event of Special Interest 
Peripheral Neuropathy, Arm C
All Treated Subjects
3.16200
Summary of Onset and Duration of the First Occurrence of 
Adverse Event of Special Interest Bowel Perforation, Arm A
All Treated Subjects
3.16201
Summary of Onset and Duration of the First Occurrence of 
Adverse Event of Special Interest Cardiac Valve Fibrosis, Arm A
All Treated Subjects
3.16202
Summary of Onset and Duration of the First Occurrence of 
Adverse Event of Special Interest Infusion Related Reactions, 
Arm A
All Treated Subjects
3.16203
Summary of Onset and Duration of the First Occurrence of 
Adverse Event of Special Interest Hematologic Toxicities, Arm A
All Treated Subjects


CONFIDENTIAL
FGF117360
70
No.
Title
Population 
3.16204
Summary of Onset and Duration of the First Occurrence of 
Adverse Event of Special Interest Nephrotoxicity, Arm A
All Treated Subjects
3.16205
Summary of Onset and Duration of the First Occurrence of 
Adverse Event of Special Interest Healing Abnormalities, Arm A
All Treated Subjects
3.16206
Summary of Onset and Duration of the First Occurrence of 
Adverse Event of Special Interest Hearing and Vestibular 
Disorders, Arm A
All Treated Subjects
3.16207
Summary of Onset and Duration of the First Occurrence of 
Adverse Event of Special Interest Hypothyroidism, Arm A
All Treated Subjects
3.16208
Summary of Onset and Duration of the First Occurrence of 
Adverse Event of Special Interest Ototoxicty, Arm A
All Treated Subjects
3.16209
Summary of Onset and Duration of the First Occurrence of 
Adverse Event of Special Interest Peripheral Neuropathy, Arm A
All Treated Subjects
3.16210
Summary of Onset and Duration of the First Occurrence of 
Adverse Event of Special Interest Bowel Perforation, Arm B
All Treated Subjects
3.16211
Summary of Onset and Duration of the First Occurrence of 
Adverse Event of Special Interest Cardiac Valve Fibrosis, Arm B
All Treated Subjects
3.16212
Summary of Onset and Duration of the First Occurrence of 
Adverse Event of Special Interest Infusion Related Reactions, 
Arm B
All Treated Subjects
3.16213
Summary of Onset and Duration of the First Occurrence of 
Adverse Event of Special Interest Hematologic Toxicities, Arm B
All Treated Subjects
3.16214
Summary of Onset and Duration of the First Occurrence of 
Adverse Event of Special Interest Nephrotoxicity, Arm B
All Treated Subjects
3.16215
Summary of Onset and Duration of the First Occurrence of 
Adverse Event of Special Interest Healing Abnormalities, Arm B
All Treated Subjects
3.16216
Summary of Onset and Duration of the First Occurrence of 
Adverse Event of Special Interest Hearing and Vestibular 
Disorders, Arm B
All Treated Subjects
3.16217
Summary of Onset and Duration of the First Occurrence of 
Adverse Event of Special Interest Hypothyroidism, Arm B
All Treated Subjects
3.16218
Summary of Onset and Duration of the First Occurrence of 
Adverse Event of Special Interest Ototoxicty, Arm B
All Treated Subjects
3.16219
Summary of Onset and Duration of the First Occurrence of 
Adverse Event of Special Interest Peripheral Neuropathy, Arm B
All Treated Subjects
3.16220
Summary of Onset and Duration of the First Occurrence of 
Adverse Event of Special Interest Bowel Perforation, Arm C
All Treated Subjects
3.16221
Summary of Onset and Duration of the First Occurrence of 
Adverse Event of Special Interest Cardiac Valve Fibrosis, Arm C
All Treated Subjects
3.16222
Summary of Onset and Duration of the First Occurrence of 
Adverse Event of Special Interest Infusion Related Reactions, 
Arm C
All Treated Subjects
3.16223
Summary of Onset and Duration of the First Occurrence of 
Adverse Event of Special Interest Hematologic Toxicities, Arm C
All Treated Subjects
3.16224
Summary of Onset and Duration of the First Occurrence of 
Adverse Event of Special Interest Nephrotoxicity, Arm C
All Treated Subjects
3.16225
Summary of Onset and Duration of the First Occurrence of 
Adverse Event of Special Interest Healing Abnormalities, Arm C
All Treated Subjects


CONFIDENTIAL
FGF117360
71
No.
Title
Population 
3.16226
Summary of Onset and Duration of the First Occurrence of 
Adverse Event of Special Interest Hearing and Vestibular 
Disorders, Arm C
All Treated Subjects
3.16227
Summary of Onset and Duration of the First Occurrence of 
Adverse Event of Special Interest Hypothyroidism, Arm C
All Treated Subjects
3.16228
Summary of Onset and Duration of the First Occurrence of 
Adverse Event of Special Interest Ototoxicty, Arm C
All Treated Subjects
3.16229
Summary of Onset and Duration of the First Occurrence of 
Adverse Event of Special Interest Peripheral Neuropathy, Arm C
All Treated Subjects
20.1.5.
Safety Figures
No.
Title
Population 
13.0010
Plot of Duration of Study Treatment, Arm A
All Treated Subjects
13.0020
Plot of Duration of Study Treatment, Arm B
All Treated Subjects
13.0030
Plot of Duration of Study Treatment, Arm C
All Treated Subjects
13.0040
QTcF Shifts from Baseline to Worst-case Post Baseline, Arm A
All Treated Subjects
13.0050
QTcF Shifts from Baseline to Worst-case Post Baseline, Arm B
All Treated Subjects
13.0060
QTcF Shifts from Baseline to Worst-case Post Baseline, Arm C
All Treated Subjects
13.0070
Figure of LFT Patient Profiles for Possible Hy’s Law Subjects, 
Arm A
All Treated Subjects
13.0080
Figure of LFT Patient Profiles for Possible Hy’s Law Subjects, 
Arm B
All Treated Subjects
13.0090
Figure of LFT Patient Profiles for Possible Hy’s Law Subjects, 
Arm C
All Treated Subjects
13.0100
Figure of Maximum Total Bilirubin vs Maximum ALT – eDISH Plot, 
Arm A
All Treated Subjects
13.0110
Figure of Maximum Total Bilirubin vs Maximum ALT – eDISH Plot, 
Arm B
All Treated Subjects
13.0120
Figure of Maximum Total Bilirubin vs Maximum ALT – eDISH Plot, 
Arm C
All Treated Subjects
13.0130
Trellis Display of Maximum versus Baseline LFT, Arm A
All Treated Subjects
13.0140
Trellis Display of Maximum versus Baseline LFT, Arm B
All Treated Subjects
13.0150
Trellis Display of Maximum versus Baseline LFT, Arm C
All Treated Subjects
13.0160
Matrix Display of Comparative LFT Scatter Plots, Arm A
All Treated Subjects
13.0170
Matrix Display of Comparative LFT Scatter Plots, Arm B
All Treated Subjects
13.0180
Matrix Display of Comparative LFT Scatter Plots, Arm C
All Treated Subjects
13.01900
Cumulative Incidence Plot of Bowel Perforation from Baseline
All Treated Subjects
13.01901
Cumulative Incidence Plot of Cardiac Valve Fibrosis from 
Baseline
All Treated Subjects
13.01902
Cumulative Incidence Plot of Infusiin Related Reactions from 
Baseline
All Treated Subjects
13.01903
Cumulative Incidence Plot of Nephrotoxicity from Baseline
All Treated Subjects
13.01904
Cumulative Incidence Plot of Hematologic Toxicities from 
Baseline
All Treated Subjects
13.01905
Cumulative Incidence Plot of Healing Abnormalities from Baseline
All Treated Subjects


CONFIDENTIAL
FGF117360
72
No.
Title
Population 
13.01906
Cumulative Incidence Plot of Hearing and Vestibular Disorders 
from Baseline
All Treated Subjects
13.01907
Cumulative Incidence Plot of Hypothyroidism from Baseline
All Treated Subjects
13.01908
Cumulative Incidence Plot of Ototoxicity from Baseline
All Treated Subjects
13.01909
Cumulative Incidence Plot of Peripheral Neuropathy from 
Baseline
All Treated Subjects
20.1.6.
Pharmacokinetics Tables
No.
Title
Population 
5.0010
Summary of GSK3052230 Plasma Pharmacokinetic 
Concentration-Time Data [ng/mL], Arm A
PK
5.0020
Summary of GSK3052230 Plasma Pharmacokinetic 
Concentration-Time Data [ng/mL], Arm B
PK
5.0030
Summary of GSK3052230 Plasma Pharmacokinetic 
Concentration-Time Data [ng/mL], Arm C
PK
5.0040
Summary of Paclitaxel Plasma Pharmacokinetic Concentration-
Time Data [ng/mL], Arm A
PK
5.0050
Summary of Docetaxel Plasma Pharmacokinetic Concentration-
Time Data [ng/mL], Arm B
PK
5.0060
Summary of Pemetrexed Plasma Pharmacokinetic Concentration-
Time Data [ng/mL], Arm C
PK
5.1010
Summary of Derived GSK3052230 Plasma Pharmacokinetic 
Parameters (non-transformed and log-transformed), Subjects with 
Extensive PK Sampling, Arm A
PK
5.1020
Summary of Derived GSK3052230 Plasma Pharmacokinetic 
Parameters (non-transformed and log-transformed), Subjects with 
Extensive PK Sampling, Arm B
PK
5.1030
Summary of Derived GSK3052230 Plasma Pharmacokinetic 
Parameters (non-transformed and log-transformed), Subjects with 
Extensive PK Sampling, Arm C
PK
20.1.7.
Pharmacokinetics Figures
Table No.
Title
Population 
15.0010
Mean GSK3052230 Plasma Concentration-Time Plots (Linear 
and Semi-log) for C1D1 through C2D1, Subjects with Extensive 
PK Sampling, Arm A
PK
15.0020
Mean GSK3052230 Plasma Concentration-Time Plots (Linear 
and Semi-log) for C1D1 through C2D1, Subjects with Extensive 
PK Sampling, Arm B
PK
15.0030
Mean GSK3052230 Plasma Concentration-Time Plots (Linear 
and Semi-log) for C1D1 through C2D1, Subjects with Extensive 
PK Sampling, Arm C
PK


CONFIDENTIAL
FGF117360
73
Table No.
Title
Population 
15.0040
Mean GSK3052230 Plasma Concentration-Time Plots (Linear 
and Semi-log) for C1D1, Subjects with Extensive PK Sampling, 
Arm A
PK
15.0050
Mean GSK3052230 Plasma Concentration-Time Plots (Linear 
and Semi-log) for C1D1, Subjects with Extensive PK Sampling, 
Arm B
PK
15.0060
Mean GSK3052230 Plasma Concentration-Time Plots (Linear 
and Semi-log) for C1D1, Subjects with Extensive PK Sampling, 
Arm C
PK
15.0040
Median GSK3052230 Plasma Concentration-Time Plots (Linear 
and Semi-log) for C1D1 through C2D1, Subjects with Extensive 
PK Sampling, Arm A
PK
15.0050
Median GSK3052230 Plasma Concentration-Time Plots (Linear 
and Semi-log) for C1D1 through C2D1, Subjects with Extensive 
PK Sampling, Arm B
PK
15.0060
Median GSK3052230 Plasma Concentration-Time Plots (Linear 
and Semi-log) for C1D1 through C2D1, Subjects with Extensive 
PK Sampling, Arm C
PK
15.0070
Median GSK3052230 Plasma Concentration-Time Plots (Linear 
and Semi-log) for C1D1, Subjects with Extensive PK Sampling, 
Arm A
PK
15.0080
Median GSK3052230 Plasma Concentration-Time Plots (Linear 
and Semi-log) for C1D1, Subjects with Extensive PK Sampling, 
Arm B
PK
15.0090
Median GSK3052230 Plasma Concentration-Time Plots (Linear 
and Semi-log) for C1D1, Subjects with Extensive PK Sampling, 
Arm C
PK
15.1010
Box and Whisker Plot of Cycle 1 Day 8 GSK3052230 Pre-Infusion 
Plasma Concentration at the Recommended Phase 2 Dose By 
Study Arm, Arms A, B, and C
PK
15.1020
Box and Whisker Plot of Cycle 2 Day 1 GSK3052230 Pre-Infusion 
Plasma Concentration at the Recommended Phase 2 Dose By 
Study Arm, Arms A, B, and C
PK
15.1030
Box and Whisker Plot of Cycle 4 Day1 GSK3052230 Pre-Infusion 
Plasma Concentration at the Recommended Phase 2 Dose By 
Study Arm, Arms A, B, and C
PK
15.1040
Box and Whisker Plot of Cycle 6 Day 1 GSK3052230 Pre-Infusion 
Plasma Concentration at the Recommended Phase 2 Dose By 
Study Arm, Arms A, B, and C
PK
15.1050
Box and Whisker Plot of Cycle 12 Day 1 GSK3052230 Pre-
Infusion Plasma Concentration at the Recommended Phase 2 
Dose By Study Arm, Arms A, B, and C
PK
15.1060
Box and Whisker Plot of Cycle 1 Day 8 End of GSK3052230 
Infusion Plasma Concentration at the Recommended Phase 2 
Dose By Study Arm, Arms A, B, and C
PK
15.1070
Box and Whisker Plot of Cycle 2 Day 1  End of GSK3052230 
Infusion  Plasma Concentration at the Recommended Phase 2 
Dose By Study Arm, Arms A, B, and C
PK


CONFIDENTIAL
FGF117360
74
Table No.
Title
Population 
15.1080
Box and Whisker Plot of Cycle 4 Day1  End of GSK3052230 
Infusion  Plasma Concentration at the Recommended Phase 2 
Dose By Study Arm, Arms A, B, and C
PK
15.1090
Box and Whisker Plot of Cycle 6 Day 1  End of GSK3052230 
Infusion  Plasma Concentration at the Recommended Phase 2 
Dose By Study Arm, Arms A, B, and C
PK
15.1091
Box and Whisker Plot of Cycle 12 Day 1  End of GSK3052230 
Infusion  Plasma Concentration at the Recommended Phase 2 
Dose By Study Arm, Arms A, B, and C
PK
15.2010
Individual GSK3052230 Plasma Concentration-Time Plots (Linear 
and Semi-log) for C1D1 through C2D1, Subjects with Extensive 
PK Sampling, Arm A
PK
15.2020
Individual GSK3052230 Plasma Concentration-Time Plots (Linear 
and Semi-log) for C1D1 through C2D1, Subjects with Extensive 
PK Sampling, Arm B
PK
15.2030
Individual GSK3052230 Plasma Concentration-Time Plots (Linear 
and Semi-log) for C1D1 through C2D1, Subjects with Extensive 
PK Sampling, Arm C
PK
15.2010
Individual GSK3052230 Plasma Concentration-Time Plots (Linear 
and Semi-log) for C1D1, Subjects with Extensive PK Sampling, 
Arm A
PK
15.2020
Individual GSK3052230 Plasma Concentration-Time Plots (Linear 
and Semi-log) for C1D1, Subjects with Extensive PK Sampling, 
Arm B
PK
15.2030
Individual GSK3052230 Plasma Concentration-Time Plots (Linear 
and Semi-log) for C1D1, Subjects with Extensive PK Sampling, 
Arm C
PK
20.1.8.
Pharmacodynamic Tables
No.
Title
Population 
6.0010
Summary of FGFR1 Quantitative Measurements, Arm A
PD
6.0020
Summary of FGFR1 Quantitative Measurements, Arm B
PD
6.0030
Summary of FGFR1 Quantitative Measurements, Arm A&B
PD
6.0040
Summary of FGFR1 Amplification Rates, Arm A&B
PD
20.1.9.
Pharmacodynamic Figures
Table No.
Title
Population 
16.0010
Plot of FGFR1/CEP Ratio vs. Average FGFR1 Signial/Cell, Arm 
A&B
PD
16.0020
Plot of FGFR1/CEP Ratio vs. %Cells >/=5 FGFR1 Sig/Nucle, Arm 
A&B
PD
16.0030
Plot of Average FGFR1 Signals/Cell vs. %Cells >/=5 FGFR1 
Sig/Nuclei, Arm A&B
PD
16.0040
Plot of Best Response by Average FGFR1 Signals, Arm A
PD


CONFIDENTIAL
FGF117360
75
Table No.
Title
Population 
16.0050
Plot of Best Response by Average FGFR1 Signals, Arm B
PD
16.0060
Plot of Best Response by FGFR1/CEP Ratio, Arm A
PD
16.0070
Plot of Best Response by FGFR1/CEP Ratio, Arm B
PD
16.0080
Plot of Best Response by Percentage of Cells >/=5 FGFR1 
Sig/Nuclei, Arm A
PD
16.0090
Plot of Best Response by Percentage of Cells >/=5 FGFR1 
Sig/Nuclei, Arm B
PD
16.0100
Plot of Duration of Treatment vs. Average FGFR1 Signals, Arm A
PD
16.0110
Plot of Duration of Treatment vs. Average FGFR1 Signals, Arm B
PD
16.0120
Plot of Duration of Treatment vs. FGFR1/CEP Ratio, Arm A
PD
16.0130
Plot of Duration of Treatment vs. FGFR1/CEP Ratio, Arm B
PD
16.0140
Plot of Duration of Treatment vs. Percentage of Cells >/=5 FGFR1 
Sig/Nuclei, Arm A
PD
16.0150
Plot of Duration of Treatment vs. Percentage of Cells >/=5 FGFR1 
Sig/Nuclei, Arm B
PD
16.0160
Plot of Progression Free Survival vs. Average FGFR1 Signals, 
Arm A
PD
16.0170
Plot of Progression Free Survival vs. Average FGFR1 Signals, 
Arm B
PD
16.0180
Plot of Progression Free Survival vs. FGFR1/CEP Ratio, Arm A
PD
16.0190
Plot of Progression Free Survival vs. FGFR1/CEP Ratio, Arm B
PD
16.0200
Plot of Progression Free Survival vs. Percentage of Cells >/=5 
FGFR1 Sig/Nuclei, Arm A
PD
16.0210
Plot of Progression Free Survival vs. Percentage of Cells >/=5 
FGFR1 Sig/Nuclei, Arm B
PD
16.0220
Plot of H-score by Best Response, Arm C
PD
16.0230
Plot of Duration of Treatment vs. H-score, Arm C
PD
16.0240
Plot of Progression Free Survival vs. H-score, Arm C
PD
20.1.10.
ICH Listings
Section
Listing No.
Title
Population
Study Pop
21.0010
Listing of Planned and Actual Treatment, Arm A
All Treated Subjects
Study Pop
21.0020
Listing of Planned and Actual Treatment, Arm B
All Treated Subjects
Study Pop
21.0030
Listing of Planned and Actual Treatment, Arm C
All Treated Subjects
Study Pop
21.0040
Listing of Subjects Excluded from Analysis Populations, 
Arm A
All Screened 
Subjects
Study Pop
21.0050
Listing of Subjects Excluded from Analysis Populations, 
Arm B
All Screened 
Subjects
Study Pop
21.0060
Listing of Subjects Excluded from Analysis Populations, 
Arm C
All Screened 
Subjects
Study Pop
21.0070
Listing of Reasons for Study Withdrawal, Arm A
All Treated Subjects
Study Pop
21.0080
Listing of Reasons for Study Withdrawal, Arm B
All Treated Subjects
Study Pop
21.0090
Listing of Reasons for Study Withdrawal, Arm C
All Treated Subjects


CONFIDENTIAL
FGF117360
76
Section
Listing No.
Title
Population
Study Pop
21.0100
Listing of Study Treatment Discontinuation Record, Arm A
All Treated Subjects
Study Pop
21.0110
Listing of Study Treatment Discontinuation Record, Arm B
All Treated Subjects
Study Pop
21.0120
Listing of Study Treatment Discontinuation Record, Arm C
All Treated Subjects
Study Pop
21.0130
Listing of Subjects with Inclusion/Exclusion Criteria 
Deviations, Arm A
All Treated Subjects
Study Pop
21.0140
Listing of Subjects with Inclusion/Exclusion Criteria 
Deviations, Arm B
All Treated Subjects
Study Pop
21.0150
Listing of Subjects with Inclusion/Exclusion Criteria 
Deviations, Arm C
All Treated Subjects
Study Pop
21.0160
Listing of Protocol Deviations, Arm A
All Treated Subjects
Study Pop
21.0170
Listing of Protocol Deviations, Arm B
All Treated Subjects
Study Pop
21.0180
Listing of Protocol Deviations, Arm C
All Treated Subjects
Study Pop
21.0190
Listing of Demographic Characteristics, Arm A
All Treated Subjects
Study Pop
21.0200
Listing of Demographic Characteristics, Arm B
All Treated Subjects
Study Pop
21.0210
Listing of Demographic Characteristics, Arm C
All Treated Subjects
Study Pop
21.0220
Listing of Race, Arm A
All Treated Subjects
Study Pop
21.0230
Listing of Race, Arm B
All Treated Subjects
Study Pop
21.0240
Listing of Race, Arm C
All Treated Subjects
Efficacy
22.0010
Listing of Investigator-Assessed Target Lesion 
Assessments (RECIST 1.1 Criteria), Arm A
All Treated Subjects
Efficacy
22.0020
Listing of Investigator-Assessed Target Lesion 
Assessments (RECIST 1.1 Criteria), Arm B
All Treated Subjects
Efficacy
22.0030
Listing of Investigator-Assessed Target Lesion 
Assessments (RECIST 1.1 Criteria), Arm C
All Treated Subjects
Efficacy
22.0040
Listing of Investigator-Assessed Target Lesion 
Assessments (Modified RECIST Criteria), Arm C
All Treated Subjects
Efficacy
22.0050
Listing of Investigator-Assessed Non Target Lesion 
Assessments (RECIST 1.1 Criteria), Arm A
All Treated Subjects
Efficacy
22.0060
Listing of Investigator-Assessed Non Target Lesion 
Assessments (RECIST 1.1 Criteria), Arm B
All Treated Subjects
Efficacy
22.0070
Listing of Investigator-Assessed Non Target Lesion 
Assessments (RECIST 1.1 Criteria), Arm C
All Treated Subjects
Efficacy
22.0080
Listing of Investigator-Assessed Non Target Lesion 
Assessments (Modified RECIST Criteria), Arm C
All Treated Subjects
Efficacy
22.0090
Listing of Investigator-Assessed New Lesions (RECIST 1.1 
Criteria), Arm A
All Treated Subjects
Efficacy
22.0100
Listing of Investigator-Assessed New Lesions (RECIST 1.1 
Criteria), Arm B
All Treated Subjects
Efficacy
22.0110
Listing of Investigator-Assessed New Lesions (RECIST 1.1 
Criteria), Arm C
All Treated Subjects
Efficacy
22.0120
Listing of Investigator-Assessed New Lesions (Modified 
RECIST Criteria), Arm C
All Treated Subjects
Efficacy
22.0130
Listing of Investigator-Assessed Tumor Responses with 
confirmation (RECIST1.1 Criteria), Arm A
All Treated Subjects
Efficacy
22.0140
Listing of Investigator-Assessed Tumor Responses with 
confirmation (RECIST1.1 Criteria), Arm B
All Treated Subjects


CONFIDENTIAL
FGF117360
77
Section
Listing No.
Title
Population
Efficacy
22.0150
Listing of Investigator-Assessed Tumor Responses with 
confirmation (RECIST1.1 Criteria), Arm C
All Treated Subjects
Efficacy
22.0160
Listing of Investigator-Assessed Tumor Responses with 
confirmation (Modified RECIST Criteria), Arm C
All Treated Subjects
Efficacy
22.0170
Listing of Progression-Free Survival, Arm A
All Treated Subjects
Efficacy
22.0180
Listing of Progression-Free Survival, Arm B
All Treated Subjects
Efficacy
22.0190
Listing of Progression-Free Survival, Arm C
All Treated Subjects
Safety
23.0010
Listing of Exposure to GSK3052230, Arm A
All Treated Subjects
Safety
23.0020
Listing of Exposure to GSK3052230, Arm B
All Treated Subjects
Safety
23.0030
Listing of Exposure to GSK3052230, Arm C
All Treated Subjects
Safety
23.0040
Listing of Exposure to Paclitaxel, Arm A
All Treated Subjects
Safety
23.0050
Listing of Exposure to Carboplatin, Arm A
All Treated Subjects
Safety
23.0060
Listing of Exposure to Docetaxel, Arm B
All Treated Subjects
Safety
23.0070
Listing of Exposure to Pemetrexed, Arm C
All Treated Subjects
Safety
23.0080
Listing of Exposure to Cisplatin, Arm C
All Treated Subjects
Safety
23.0090
Listing of Dose Reductions, Arm A
All Treated Subjects
Safety
23.0100
Listing of Dose Reductions, Arm B
All Treated Subjects
Safety
23.0110
Listing of Dose Reductions, Arm C
All Treated Subjects
Safety
23.0120
Listing of Dose Delays, Arm A
All Treated Subjects
Safety
23.0130
Listing of Dose Delays, Arm B
All Treated Subjects
Safety
23.0140
Listing of Dose Delays, Arm C
All Treated Subjects
Safety
23.0150
Listing of Missed Doses, Arm A
All Treated Subjects
Safety
23.0160
Listing of Missed Doses, Arm B
All Treated Subjects
Safety
23.0170
Listing of Missed Doses, Arm C
All Treated Subjects
Safety
23.0180
Listing of Incomplete Infusions, Arm A
All Treated Subjects
Safety
23.0190
Listing of Incomplete Infusions, Arm B
All Treated Subjects
Safety
23.0200
Listing of Incomplete Infusions, Arm C
All Treated Subjects
Safety
23.0210
Listing of Infusion Interruptions, Arm A
All Treated Subjects
Safety
23.0220
Listing of Infusion Interruptions, Arm B
All Treated Subjects
Safety
23.0230
Listing of Infusion Interruptions, Arm C
All Treated Subjects
Safety
23.0240
Listing of Dose Escalations, Arm A
All Treated Subjects
Safety
23.0250
Listing of Dose Escalations, Arm B
All Treated Subjects
Safety
23.0260
Listing of Dose Escalations, Arm C
All Treated Subjects
Safety
23.0270
Listing of the Relationship Between System Organ Class, 
Preferred Term, and Verbatim Text, Arm A
All Treated Subjects
Safety
23.0280
Listing of the Relationship Between System Organ Class, 
Preferred Term, and Verbatim Text, Arm B
All Treated Subjects
Safety
23.0290
Listing of the Relationship Between System Organ Class, 
Preferred Term, and Verbatim Text, Arm C
All Treated Subjects
Safety
23.0300
Listing of Subject Numbers for Individual Adverse Events, 
Arm A
All Treated Subjects
Safety
23.0310
Listing of Subject Numbers for Individual Adverse Events, 
Arm B
All Treated Subjects
Safety
23.0320
Listing of Subject Numbers for Individual Adverse Events, 
All Treated Subjects


CONFIDENTIAL
FGF117360
78
Section
Listing No.
Title
Population
Arm C
Safety
23.0330
Listing of All Adverse Events with Grade Change Details, 
Arm A
All Treated Subjects
Safety
23.0340
Listing of All Adverse Events with Grade Change Details, 
Arm B
All Treated Subjects
Safety
23.0350
Listing of All Adverse Events with Grade Change Details, 
Arm C
All Treated Subjects
Safety
23.0360
Listing of Fatal Serious Adverse Events, Arm A
All Treated Subjects
Safety
23.0370
Listing of Fatal Serious Adverse Events, Arm B
All Treated Subjects
Safety
23.0380
Listing of Fatal Serious Adverse Events, Arm C
All Treated Subjects
Safety
23.0390
Listing of Non-Fatal Serious Adverse Events, Arm A
All Treated Subjects
Safety
23.0400
Listing of Non-Fatal Serious Adverse Events, Arm B
All Treated Subjects
Safety
23.0410
Listing of Non-Fatal Serious Adverse Events, Arm C
All Treated Subjects
Safety
23.0420
Listing of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment, Arm A
All Treated Subjects
Safety
23.0430
Listing of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment, Arm B
All Treated Subjects
Safety
23.0440
Listing of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment, Arm C
All Treated Subjects
Safety
23.0450
Listing of Adverse Events Leading to Dose Delays, Arm A
All Treated Subjects
Safety
23.0460
Listing of Adverse Events Leading to Dose Delays, Arm B
All Treated Subjects
Safety
23.0470
Listing of Adverse Events Leading to Dose Delays, Arm C
All Treated Subjects
Safety
23.0480
Listing of Adverse Events Leading to Dose Reductions, 
Arm A
All Treated Subjects
Safety
23.0490
Listing of Adverse Events Leading to Dose Reductions, 
Arm B
All Treated Subjects
Safety
23.0500
Listing of Adverse Events Leading to Dose Reductions, 
Arm C
All Treated Subjects
Safety
23.0510
Listing of Dose-Limiting Adverse Events (DLTs), Arm A
All Treated Subjects
Safety
23.0520
Listing of Dose-Limiting Adverse Events (DLTs), Arm B
All Treated Subjects
Safety
23.0530
Listing of Dose-Limiting Adverse Events (DLTs), Arm C
All Treated Subjects
Safety
23.0540
Listing of Dose-Limiting Toxicities during the Determinative 
Period, Arm A
All Treated Subjects
Safety
23.0550
Listing of Dose-Limiting Toxicities during the Determinative 
Period, Arm B
All Treated Subjects
Safety
23.0560
Listing of Dose-Limiting Toxicities during the Determinative 
Period, Arm C
All Treated Subjects
Safety
23.05700
Listing of Adverse Event or Condition of Bowel Perforation, 
Arm A
All Treated Subjects
Safety
23.05701
Listing of Adverse Event or Condition of Cardiac Valve 
Fibrosis, Arm A
All Treated Subjects
Safety
23.05702
Listing of Adverse Event or Condition of Infusion Related 
Reactions, Arm A
All Treated Subjects
Safety
23.05703
Listing of Adverse Event or Condition of Hematologic 
Toxicities, Arm A
All Treated Subjects
Safety
23.05704
Listing of Adverse Event or Condition of Nephrotoxicity, 
Arm A
All Treated Subjects
Safety
23.05705
Listing of Adverse Event or Condition of Healing 
Abnormalities, Arm A
All Treated Subjects


CONFIDENTIAL
FGF117360
79
Section
Listing No.
Title
Population
Safety
23.05706
Listing of Adverse Event or Condition of Hearing and 
Vestibular Disorders, Arm A
All Treated Subjects
Safety
23.05707
Listing of Adverse Event or Condition of Hypothyroidism, 
Arm A
All Treated Subjects
Safety
23.05708
Listing of Adverse Event or Condition of Ototoxicty, Arm A
All Treated Subjects
Safety
23.05709
Listing of Adverse Event or Condition of Peripheral 
Neuropathy, Arm A
All Treated Subjects
Safety
23.05710
Listing of Adverse Event or Condition of Bowel Perforation, 
Arm B
All Treated Subjects
Safety
23.05711
Listing of Adverse Event or Condition of Cardiac Valve 
Fibrosis, Arm B
All Treated Subjects
Safety
23.05712
Listing of Adverse Event or Condition of Infusion Related 
Reactions, Arm B
All Treated Subjects
Safety
23.05713
Listing of Adverse Event or Condition of Hematologic 
Toxicities, Arm B
All Treated Subjects
Safety
23.05714
Listing of Adverse Event or Condition of Nephrotoxicity, 
Arm B
All Treated Subjects
Safety
23.05715
Listing of Adverse Event or Condition of Healing 
Abnormalities, Arm B
All Treated Subjects
Safety
23.05716
Listing of Adverse Event or Condition of Hearing and 
Vestibular Disorders, Arm B
All Treated Subjects
Safety
23.05717
Listing of Adverse Event or Condition of Hypothyroidism, 
Arm B
All Treated Subjects
Safety
23.05718
Listing of Adverse Event or Condition of Ototoxicty, Arm B
All Treated Subjects
Safety
23.05719
Listing of Adverse Event or Condition of Peripheral 
Neuropathy, Arm B
All Treated Subjects
Safety
23.05720
Listing of Adverse Event or Condition of Bowel Perforation, 
Arm C
All Treated Subjects
Safety
23.05721
Listing of Adverse Event or Condition of Cardiac Valve 
Fibrosis, Arm C
All Treated Subjects
Safety
23.05722
Listing of Adverse Event or Condition of Infusion Related 
Reactions, Arm C
All Treated Subjects
Safety
23.05723
Listing of Adverse Event or Condition of Hematologic 
Toxicities, Arm C
All Treated Subjects
Safety
23.05724
Listing of Adverse Event or Condition of Nephrotoxicity, 
Arm C
All Treated Subjects
Safety
23.05725
Listing of Adverse Event or Condition of Healing 
Abnormalities, Arm C
All Treated Subjects
Safety
23.05726
Listing of Adverse Event or Condition of Hearing and 
Vestibular Disorders, Arm C
All Treated Subjects
Safety
23.05727
Listing of Adverse Event or Condition of Hypothyroidism, 
Arm C
All Treated Subjects
Safety
23.05728
Listing of Adverse Event or Condition of Ototoxicty, Arm C
All Treated Subjects
Safety
23.05729
Listing of Adverse Event or Condition of Peripheral 
Neuropathy, Arm C
All Treated Subjects
Safety
23.0580
Listing of Deaths, Arm A
All Treated Subjects
Safety
23.0590
Listing of Deaths, Arm B
All Treated Subjects
Safety
23.0600
Listing of Deaths, Arm C
All Treated Subjects
Safety
23.0610
Listing of Clinical Chemistry Data, Arm A
All Treated Subjects
Safety
23.0620
Listing of Clinical Chemistry Data, Arm B
All Treated Subjects
Safety
23.0630
Listing of Clinical Chemistry Data, Arm C
All Treated Subjects
Safety
23.0640
Listing of Hematology Data, Arm A
All Treated Subjects


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Section
Listing No.
Title
Population
Safety
23.0650
Listing of Hematology Data, Arm B
All Treated Subjects
Safety
23.0660
Listing of Hematology Data, Arm C
All Treated Subjects
Safety
23.0670
Listing of Urinalysis Data, Arm A
All Treated Subjects
Safety
23.0680
Listing of Urinalysis Data, Arm B
All Treated Subjects
Safety
23.0690
Listing of Urinalysis Data, Arm C
All Treated Subjects
Safety
23.0700
Listing of ECOG Performance Status, Arm A
All Treated Subjects
Safety
23.0710
Listing of ECOG Performance Status, Arm B
All Treated Subjects
Safety
23.0720
Listing of ECOG Performance Status, Arm C
All Treated Subjects
PK
25.0010
Listing of Derived [Analyte] [Matrix] [Primary/Secondary] 
Pharmacokinetic Parameters {by Group} 
PK
PK
25.1010
Listing of GSK3052230 Plasma Pharmacokinetic 
Concentration-Time Data, Arm A
PK
PK
25.1020
Listing of GSK3052230 Plasma Pharmacokinetic 
Concentration-Time Data, Arm B
PK
PK
25.1030
Listing of GSK3052230 Plasma Pharmacokinetic 
Concentration-Time Data, Arm C
PK
PK
25.1040
Listing of Paclitaxel Plasma Pharmacokinetic 
Concentration-Time Data, Arm A
PK
PK
25.1050
Listing of Docetaxel Plasma Pharmacokinetic 
Concentration-Time Data, Arm B
PK
PK
25.1060
Listing of Pemetrexed Plasma Pharmacokinetic 
Concentration-Time Data, Arm C
PK
20.1.11.
Other Listings
Section
Listing No.
Title
Population
Study Pop 
30.0010
Listing of Substance Use, Arm A
All Treated Subjects
Study Pop 
30.0020
Listing of Substance Use, Arm B
All Treated Subjects
Study Pop 
30.0030
Listing of Substance Use, Arm C
All Treated Subjects
Study Pop
30.0040
Listing of Current and Past Medical Conditions, Arm A
All Treated Subjects
Study Pop
30.0050
Listing of Current and Past Medical Conditions, Arm B
All Treated Subjects
Study Pop
30.0060
Listing of Current and Past Medical Conditions, Arm C
All Treated Subjects
Study Pop
30.0070
Listing of Disease Characteristics at Initial Diagnosis, 
Arm A
All Treated Subjects
Study Pop
30.0080
Listing of Disease Characteristics at Initial Diagnosis, 
Arm B
All Treated Subjects
Study Pop
30.0090
Listing of Disease Characteristics at Initial Diagnosis, 
Arm C
All Treated Subjects
Study Pop
30.0100
Listing of Disease Characteristics at Screening, Arm A
All Treated Subjects
Study Pop
30.0110
Listing of Disease Characteristics at Screening, Arm B
All Treated Subjects
Study Pop
30.0120
Listing of Disease Characteristics at Screening, Arm C
All Treated Subjects
Study Pop
30.0130
Listing of Metastatic Disease at Screening, Arm A
All Treated Subjects
Study Pop
30.0140
Listing of Metastatic Disease at Screening, Arm B
All Treated Subjects
Study Pop
30.0150
Listing of Metastatic Disease at Screening, Arm C
All Treated Subjects


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Section
Listing No.
Title
Population
Study Pop
30.0160
Listing of Prior Anti-Cancer Chemotherapy, Hormonal, 
Immunotherapy, Small Molecule Targeted Therapy, 
Radioactive Therapy and Biologic Therapy, Arm B
All Treated Subjects
Study Pop
30.0170
Listing of Prior Anti-Cancer Chemotherapy, Hormonal, 
Immunotherapy, Small Molecule Targeted Therapy, 
Radioactive Therapy and Biologic Therapy, Arm C
All Treated Subjects
Study Pop
30.0180
Listing of Prior Anti-Cancer Radiotherapy, Arm B
All Treated Subjects
Study Pop
30.0190
Listing of Prior Anti-Cancer Radiotherapy, Arm C
All Treated Subjects
Study Pop
30.0200
Listing of Prior Surgical Procedures, Arm B
All Treated Subjects
Study Pop
30.0210
Listing of Concomitant Medications, Arm A
All Treated Subjects
Study Pop
30.0220
Listing of Concomitant Medications, Arm B
All Treated Subjects
Study Pop
30.0230
Listing of Concomitant Medications, Arm C
All Treated Subjects
Study Pop
30.0240
Listing of Blood Products, Arm A
All Treated Subjects
Study Pop
30.0250
Listing of Blood Products, Arm B
All Treated Subjects
Study Pop
30.0260
Listing of Blood Products, Arm C
All Treated Subjects
Study Pop
30.0270
Listing of Blood Supportive Care Products, Arm A
All Treated Subjects
Study Pop
30.0280
Listing of Blood Supportive Care Products, Arm B
All Treated Subjects
Study Pop
30.0290
Listing of Blood Supportive Care Products, Arm C
All Treated Subjects
Efficacy
30.0300
Listing of Investigator-Assessed Lesion Assessments 
(RECIST 1.1 Criteria), Arm A
All Treated Subjects
Efficacy
30.0310
Listing of Investigator-Assessed Lesion Assessments 
(RECIST 1.1 Criteria), Arm B
All Treated Subjects
Efficacy
30.0320
Listing of Investigator-Assessed Lesion Assessments 
(RECIST 1.1 Criteria), Arm C
All Treated Subjects
Efficacy
30.0330
Listing of Investigator-Assessed Lesion Assessments 
(Modified RECIST Criteria), Arm C
All Treated Subjects
Safety
30.0340
Listing of Abnormal ECG Findings, Arm A
All Treated Subjects
Safety
30.0350
Listing of Abnormal ECG Findings, Arm B
All Treated Subjects
Safety
30.0360
Listing of Abnormal ECG Findings, Arm C
All Treated Subjects
Safety
30.0370
Listing of ECG Values, Arm A
All Treated Subjects
Safety
30.0380
Listing of ECG Values, Arm B
All Treated Subjects
Safety
30.0390
Listing of ECG Values, Arm C
All Treated Subjects
Safety
30.0400
Listing of Vital Signs, Arm A
All Treated Subjects
Safety
30.0410
Listing of Vital Signs, Arm B
All Treated Subjects
Safety
30.0420
Listing of Vital Signs, Arm C
All Treated Subjects
Safety
30.0430
Listing of Left Ventricular Ejection Fraction Results, Arm 
A
All Treated Subjects
Safety
30.0440
Listing of Left Ventricular Ejection Fraction Results, Arm 
B
All Treated Subjects
Safety
30.0450
Listing of Left Ventricular Ejection Fraction Results, Arm 
C
All Treated Subjects
Safety
30.0460
Listing of Liver Chemistry Assessments for Subjects with 
Liver Signal/Events, Arm A
All Treated Subjects
Safety
30.0470
Listing of Liver Chemistry Assessments for Subjects with 
Liver Signal/Events, Arm B
All Treated Subjects


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Section
Listing No.
Title
Population
Safety
30.0480
Listing of Liver Chemistry Assessments for Subjects with 
Liver Signal/Events, Arm C
All Treated Subjects
Safety
30.0490
Listing of Grouped Laboratory Tests and Grade -LFTs, 
Arm A
All Treated Subjects
Safety
30.0500
Listing of Grouped Laboratory Tests and Grade -LFTs, 
Arm B
All Treated Subjects
Safety
30.0510
Listing of Grouped Laboratory Tests and Grade -LFTs, 
Arm C
All Treated Subjects
Safety
30.0520
Listing of Grouped Laboratory Tests and Grade -Lipds, 
Arm A
All Treated Subjects
Safety
30.0530
Listing of Grouped Laboratory Tests and Grade -Lipds, 
Arm B
All Treated Subjects
Safety
30.0540
Listing of Grouped Laboratory Tests and Grade -Lipds, 
Arm C
All Treated Subjects
Safety
30.0550
Listing of Immunogenicity Assay Results, Arm A
All Treated Subjects
Safety
30.0560
Listing of Immunogenicity Assay Results, Arm B
All Treated Subjects
Safety
30.0570
Listing of Immunogenicity Assay Results, Arm C
All Treated Subjects
Safety
30.0580
Listing of Concurrent Actions Taken with Study 
Treatment Due to an Adverse Event, Arm A
All Treated Subjects
Safety
30.0590
Listing of Concurrent Actions Taken with Study 
Treatment Due to an Adverse Event, Arm B
All Treated Subjects
Safety
30.0600
Listing of Concurrent Actions Taken with Study 
Treatment Due to an Adverse Event, Arm C
All Treated Subjects
PD/Biomarker
26.0010
Listing of FGF2 Assay Results, Arm C
PD
PD/Biomarker
26.0020
Listing of FGF2 H-scores and Response, Arm C
PD


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20.2.
Appendix 2: Pharmacogenetics (PGx)
PGx – Background
Pharmacogenetics (PGx) is the study of variability in drug response due to hereditary 
factors in different populations. There is increasing evidence that an individual's genetic 
composition (i.e., genotype) may impact the pharmacokinetics (PK) (absorption, 
distribution, metabolism, and elimination), pharmacodynamics (PD) (relationship 
between concentrations and pharmacologic effects or the time course of pharmacologic 
effects) and/or clinical outcome (in terms of efficacy and/or safety and tolerability). Some 
reported examples of PGx associations with safety/adverse events include:
Drug
Disease
Gene
Outcome
Abacavir
HIV
[Hetherington, 2002; 
Mallal, 2002]
Human 
Leukocyte 
Antigen B (HLA-
B*5701)
Individuals with HLA-B*5701 variant may be at 
increased risk for experiencing hypersensitivity to 
abacavir. Clinical assays are available for HLA-B*5701 
but none has been validated. HLA-B*5701 screening 
would supplement but never replace abacavir clinical 
risk management strategies aimed at minimizing rare 
but serious outcomes associated with abacavir 
hypersensitivity
Carbamazepine
Seizure, Bipolar 
disorders & 
Analgesia 
Chung, 2010; 
Ferrell, 2008.
HLA-B*1502
Independent studies indicated that patients of East 
Asian ancestry who carry HLA-B*1502 are at higher risk 
of Stevens-Johnson Syndrome and toxic epidermal 
necrolysis. Regulators, including the US FDA and the 
Taiwanese TFDA, have updated the carbamazepine 
drug label to indicate that patients with ancestry in 
genetically at risk populations should be screened for 
the presence of HLA-B*1502 prior to initiating treatment 
with carbamazepine.
Warfarin
Cardiovascular
[Neergard, 2006;
Wilke, 2005]
CYP2C9
SAEs experienced by some subjects on warfarin may 
be explained by variations in the CYP2C9 gene that 
influences the degree of anticoagulation achieved.
Irinotecan
Cancer
FDA News Release, 
2005
UGT1A1
Variations in the UGT1A1 gene can influence a 
patient’s ability to break down irinotecan, which can 
lead to increased blood levels of the drug and a higher 
risk of side effects. A dose of irinotecan that is safe for 
one patient with a particular UGT1A1 gene variation 
might be too high for another subject without this 
variation, raising the risk of certain side effectsA genetic 
blood test (Invader UGT1A1molecular assay) is 
available that can detect variations in the gene.
A key component to successful PGx research is the collection of samples during the 
conduct of clinical studies.
Collection of whole blood, may enable PGx analysis to be conducted if at any time it 
appears that there is a potential unexpected or unexplained variation in handling or 
response to GSK3052230.


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PGx Research Objectives
The objective of the PGx research (if there is a potential unexpected or unexplained 
variation) is to investigate a possible genetic relationship to handling or response to 
GSK3052230. If at any time it appears there is potential variability in response in this 
clinical study or in a series of clinical studies with GSK3052230 that may be attributable 
to genetic variations of subjects, the following objectives may be investigated:

Relationship between genetic variants and the PK and/or PD of study treatment

Relationship between genetic variants and safety and/or tolerability of study 
treatment

Relationship between genetic variants and efficacy of study treatment.
Study Population
Any subject who has given informed consent to participate in the clinical study, has met 
all the entry criteria for the clinical study, and receives study treatment may take part in 
the PGx research. Any subject who has received an allogeneic bone marrow transplant 
must be excluded from the PGx research.
Subject participation in the PGx 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.
Study Assessments and Procedures
In addition to any blood samples taken for the clinical study, a whole blood sample 
(~6 mL) will be collected for the PGx research using a tube containing EDTA. It is 
recommended that the blood sample be taken at the first opportunity after a subject has 
been randomized and provided informed consent for PGx research, but may be taken at 
any time while the subject is participating in the clinical study.
The PGx sample is labeled (or “coded”) with a study specific number that can be traced 
or linked back to the subject only by the investigator or site staff. Coded samples do not 
carry personal identifiers (such as name or social security number). The blood sample is 
taken on a single occasion unless a duplicate sample is required due to inability to utilize 
the original sample. 
The DNA extracted from the blood sample may be subjected to sample quality control 
analysis. This analysis will involve the genotyping of several genetic markers to confirm 
the integrity of individual samples. If inconsistencies are noted in the analysis, then those 
samples may be destroyed. 
The need to conduct PGx analysis may be identified after a study (or set of studies) of 
GSK3052230 has been completed and the study data reviewed. In some cases, the 
samples may not be studied. e.g., no questions are raised about how people respond to 
GSK3052230. 


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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 use samples collected from the study for the 
purpose stated in this protocol and in the informed consent form. 
Subjects can request their sample to be destroyed at any time.
Subject Withdrawal from Study
If a subject who has consented to participate in PGx research and has a sample taken for 
PGx research withdraws from the clinical study for any reason other than lost to follow-
up, the subject will be given the following options:

The sample is retained for PGx research.

Any PGx sample is destroyed.
If a subject withdraws consent from the PGx 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. In either case, GSK will only keep study 
information collected/generated up to that point.
Screen and Baseline Failures
If a blood sample for PGx research has been collected and it is determined that the 
subject does not meet the entry criteria for participation in the clinical study, then 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.
PGx Analyses
The aim of pharmacogenetic analyses will be to investigate the relationship between 
genetic variations in germline DNA and response to study treatment. The specific type of 
genetic investigation to be applied will be dependent on the most scientifically feasible 
approach available to address understanding of the response to the study treatment.
Generally, two approaches may be utilized to explore the association of genetic variation.
3.
Candidate gene analysis where variations in specific genes may be studied that 
encode the drug target, or drug mechanism of action pathways, drug metabolizing 
enzymes, drug transporters or which may underpin adverse events, disease risk or 
drug response.
These candidate genes that may be investigated in this study include the following: the 
GSK Absorption, Distribution, Metabolism and Excretion genes. These play a central 
role in drug PK and PD.  In addition, continuing research may identify other enzymes, 
transporters, proteins, or receptors that may be involved in response to GSK3052230. The 
genes that may code for these proteins may also be studied.


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4.
Genome-wide scans involving a large number of polymorphic markers (e.g., single 
nucleotide polymorphisms) located throughout the genome. This approach is often 
employed when potential genetic effects are not well understood.
The results of PGx investigations will be reported either as part of the main clinical study 
report or as a separate report. All endpoints of interest from all comparisons will be 
descriptively and/or graphically summarized as appropriate to the data. In all cases, 
appropriate statistical methods will be used to analyze the genetic markers in the context 
of other clinical data. Statistical methods may include, but are not limited to Hardy-
Weinberg Equilibrium testing, Comparison of Demographic and Baseline Characteristics 
by Genotype, Evaluation of Genotypic Effects, Evaluation of Treatment by Genotype and 
Gene-Gene Interaction, Linkage Disequilibrium, Multiple Comparison and Multiplicity 
and/or Power and Sample Size Considerations A detailed description of the analyses to 
be performed will be documented in the pharmacogenetics RAP.
Informed Consent
Subjects who do not wish to participate in the PGx research may still participate in the 
clinical study. PGx informed consent must be obtained prior to any blood being taken for 
PGx research.
Provision of Study Results and Confidentiality of Subject’s PGx Data
GSK may summarize the cumulative PGx research results in the clinical study report,.
In general, GSK does not inform the investigator, subject or anyone else (e.g., family 
members, study investigators, primary care physicians, insurers, or employers) of the 
PGx research results unless required by law. The information generated from PGx 
research is preliminary in nature, and the significance and scientific validity of the results 
are undetermined at such an early stage of research. 
References
Chung WH, Hung SL, Chen YT. Genetic predisposition of life-threatening antiepileptic-
induced skin reactions. Expert Opin. Drug Saf. 2010; 9: 15-21.
Ferrell PB, McLeod HL. Carbamazepine, HLA-B*1502 and risk of Stevens-Johnson 
syndrome and toxic epidermal necrolysis: US FDA recommendations. 
Pharmacogenomics. 2008; 9: 1543-46.
Hetherington S, Hughes AR, Mosteller M, Shortino D, Baker KL, Spreen W, Lai E, 
Davies K, Handley A, Dow DJ, Fling ME, Stocum M, Bowman C, Thurmond LM, Roses 
AD. Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. 
Lancet. 2002; 359:1121-2.
Mallal S, Nolan D, Witt C, Masel G, Martin AM, Moore C, Sayer D, Castley A, Mamotte 
C, Maxwell D, James I. Association between presence of HLA-B*5701, HLA-DR7, and 
HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet. 
2002; 359:727-32.


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Neergard. Reducing the risk of blood thinners. Associated press, September 2006. 
U.S. Food and Drug Administration, FDA Clears Genetic Test That Advances 
Personalized Medicine Test Helps Determine Safety of Drug Therapy 22 August 2005, 
http://www.fda.gov/bbs/topics/NEWS/2005/NEW01220.html
Wilke RA, Musana AK, Weber WW. Cytochrome P450 gene-based drug prescribing, 
and factors impacting translation into routine clinical practice. Personalized Med 2005; 2: 
213–224.