Clinical trial NCT05553808
Conditions: Neoplasms
Sponsor: GlaxoSmithKline
Start date: 2019-01-24; Completion date: 2021-09-23
Enrollment: 105 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study is a sub-study of the master protocol 205801 (NCT03739710). This sub study has assessed the clinical activity of novel regimen (Feladilimab plus Docetaxel) with SOC (Docetaxel) in participants with NSCLC.

Detailed description:

Arms: arm 1: None arm 2: None
Interventions: intervention 1: Docetaxel intervention 2: Feladilimab
Intervention descriptions: intervention 1: Docetaxel was administered as IV infusion. intervention 2: Feladilimab was administered as IV infusion.

Protocol documents:
Prot_000.pdf: 
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TITLE PAGE 
Protocol Title: A Phase II, Randomized, Open-label Platform Trial Utilizing a Master 
Protocol to Study Novel Regimens Versus Standard of Care Treatment in NSCLC 
Participants 
Protocol Number: 205801/Amendment 08 
Short Title: Phase II NSCLC Master Protocol 
Compound Number: GSK4428859A 
Study Phase: II 
Sponsor Name and Legal Registered Address:  
GlaxoSmithKline Research & Development Limited 
980 Great West Road 
Brentford 
Middlesex, TW8 9GS 
UK 
Regulatory Agency Identifying Number(s):  
IND Number: 138944 
EudraCT Number: 2018-001316-29  
 
Sponsor Signatory: 
Sumita Roy-Ghanta, MD 
Clinical Development Lead, 
Oncology Research & Development 
GlaxoSmithKline 
 
Approval Date: 23 May 2022 
 
 
 
 
© 2022 the GlaxoSmithKline group of companies. All rights reserved. Unauthorized 
copying or use of this information is prohibited 
 


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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
DNG or TMF Number 
Amendment 8 
23 May 2022 
TMF-14611949 
Amendment 7 
08-Mar-2022 
TMF- 14511980 
Amendment 6 
19-Nov-2021 
TMF-14000899 
Amendment 5 
02-Sep-2021 
TMF-13833961 
Amendment 4 
02-Feb-2021 
TMF-11698443 
Amendment 3 
29-Oct-2020 
2017N337080_03 
Amendment 2 
15-Jul-2019 
2017N337080_02 
Amendment 1 
20-Sep-2018 
2017N337080_01 
Original Protocol 
23-Jul-2018 
2017N337080_00 
 
Amendment 8: 23 May 2022 
Protocol Amendment Summary of Changes Tables are provided in Section 12.1.4 and 
Section 12.1.5. 
Overall Rationale for the Amendment: The protocol has been amended to include 
additional safety assessments for cardiac monitoring in the Schedule of Activities under 
Section 12.1 (sub Section 12.1.4 and Section 12.1.5). More specifically, the additional 
assessments introduced in the Schedule of Activities for Arms 4 and 5 are:  
• Clarification provided for troponin assessment, Troponin I to be preferred over 
Troponin T and high sensitivity assays to be preferred where available  
• BNP (NT-pro-BNP preferred), to be included as a safety laboratory assessment at 
screening, each dosing visit (Q3W) and treatment discontinuation visit 
• Recommendation for cardiology consultation for clinically significant: i) ECG 
abnormalities and/ or ii) troponin/ BNP elevations. The Investigator/ cardiologist 
should consider investigations as per current practice guidelines to exclude 
myocarditis and evaluate other causes as clinically indicated. This should 
preferably include imaging e.g., cardiac MRI and/or Echocardiogram. 
Changes in the Dose Modification and Management guidelines reflect the changes in the 
SoA. 
 
 


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TABLE OF CONTENTS 
PAGE 
TITLE PAGE ................................................................................................................... 1 
TABLE OF CONTENTS .................................................................................................. 3 
1. 
SYNOPSIS ............................................................................................................... 7 
2. 
SCHEDULE OF ACTIVITIES (SOA) ....................................................................... 10 
3. 
INTRODUCTION .................................................................................................... 11 
3.1. 
Study Rationale .......................................................................................... 11 
3.2. 
Background ................................................................................................ 11 
3.3. 
Benefit/Risk Assessment ............................................................................ 12 
3.4. 
Overall Benefit-Risk Conclusion .................................................................. 13 
4. 
OBJECTIVES AND ENDPOINTS ........................................................................... 13 
4.1. 
Objectives and Endpoints: Part 1 ................................................................ 13 
4.2. 
Objectives and Endpoints: Part 2 ................................................................ 13 
5. 
STUDY DESIGN .................................................................................................... 15 
5.1. 
Overall Design ............................................................................................ 15 
5.2. 
Duration of Treatment ................................................................................. 18 
5.3. 
Number of Participants ............................................................................... 18 
5.3.1. 
Sample Size: Part 1 ..................................................................... 18 
5.3.2. 
Sample Size: Part 2 ..................................................................... 19 
5.4. 
Participant Completion and End of Study Definitions .................................. 19 
5.4.1. 
Participant Completion Definitions ............................................... 19 
5.4.2. 
Study Completion Definition ......................................................... 19 
5.5. 
Scientific Rationale for Study Design .......................................................... 19 
5.5.1. 
Steering Committee and Data Monitoring Committee (Part 
2) ................................................................................................. 20 
5.6. 
Dose Justification ........................................................................................ 20 
6. 
STUDY POPULATION ........................................................................................... 21 
6.1. 
Inclusion Criteria ......................................................................................... 21 
6.2. 
Exclusion Criteria ........................................................................................ 24 
6.3. 
Lifestyle and Dietary Restrictions ................................................................ 27 
6.4. 
Screen Failures........................................................................................... 27 
6.5. 
Screening under Molecular Disease Characterization Initiative 
Study .......................................................................................................... 28 
7. 
TREATMENTS ....................................................................................................... 28 
7.1. 
Treatments Administered ............................................................................ 28 
7.2. 
Dose Modification ....................................................................................... 29 
7.2.1. 
Dose and Safety Management Guidelines ................................... 29 
7.3. 
Method of Treatment Assignment ............................................................... 32 
7.4. 
Blinding ....................................................................................................... 32 
7.5. 
Preparation/Handling/Storage/Accountability .............................................. 32 
7.5.1. 
Preparation .................................................................................. 32 


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7.5.2. 
Handling ...................................................................................... 33 
7.5.3. 
Storage ........................................................................................ 33 
7.5.4. 
Accountability .............................................................................. 33 
7.6. 
Treatment Compliance ................................................................................ 33 
7.7. 
Concomitant Therapy.................................................................................. 34 
7.7.1. 
Permitted Medications and Non-Drug Therapies .......................... 34 
7.7.2. 
Prohibited Medications and Non-Drug Therapies ......................... 35 
7.8. 
Treatment after the End of the Study .......................................................... 35 
8. 
DISCONTINUATION CRITERIA ............................................................................. 35 
8.1. 
Discontinuation of Study Treatment ............................................................ 35 
8.1.1. 
Liver Chemistry Stopping Criteria ................................................ 37 
8.1.2. 
Study Treatment Restart/Rechallenge ......................................... 40 
8.2. 
Withdrawal from the Study .......................................................................... 40 
8.3. 
Lost to Follow-up ........................................................................................ 41 
9. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 41 
9.1. 
General Guidance ....................................................................................... 41 
9.1.1. 
General Guidance for Treatment Continuity when 
Participants are Unable to Come into the Clinic ........................... 42 
9.2. 
Screening and Critical Baseline Assessments ............................................ 43 
9.3. 
Efficacy Assessments ................................................................................. 44 
9.3.1. 
Tumor Imaging and Disease Assessments .................................. 45 
9.3.2. 
Tumor Growth Kinetics ................................................................ 47 
9.3.3. 
Survival Follow-up ....................................................................... 47 
9.4. 
Adverse Events........................................................................................... 47 
9.4.1. 
Time Period and Frequency for Collecting AE and SAE 
Information ................................................................................... 47 
9.4.2. 
Method of Detecting AEs and SAEs ............................................. 48 
9.4.3. 
Follow-up of AEs and SAEs ......................................................... 48 
9.4.4. 
Regulatory Reporting Requirements for SAEs ............................. 48 
9.4.5. 
Cardiovascular and Death Events ................................................ 49 
9.4.6. 
Pregnancy ................................................................................... 49 
9.5. 
Safety Assessments ................................................................................... 49 
9.5.1. 
Physical Examinations ................................................................. 50 
9.5.2. 
Performance Status ..................................................................... 50 
9.5.3. 
Vital Signs .................................................................................... 50 
9.5.4. 
Electrocardiograms ...................................................................... 50 
9.5.5. 
Echocardiogram........................................................................... 51 
9.5.6. 
Clinical Safety Laboratory Assessments ...................................... 51 
9.6. 
Pharmacokinetics ....................................................................................... 52 
9.6.1. 
Blood Sample Collection .............................................................. 52 
9.6.2. 
Sample Analysis .......................................................................... 52 
9.7. 
Anti-Drug Antibodies ................................................................................... 52 
9.8. 
Genetics ..................................................................................................... 52 
9.9. 
Biomarkers ................................................................................................. 53 
9.9.1. 
Blood Biomarkers ........................................................................ 53 
9.9.2. 
Tumor Tissue ............................................................................... 53 
9.10. 
Patient-Reported Outcome Assessments ................................................... 54 
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10. STATISTICAL CONSIDERATIONS ........................................................................ 58 
10.1. 
Primary Endpoint ........................................................................................ 58 
10.1.1. 
Primary Endpoint: Part 1 .............................................................. 58 
10.1.2. 
Primary Endpoint: Part 2 .............................................................. 58 
10.2. 
Hypothesis .................................................................................................. 59 
10.2.1. 
Hypothesis: Part 1 ....................................................................... 59 
10.2.2. 
Hypothesis: Part 2 ....................................................................... 59 
10.3. 
Sample Size Determination ........................................................................ 59 
10.3.1. 
Sample Size: Part 1 ..................................................................... 59 
10.3.2. 
Sample Size: Part 2 ..................................................................... 61 
10.3.3. 
Interim Analyses .......................................................................... 62 
10.3.4. 
Statistical Operating Characteristics ............................................ 64 
10.3.5. 
Sample Size Sensitivity ................................................................ 66 
10.3.6. 
Sample Size Re-estimation .......................................................... 68 
10.4. 
Populations for Analyses ............................................................................ 68 
10.5. 
Statistical Analyses ..................................................................................... 69 
10.5.1. 
Analysis ....................................................................................... 69 
10.5.2. 
Other Secondary Analyses .......................................................... 70 
10.5.3. 
Safety Analyses ........................................................................... 71 
10.5.4. 
Pharmacokinetic Analyses ........................................................... 71 
10.5.5. 
Pharmacokinetic/Pharmacodynamic Analyses ............................. 72 
10.5.6. 
Tumor Kinetic Analyses ............................................................... 72 
10.5.7. 
Other Analyses ............................................................................ 72 
11. REFERENCES ....................................................................................................... 73 
12. APPENDICES ........................................................................................................ 79 
12.1. 
Appendix 1: Arms ....................................................................................... 79 
12.1.1. 
Standard of Care Arm 1: Docetaxel Alone (Part 2 ONLY) ............ 79 
12.1.2. 
Substudy 1 (Arm 2): Feladilimab and Docetaxel 
Combination ................................................................................ 92 
12.1.3. 
Arm 3: Feladilimab and Ipilimumab Combination ....................... 109 
12.1.4. 
Arm 4: GSK4428859A (Anti-TIGIT) and Dostarlimab (Anti-
PD-1) Combination .................................................................... 146 
12.1.5. 
Arm 5: GSK4428859A (Anti-TIGIT) plus Dostarlimab (Anti-
PD-1) plus GSK6097608 (Anti-CD96) Combination ................... 193 
12.2. 
Appendix 2: Abbreviations and Trademarks .............................................. 247 
12.3. 
Appendix 3: Clinical Laboratory Tests ....................................................... 251 
12.4. 
Appendix 4: Study Governance Considerations ........................................ 252 
12.5. 
Appendix 5: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting ..................................... 256 
12.6. 
Appendix 6: Contraceptive Guidance and Collection of Pregnancy 
Information ................................................................................................ 262 
12.7. 
Appendix 7: Genetics ................................................................................ 266 
12.8. 
Appendix 8: ECOG Performance Status ................................................... 267 
12.9. 
Appendix 9: CKD-EPI and Cockcroft-Gault Formulas ............................... 268 
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12.10. Appendix 10: Liver Safety: Required Actions and Follow-up 
Assessments and Study Treatment Rechallenge Guidelines .................... 270 
12.10.1. For Participants with ALT up to 2.5 X ULN at Baseline: ............. 270 
12.10.2. For Participants with Documented Liver Metastases and 
ALT up to 5 X ULN at Baseline: ................................................. 272 
12.10.3. Phase II Liver Chemistry Increased Monitoring Criteria 
with Continued Therapy ............................................................. 274 
12.10.4. Liver Safety Drug Restart or Rechallenge Guidelines ................ 275 
12.11. Appendix 11: Country-Specific Requirements ........................................... 278 
12.12. Appendix 12: Guidelines for Assessment of Disease, Disease 
Progression and Response Criteria .......................................................... 279 
12.12.1. RECIST 1.1 Guidelines .............................................................. 279 
12.12.2. iRECIST Guidelines ................................................................... 284 
12.13. Appendix 13: Supplemental Statistical Information ................................... 290 
12.13.1. Parameters for Piecewise Weibull Distribution ........................... 290 
12.13.2. Calculation of PoS of Phase 3 Given Data from Phase 2 ........... 290 
12.14. Appendix 14: Immune-Related Diseases .................................................. 296 
12.15. Appendix 15: Protocol Amendment History ............................................... 298 
 
 


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1. 
SYNOPSIS 
Protocol Title: A Phase II, Randomized, Open-label Platform Trial Utilizing a Master 
Protocol to Study Novel Regimens Versus Standard of Care Treatment in NSCLC 
Participants  
Short Title: Phase II NSCLC Master Protocol  
Rationale: 
Study 205801 is a randomized, Phase II open-label platform trial in two parts utilizing a 
master protocol to investigate the clinical activity of novel regimens compared with 
standard of care (SoC) regimens in participants with relapsed/refractory advanced non-
small cell lung cancer (NSCLC) who have prior platinum-containing chemotherapy 
regimen and an immuno-oncology agent treatment failure, such as anti-programmed cell 
death protein 1 [PD1] / PD-Ligand 1 [PD-L1] – either in combination or as separate lines. 
NSCLC is considered intrinsically resistant to immuno-oncology agents owing in part to 
its broad immune escape and suppressive features that include low antigenicity, despite 
having one of the highest frequencies of somatic mutations, and a high presence of 
regulatory T cells (Tregs). However, as shown by the single-agent response rates of anti-
PD-1 inhibitors in NSCLC, a subset of tumors are susceptible to T cell-mediated 
antitumor effects, suggesting those tumors have some degree of prior T-cell immunity. 
Since effective anticancer immune response involves stepwise multistep processes, lung 
cancers may possess or acquire features that enable them to evade immune surveillance, 
suppress immune reactivity, proliferate, and survive within an inflammatory 
microenvironment, thereby rendering an immune response ineffectual. Therefore, 
treatment modalities that incorporate combinations with agents targeting different 
processes within the immune cascade have the potential to reinstate immunosurveillance; 
these may include regimens containing chemotherapy that possess advantageous 
immunological effects to potentially improve clinical efficacy. 
Objectives and Endpoints (Part 1) 
Objectives 
Endpoints 
Primary 
To determine the safety and tolerability of novel 
regimen(s) 
AEs, SAEs, DLTs, changes in safety/laboratory 
assessment parameters, dose modifications 
Secondary 
To provide a preliminary evaluation of the efficacy of 
experimental regimen(s) 
Objective Response Rate (ORR) 
Disease Control Rate (DCR) 
Characterize the pharmacokinetic properties 
of experimental regimen(s) 
PK parameters that include Cmax and Cmin for 
experimental regimen(s) (and investigational agent/s 
included in other arms), as data permit. 
 


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Objectives and Endpoints (Part 2): 
Objectives 
Endpoints 
Primary 
Determine whether experimental regimen(s) 
provide evidence for improved survival over 
SoC therapy 
Overall survival as measured by time from randomization to death 
Secondary 
Evaluate milestone survival in participants 
treated with experimental regimen(s) versus 
SoC therapy for NSCLC 
Milestone survival rate at 12 and 18 months  
Evaluate other measures of antitumor 
activity of the experimental regimen(s) 
compared with SoC therapy for NSCLC 
(RECIST 1.1 and iRECIST) 
CR, PR, SD, PD, PFS, ORR, DOR, DCR 
iCR, iPR, iUPD, iCPD, iSD 
iPFS; iORR; iDOR 
Evaluate the safety and tolerability of the 
experimental regimen(s) compared with 
SoC therapy for NSCLC 
 
Frequency and severity of AEs, AESI; SAEs and AE/SAEs leading to 
dose modifications/delays/withdrawals; changes in laboratory, vital 
signs, and safety assessment parameters, including immunogenicity 
(ADA) 
Characterize the pharmacokinetic properties 
SoC or experimental regimen(s) 
PK parameters that may include Cmax and Cmin for experimental 
regimen(s) and for SoC alone, as data permit. 
Determine immunogenicity of experimental 
regimen(s) 
ADA incidence for experimental regimen(s)  (where appropriate) 
Note: The prefix “i”, used for response related abbreviations in the above table indicates immune responses assigned 
using iRECIST. 
ADA= anti-drug antibody; AE = adverse event/s; AESI = adverse event/s of special interest; Cmax = maximum 
concentration; Cmin = minimum concentration; CPD = confirmed progression; CR = complete response; DLT = Dose 
Limiting Toxicity’ DOR = duration of response; NSCLC = non-small cell lung cancer; ORR = objective response rate; 
OS = overall survival; PD = progressive disease; PFS = progression-free survival; PR = partial response; RECIST = 
Response Evaluation Criteria In Solid Tumors; SAE = serious adverse event; SD = stable disease; SoC = standard of 
care; UPD = unconfirmed progression. 
 
Overall Design: 
This is a randomized Phase II, open-label, platform trial utilizing a master protocol 
designed to study novel immunotherapy drug combinations compared with the current 
SoC, in the treatment of patients with advanced NSCLC who have progressed on prior 
anti-PD(L)1 and platinum-based combination chemotherapies. The study will initially 
evaluate 2 treatment regimens/arms, with additional regimens/arms added via protocol 
amendment(s) (see the Study Design schematic below).  
The study will be conducted in two parts; Part 1 is an open-label, optional, non-
randomized part based on safety and pharmacokinetics/pharmacodynamics (PK/PD) 
evaluation. Part 2 is a randomized, Phase II, open-label part comparing the efficacy and 
safety of these novel regimens with SoC. Part 2, is structured as a series of substudies that 
share a common control arm with ongoing updating of the effect size of the control arm 
through the addition of new participants with each substudy. Each combination will be 
first evaluated in a separate study/arm for safety. This evaluation may occur prior to 
adoption into 205801 platform study (dose finding in a separate study) or as a distinct 
arm within this platform study (Part 1) prior to Part 2. If an experimental regimen meets 
graduation requirements, i.e., passes criteria for safety and preliminary clinical activity, 
they may advance to Part 2. Graduation will be the term used throughout the protocol to 


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refer to the advancement of a combination from Part 1 to Part 2. As a clarification, the 
combination will be tested in a new population that will be randomized between the 
combination and the Standard of Care. The study participants enrolled in Part 1 are not 
pooled with the study participants in Part 2. The two study populations are separate and 
distinct. Part 1 is open label single arm while Part 2 is randomized.  
For the randomized survival evaluation, participants will be stratified by histology 
(squamous vs. non-squamous) and line of PD(L)1 therapy (1st vs. 2nd line). Patients with 
NSCLC with undetermined histology (i.e. NSCLC not otherwise specified) will be 
considered as non-squamous for stratification purposes. 
Each additional treatment arm/regimen will be analyzed relative to the SoC treatment and 
is considered a substudy within the overall master protocol, as depicted below.  
Study Design 
 
 
NSCLC: non-small cell lung cancer; PD(L)1: Programmed Cell Death Protein 1 or Programmed Cell Death Ligand 1.  
Note: Randomization of participants to experimental treatment regimens/arms may not occur in parallel. It should 
also be noted that the terms ‘regimen’ and ‘arm’ may be used interchangeably throughout the document. 
Number of Participants: 
As the study uses a master protocol design, the sample size is not fixed.  
For Part 1, sample size will be defined for each regimen under the corresponding 
appendix in Section 12.1; a minimum of 3 participants will be evaluated for safety before 
further participants will be enrolled. 


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The initial number of participants for Part 2 in substudy 1 is estimated to be at least 105 
(SoC arm: 35; experimental arm: 70 for substudy 1). Additional substudies and their 
corresponding experimental regimens will be added via protocol amendments. Each 
additional experimental arm will enroll a maximum of 70 participants. Randomization to 
SoC/Arm 1 will be minimized through an alteration of the randomization ratio once 35 
participants are randomized to that arm.  
Treatment Groups and Duration: 
Study participation begins with the signing of the informed consent form (ICF) within 
45 days prior to the first dose. After a screening period of up to 28 days, eligible 
participants will be assigned a treatment arm if participating in Part 1 and receive study 
treatment (Day 1), or randomly assigned to a treatment arm (SoC or experimental) if 
participating in Part 2 and receive study treatment (Day 1).  
Unless otherwise specified in the treatment-specific appendix, investigational 
combination study treatment will continue at the indicated schedule for a maximum 
duration of approximately 2 years or up to 35 treatment visits, whichever comes first, or 
until disease progression, death, unacceptable toxicity, or withdrawal of consent. Single 
agent SoC treatment (i.e. docetaxel) may continue until disease progression, death, 
unacceptable toxicity, withdrawal of consent, or per institutional standard for docetaxel. 
After the study treatment is permanently discontinued, participants will be followed, via 
telephone contact, for survival and subsequent anticancer therapy every 12 weeks until 
death or the participant’s withdrawal from further contact. Participants permanently 
discontinuing study treatment prior to documented disease progression by iRECIST will 
also be followed every 12 weeks for disease progression or participant’s withdrawal from 
further contact. 
The study will be considered ‘finished’ once the last participant from all open treatment 
arms has completed their last survival follow-up contact. 
2. 
SCHEDULE OF ACTIVITIES (SoA) 
The Schedules of Activities can be found in the corresponding appendix for each 
arm in Section 12.1.  
• The timing and number of planned study assessments, including safety, 
pharmacokinetic, pharmacodynamic/biomarker or other assessments may be 
altered during the course of the study based on newly available data (e.g., to 
obtain data closer to the time of peak plasma concentrations) to ensure appropriate 
monitoring.  
• Any changes in the timing or addition of time points for any planned study 
assessments must be documented and approved by the relevant study team 
member and then archived in the sponsor and site study files but will not 
constitute a protocol amendment. The Institutional review board/ Independent 
ethics committees (IRB/IEC) will be informed of any safety issues that require 
alteration of the safety monitoring scheme or amendment of the Informed consent 
form (ICF). 


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3. 
INTRODUCTION 
Study 205801 is an open-label platform trial utilizing a master protocol designed to 
investigate the clinical activity of novel regimens compared with standard of care (SoC) 
regimen in participants with relapsed/refractory advanced non-small cell lung cancer 
(NSCLC) who have prior platinum-containing regimen and anti‑programmed cell death 
protein 1 [PD‑1] / PD-Ligand 1 [PD-L1] treatment failure. The study will be conducted in 
two parts; Part 1 is an optional, non-randomized part based on safety and 
pharmacokinetics/pharmacodynamics (PK/PD) evaluation. Part 2 is a randomized, Phase 
II part comparing the efficacy and safety of these novel regimens with SoC. 
3.1. 
Study Rationale 
While a subset of NSCLC tumors are responsive to immuno-oncology agents, a sizable 
portion of NSCLC tumors is considered to be intrinsically resistant to immuno-oncology 
agents, owing in part to its broad immune escape and suppressive features that include 
low antigenicity, despite having one of the highest frequencies of somatic mutations 
[Lawrence, 2013], and a high presence of regulatory T cells (Tregs). However, as shown 
by the single-agent response rates of anti-PD-1 inhibitors in NSCLC, a subset of tumors 
are susceptible to T cell-mediated antitumor effects, suggesting those tumors have some 
degree of prior T-cell immunity [Brahmer, 2015; Rittmeyer, 2017; Reck, 2016]. Since 
effective anticancer immune response involves stepwise multistep processes [Chen, 
2013], lung cancers may possess or acquire features that enable them to evade immune 
surveillance, suppress immune reactivity, proliferate, and survive within an inflammatory 
microenvironment thereby rendering an immune response ineffectual. Therefore, 
treatment modalities that incorporate combinations with agents targeting different 
processes within the immune cascade have the potential to reinstate immunosurveillance; 
these may include regimens containing chemotherapy that possess advantageous 
immunological effects to improve clinical efficacy [Galluzzi, 2015].  
3.2. 
Background 
Cancer is one of the leading causes of death worldwide, accounting for 8.8 million deaths 
in 2015. Lung cancer is the most common cause of cancer death, accounting for 
1.69 million deaths worldwide [Cancer Fact Sheet, 2017]. Globally, the incidence and 
mortality rates attributed to cancer vary across regions; nevertheless, lung cancer remains 
the leading cause of cancer death in men and the second leading cause of cancer death in 
women [Torre, 2015]. Non-small cell lung cancer accounts for the vast majority of lung 
cancer cases (up to 85%), with disease stage, histological subtype (e.g., adenocarcinoma, 
squamous, large cell, etc.), and molecular features playing a principal role in making 
treatment choices. In advanced-stage metastatic NSCLC positive for a specific molecular 
alteration (i.e., EGFR/ALK/ROS/BRAF), targeted single-agent approaches are 
recommended [NCCN, 2021; Planchard, 2018; Postmus, 2017]. In metastatic non-
squamous NSCLC, the first-line option for some patients is the approved triplet regimen 
consisting of pembrolizumab (an anti-PD-1 inhibitor) added to the 
pemetrexed/carboplatin backbone [Langer, 2016; KEYTRUDA, 2018]. An alternative 
current standard for NSCLC (squamous or non-squamous) is pembrolizumab as a single-
agent for (a) first-line treatment of metastatic NSCLC patients whose tumors have high 


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PD-L1 expression (Tumor Proportion Score [TPS] ≥50%) or, (b) in subsequent lines 
(post-platinum) of treatment of patients with metastatic NSCLC (squamous or non-
squamous) whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved 
test [Reck, 2016; KEYTRUDA, 2018]. Additional subsequent-line treatment options 
include other single-agent anti-PD-1/PD-L1 inhibitors (e.g., nivolumab and 
atezolizumab) if not administered as first-line [Brahmer, 2015; Rittmeyer, 2017]. In 
patients with advanced or metastatic non-squamous NSCLC without EGFR/ALK 
alternations and with PD-L1 TPS ≥1%, more durable responses were observed with 
pembrolizumab monotherapy compared to platinum-based chemotherapy alone, and 
support pembrolizumab as a standard first-line treatment option for all PD-L1-positive 
cancers [Lopes, 2016]. Additionally, in patients with previously untreated metastatic 
squamous NSCLC, the addition of pembrolizumab to platinum-based chemotherapy 
show significant improved survival regardless of PD-L1 expression level, and may be 
considered as a standard first-line treatment for metastatic squamous NSCLC regardless 
of PD-L1 status [Paz-Ares, 2018]. Recently, ESMO clinical practice guidelines have been 
updated to include the addition of atezolizumab to first-line chemotherapy in the 
metastatic non-small cell lung cancer setting [Planchard, 2018]. Single-agent 
chemotherapy such as pemetrexed for non-squamous NSCLC (if not used as part of the 
platinum-containing chemotherapy regimen earlier) or gemcitabine for squamous 
NSCLC or docetaxel for all NSCLC sub-types have been relegated to later lines and can 
be selected based on the patient’s treatment history, disease characteristics, and 
performance status.  
Docetaxel is approved by the US FDA and EMA as a single-agent for patients with 
locally advanced or metastatic NSCLC after platinum-based chemotherapy [TAXOTERE 
PI, 2020 and TAXOTERE SmPC 2020]. With the recent approvals of nivolumab in the 
same line of therapy, i.e., after progression on platinum-based doublet [OPDIVO PI, 
2018], docetaxel has been relegated to the status of a subsequent therapy, as noted in the 
ESMO/NCCN guidelines [Herbst, 2016; Horn, 2017; Novello, 2016; NCCN, 2019]. The 
clinical activity of older single-agent chemotherapies such as docetaxel as second-line 
treatment in NSCLC is limited with response rates in the range of 9 to 24% [Shepherd, 
2000; Hanna, 2004]. 
Patients with NSCLC that has failed both a platinum-containing chemotherapy regimen 
and an anti-PD(L)1 inhibitor (used either in combination or as separate lines of therapy) 
have a high unmet medical need for treatment advances with the potential to improve 
progression-free survival (PFS) and overall survival (OS). 
3.3. 
Benefit/Risk Assessment 
Benefits and risks for each combination partner can be found in the respective 
subsections under Section 12.1. Detailed information related to the known and expected 
benefits and risks including expected AEs of each experimental agent may be found in 
the corresponding Investigator’s Brochure (IB). Refer to the latest docetaxel product 
labels [TAXOTERE PI, 2020; TAXOTERE SmPC, 2020] for information on 
contraindications, warnings, and precautions related to the use of docetaxel. 
 


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3.4. 
Overall Benefit-Risk Conclusion 
There is biologic rationale to study these novel combinations in this setting based on 
complementary modes of action on the immune system, with the potential for antitumor 
activity that exceeds either agent’s monotherapy activity in preclinical models. Based on 
the current safety profiles (See Section 12.1 for details) and docetaxel labeling 
[TAXOTERE PI, 2020; TAXOTERE SmPC, 2020], potential overlapping toxicities with 
combination therapies are anticipated to be manageable. However, it is unknown whether 
the combination regimens will have clinical activity in NSCLC that exceeds the SoC 
treatment. Considering the overall poor outlook for patients who have failed prior 
therapies and recognizing the risk minimization strategies proposed, any potential risks 
are justified by the anticipated benefits to participants with advanced NSCLC.  
4. 
OBJECTIVES AND ENDPOINTS 
4.1. 
Objectives and Endpoints: Part 1  
Objectives 
Endpoints 
Primary 
To determine the safety and tolerability of novel 
regimen(s) 
AEs, SAEs, DLTs, changes in safety/laboratory 
assessment parameters, dose modifications 
Secondary 
To provide a preliminary evaluation of the efficacy of 
experimental regimen(s) 
Objective Response Rate (ORR) 
Disease Control Rate (DCR) 
Characterize the pharmacokinetic properties 
of experimental regimen(s) 
PK parameters that include Cmax and Cmin for 
experimental regimen(s) (and investigational agent/s 
included in other arms), as data permit. 
Exploratory 
4.2. 
Objectives and Endpoints: Part 2 
Objectives 
Endpoints 
Primary 
Determine whether experimental regimen(s) 
provide evidence for improved survival over 
SoC therapy 
Overall survival as measured by time from randomization to death 
Secondary 
Evaluate milestone survival in participants 
treated with experimental regimen(s) versus 
SoC therapy for NSCLC 
Milestone survival rate at 12 and 18 months  
Evaluate other measures of antitumor 
activity of the experimental regimen(s) 
compared with SoC therapy for NSCLC 
(RECIST 1.1 and iRECIST) 
CR, PR, SD, PD, PFS, ORR, DOR, DCR 
iCR, iPR, iUPD, iCPD, iSD 
iPFS; iORR; iDOR 
CCI


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Objectives 
Endpoints 
Evaluate the safety and tolerability of the 
experimental regimen(s) compared with 
SoC therapy for NSCLC 
 
Frequency and severity of AEs, AESI; SAEs and AE/SAEs leading to 
dose modifications/delays/withdrawals; changes in laboratory, vital 
signs, and safety assessment parameters, including immunogenicity 
(ADA) 
Characterize the pharmacokinetic properties 
of SoC or experimental regimen(s) 
PK parameters that may include Cmax and Cmin for experimental 
regimen(s) and for SoC alone, as data permit. 
Determine immunogenicity of experimental 
regimen(s) 
ADA incidence for experimental regimen(s) (where appropriate) 
Exploratory 
Note: The prefix “i”, used for response related abbreviations in the above table indicates immune responses assigned 
using iRECIST. 
AE = adverse event/s; AESI = adverse event/s of special interest; Cmax = maximum concentration; Cmin = minimum 
concentration; CPD = confirmed progression; CR = complete response; DLT = Dose Limiting Toxicity’ DOR = duration 
of response; 
 
; 
 
 
 ORR = objective response rate; OS = overall survival; PFS = progression-
free survival; 
 
 
; RECIST = Response Evaluation Criteria In 
Solid Tumors; SAE = serious adverse event; SD = stable disease; SoC = standard of care; TMB = Tumor Mutational 
Burden; UPD = unconfirmed progression. 
CCI
CCI
CCI
CCI


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5. 
STUDY DESIGN 
5.1. 
Overall Design 
This is an, open-label, platform trial in two parts utilizing a master protocol to study 
novel drug combinations compared with the current SoC in the treatment of patients with 
advanced NSCLC who have progressed on prior anti-PD(L)1 and platinum-based 
combination chemotherapies. Part 1 is a non-randomized, safety and PK/PD evaluation, 
Part 2 is a randomized, Phase II comparing the efficacy and safety of novel regimens with 
docetaxel as the SoC control arm (Arm 1). Novel combinations will be evaluated in 
separate substudies. As shown in Figure 1, the study will initially evaluate the efficacy of 
feladilimab in combination with SoC (docetaxel) (Arm 2) compared with SoC alone as 
the standard subsequent-line chemotherapy (substudy 1) in NSCLC. Additional arms will 
be added via protocol amendment based on emerging nonclinical and clinical data. No 
treatment crossover is allowed in this study. 
Each novel combination will first be evaluated for safety. This evaluation may occur 
prior to adoption into the 205801 platform study (dose finding in a separate study) or as a 
distinct arm within this platform study (Part 1) prior to Part 2. Following the initial safety 
evaluation, additional participants for each regimen and/or dose may be enrolled to 
further evaluate safety and PK/PD (refer to Section 12.1 for details for each experimental 
regimen).  Once an experimental regimen qualifies for transition evaluation, additional 
participants will be enrolled to Part 2. Within Part 2, participants will be randomized to 
receive either SoC or the experimental treatment. Part 2 treatment arms may be dropped 
based on interim OS results (Section 10.3.3). Part 1 is open label single arm while Part 2 
is randomized. Combinations that proceed to Part 2 will be tested in a new group of 
participants, separate from Part 1 participants, that will be randomized between the 
combination and the Standard of Care. The study participants enrolled in Part 1 are not 
pooled with the study participants in Part 2. The two study populations are separate and 
distinct. Data from Part 1 and 2 will not be combined. 
The data generated from each experimental regimen and associated control arm data are 
considered a substudy within the overall platform study, as depicted in Figure 1.  


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Figure 1 
Study Design 
 
NSCLC: non-small cell lung cancer; PD(L)1: Programmed Cell Death Protein 1 and Programmed Cell Death 
Ligand 1.  
Note: Randomization of participants to experimental regimens may not occur in parallel. It should be noted that 
the terms ‘regimen’ and ‘arm’ may be used interchangeably throughout the document. Between 10-20% of newly 
enrolled participants in substudies (depending upon the number of experimental arms in the trial) will be 
randomized to SoC once the initial 35 participants have been enrolled on control arm. 
 
Interim safety and efficacy data for Part 2 will be reviewed by an Independent Data 
Monitoring Committee (IDMC), independent of the study team. Additional details will be 
provided in an IDMC Charter. A Steering Committee of lead investigators on study will 
also be established to provide guidance for key decisions such as introduction of new 
arms and graduation of existing arms. 
At study start, participants will be randomized 1:2 to Arm 1 (SoC) and Arm 2, i.e., 33% 
and 67%, respectively. As new substudies are initiated, the randomization ratio will be as 
described below in Table 1. Between 10-20% of newly enrolled participants in 
subsequent substudies (depending upon the number of experimental arms in the trial) will 
be randomized to SoC once the initial 35 participants have been enrolled on control.  
The 1:4 randomization for a 2-arm trial is for subsequent substudies where a new 
experimental arm enters the trial and the SoC arm has already enrolled more than 
35 participants, and all other experimental arms are no longer enrolling (e.g. completed 
accrual, or stopped due to toxicity findings, or other reason). Similarly, the 1:4:4 
randomization for a 3-arm trial is for subsequent substudies where 2 new arms enter after 
the SoC arm has already enrolled more than 35 participants, and all other experimental 
arms are no longer enrolling (e.g. completed accrual, or stopped due to toxicity findings, 
or other reason). 


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Table 1 
Randomization Ratio and Proportion of Participants Randomized to 
the SoC Arm When There Are Concurrent Arms 
 
Randomization Ratio 
 
 ≤35th participants 
>35th participants 
Two arms  
(SoC and one treatment) 
1:2 SoC:Each Trt 
1:4 SoC:Each Trt 
Three arms  
(SoC + two treatments) 
1:2 SoC:Each Trt 
1:4 SoC:Each Trt 
Four arms  
(SoC + three treatments) 
1:1 SoC:Each Trt 
1:3 SoC:Each Trt 
Five arms or more 
(SoC + four or more treatments) 
1:1 SoC:Each Trt 
1:2 SoC:Each Trt 
 
The study will employ a Bayesian decision-making framework based on the predictive 
probability of observing a significant improvement in OS in a future Phase 3 trial (see 
Section 10.5.1 for details). 
Interim analysis of OS in Part 2 will be performed for each substudy after approximately 
45 events (experimental arm and SoC combined) and a minimum of 18 events from 
experimental arm have been observed. Note, events from the SoC arm will be counted 
from the initial study start (i.e. SoC events from substudy 1 will be counted with any 
further events observed in subsequent substudies). Participants will continue to be 
enrolled during interim analyses. The final analysis for each substudy will be performed 
once a minimum number of events have been observed. At the final analysis, the 
experimental regimen within a substudy may be recommended for proceeding to a Phase 
3 trial if it meets the predefined criteria for clinical activity. Details of the interim 
analysis and predefined criteria are provided in Section 10.3.3 and Section 10.3.4. 
The requirements for the experimental regimens to advance from earlier Phase I studies 
to the current Phase II study (205801) include:  
1. Determination of the recommended Phase II dose (RP2D) regimen  
2. Adequate safety data of the combination at the RP2D  
3. For the novel/novel combinations, evidence of potential antitumor activity in the 
range of the comparator (currently docetaxel) in an unselected solid tumor 
population.  
Additional experimental regimens or populations with the appropriate SoC arm may be 
introduced to the current design via protocol amendments; these experimental arm(s) may 
include novel agents other than the aforementioned agents (Figure 1). A biomarker-
driven approach may be implemented for any of the experimental arms as an enrichment 
strategy whereby participants will be stratified based on a biomarker test result prior to 
treatment allocation. The rationale for the biomarker-driven approach in selecting 
participants most likely to derive clinical benefit from that particular regimen will be 
fully delineated in the amendment(s). 


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5.2. 
Duration of Treatment 
The study consists of 3 periods: screening, treatment, and follow-up. The total duration of 
study participation begins with the signing of the informed consent form (ICF). 
Participants will provide informed consent within 45 days prior to the first dose. After a 
screening period of up to 28 days, eligible participants will be assigned a treatment arm if 
participating in Part 1 and receive study treatment (Day 1) or randomly assigned to a 
treatment arm (SoC or experimental) if participating in Part 2 and receive study treatment 
(Day 1) as specified in the SoA for each arm (Section 12.1).  
Combination study treatment will continue to be administered at the indicated schedule 
for a maximum duration of approximately 2 years or up to 35 treatment visits (unless 
noted otherwise in sections specific to each arm), whichever comes first, or until disease 
progression as determined by iRECIST, death, unacceptable toxicity, or other protocol-
defined criteria are met. Single agent SoC treatment (i.e., docetaxel) may continue until 
disease progression, death, unacceptable toxicity, withdrawal of consent, or per 
institutional standard for docetaxel. After study treatment is permanently discontinued, 
participants will be followed for adverse events (AEs).  
iRECIST is based on RECIST 1.1 but adapted to account for the unique tumor response 
seen with immunotherapeutic drugs [Seymour, 2017]. Participants who attain a 
confirmed complete response (CR) per iRECIST, have received at least 2 additional 
doses of study treatment beyond the date the initial CR was declared, and have been 
treated for a minimum of 6 months, may discontinue study treatment; and these 
participants will continue with the scheduled disease assessments (Section 9.3.1). 
Participants may be permitted to resume study treatment upon disease progression 
following consultation between the treating investigator and the Sponsor/Medical 
Monitor, and upon written consent by the participant. See Section 8.1 for specific 
conditions under which a participant may continue study treatment beyond disease 
progression. 
Participants who permanently discontinue study treatment will enter the survival 
follow-up period of the study and undergo the assessments as indicated in Section 9. 
5.3. 
Number of Participants 
As the study uses a master protocol design, the sample size for the study overall is not 
fixed. Participants enrolled to Part 1 will be separate from those enrolled to Part 2. 
5.3.1. 
Sample Size: Part 1  
For Part 1, sample size will be defined for each regimen under the corresponding 
appendix in Section 12.1; a minimum of 3 participants will be evaluated for safety during 
the 21 day DLT period before further participants will be enrolled. 
 


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5.3.2. 
Sample Size: Part 2 
The initial number of participants in Part 2 is estimated to be at least 105 in substudy 1 
(SoC arm: 35; experimental arm: 70). Additional experimental regimens may be added 
via protocol amendments and will be considered as another substudy. Each additional 
experimental arm will enroll a maximum of 70 participants. The minimum sample size 
for the SoC arm is 35 with additional participants randomized to SoC concurrently with 
additional experimental arms/substudies. Further randomization to SoC will be 
minimized once 35 patients are enrolled in the first substudy. Refer to Table 1 in Section 
5.1 and Section 10.3 for additional details on sample size determinations.  
Participants who discontinue in Part 2 will not be replaced in this study. See Section 10.4 
for definitions of the populations for analyses. 
5.4. 
Participant Completion and End of Study Definitions 
5.4.1. 
Participant Completion Definitions 
A participant will be considered to have completed the study if the participant dies during 
the study treatment period or follow-up period, whichever is sooner, or is still in follow-
up at the time of the final analysis. The cause of death will be documented in the 
CRF/eCRF. A participant will be considered to have withdrawn from the study if the 
participant has not died and is lost to follow-up, has withdrawn consent, at the 
investigator’s discretion is no longer being followed or if the study is closed/terminated. 
5.4.2. 
Study Completion Definition 
Substudy completion: A substudy is considered to have completed once the agreed 
number of events has been reached, survival follow up for remaining patients may not be 
needed.  
 
An arm may close during Part 1 for safety or tolerability reasons or if an insufficient 
number of responders in Part 1 of that arm have been observed. 
 
The end of study is defined as the completion of the last participant’s required study visit, 
telephone contact, or death, as applicable, in the last substudy.  
5.5. 
Scientific Rationale for Study Design 
The study will employ a platform design utilizing a master protocol to compare 
experimental therapies with a common SoC treatment. Novel regimens may enter Part 2 
via protocol amendment(s) once adequate safety and preliminary clinical activity data are 
obtained. If sufficient safety and preliminary clinical activity data are not available for a 
proposed regimen from other studies, these data may be obtained during a safety and 
PK/PD evaluation option in this study in Part 1. Once a regimen has passed criteria for 
safety and preliminary clinical activity, the treatment arm/regimen will be analyzed 
relative to the SoC treatment (Part 2) and is considered a substudy within the overall 
master protocol. In addition, different disease settings may be investigated via protocol 
amendment(s) and would introduce the SoC treatment for that setting. This design 


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provides efficiencies in the evaluation of experimental therapies by using a common 
control arm and discontinuing therapies that are deemed ineffective at interim time points 
while continuing randomization into substudies that may be more efficacious and be 
subsequently evaluated in confirmatory studies. The SoC arm will remain open to 
random assignment and the anticancer activity of experimental regimens in substudies 
that enter the study later will be compared with the overall population treated by the SoC 
therapy. Thus, the SoC population will always include contemporaneous as well as 
historical data.  
5.5.1. 
Steering Committee and Data Monitoring Committee (Part 2) 
A Steering Committee of lead investigators on study and representatives of the Sponsor 
study team will be established to provide guidance for key decisions such as introduction 
of new arms and graduation of existing arms. The remit, membership, and roles and 
responsibilities of the Steering Committee will be described in a charter. 
An IDMC, independent of the study team, will be established to monitor efficacy and 
safety during the course of the trial. The remit, membership, and roles and responsibilities 
of the Data Monitoring Committee will be described in a charter. 
Key decisions of the Steering Committee as well as the IDMC will be documented and 
reported to regulatory agencies if requested, all participating principal investigators (PIs) 
and if required, Institutional Review Boards (IRBs)/Independent Ethics Committees 
(IECs) as appropriate with impactful decisions communicated as priority.  
5.6. 
Dose Justification 
Dose justification for all study drugs are located in the arm-specific appendices (Section 
12.1). 


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6. 
STUDY POPULATION 
Participants are eligible to be included in the study only if all of the criteria in Section 6.1 
and Section 6.2 apply. In addition, participants must fulfill additional inclusion/exclusion 
criteria for at least one arm. Criteria for each individual arm can be found in the 
respective appendices for each arm, reported in Section 12.1. 
Prospective approval of protocol deviations to recruitment and enrollment criteria 
(waivers or exemptions) is not permitted.  
6.1. 
Inclusion Criteria 
1. Capable of giving signed informed consent/assent as described in Section 12.4 
which includes compliance with the requirements and restrictions listed in the ICF 
and in this protocol 
2. Male or female, aged 18 years or older at the time consent is obtained 
   Note: Participants in Korea must be age 19 years or older at the time consent is 
obtained.    
3. Histologically or cytologically confirmed diagnosis of NSCLC (squamous or non-
squamous) and: 
a. Documented disease progression based on radiographic imaging, during or 
after a maximum of 2 lines of systemic treatment for locally/regionally 
advanced recurrent, Stage IIIb/Stage IIIc/Stage IV or metastatic disease  
Two components of treatment must have been received in the same line or as 
separate lines of therapy:  
i. no more than or less than 1 line of platinum-containing chemotherapy 
regimen, and  
ii. no more than or less than 1 line of PD(L)1 mAb containing regimen. 
Notes: 
o PD(L)1 mAb received during a previous clinical trial may meet 
this requirement upon consultation with study medical monitor. 
o Participants who received a regimen similar to the PACIFIC 
regimen [chemoradiotherapy followed by PD(L)1] as part of 
SoC AND have relapsed within one year from the first dose of 
chemoradiotherapy would fulfill the protocol requirement for 
platinum-based chemotherapy treatment and PD-1/L1 
treatment. This would be considered a single line of treatment 
for the purpose of PD(L)1 line of therapy stratification. 
o PD(L)1 mAb can be administered with the platinum-based 
chemotherapy regimen and this would count as a single line of 
therapy. 
o PD(L)1 mAb may be counted as a prior treatment if the agent 
is approved in at least 1 country for the treatment of cancer.  


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o Participants who have completed 2 years of pembrolizumab or 
another PD(L)1 mAb, discontinue from that therapy, 
experience disease progression, and are then retreated with 
PD(L)1, will be considered as having had one line of PD(L)1 
therapy. 
o Adjuvant or neo-adjuvant systemic anticancer therapy will not 
count toward the 2 lines of therapy unless disease recurs during 
the first year following the start of adjuvant chemotherapy. 
b. Participants with known BRAF molecular alterations must have had disease 
progression after receiving the locally available SoC treatment for the 
molecular alteration. 
c. Participants who received prior anti-PD(L)1 therapy must fulfill the following 
requirements: 
o Have achieved a CR, PR or SD and subsequently had disease progression 
(per RECIST 1.1 criteria) either on or after completing PD(L)1 therapy 
o Have not progressed or recurred within the first 12 weeks of PD(L)1 
therapy, either clinically or per RECIST 1.1 criteria 
 
4. Measurable disease, presenting with at least 1 measurable lesion per RECIST 1.1 
(see Appendix 12 for definition of a measurable lesion) 
5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 
0 or 1 
6. A tumor tissue sample obtained at any time from the initial diagnosis of NSCLC to 
time of study entry is mandatory. Although a fresh tumor tissue sample obtained 
during screening is preferred, archival tumor specimen is acceptable. See Study 
Reference Manual (SRM) and Section 9.9.2 for further details on tumor tissue 
requirements. 
7. Adequate organ function as defined in Table 2.  


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Table 2 
Definitions of Adequate Organ Function 
System 
Laboratory Values 
Hematologica 
ANC (Absolute Neutrophil Count) 
1.5 x 109/L (≥1500/µL) 
Hemoglobin 
9 g/dL or ≥5.6 mmol/L 
Platelets 
100 x 109/L (≥100 000/µL) 
Hepatic 
Albumin 
≥2.5 g/dL 
Total bilirubin 
 
 
Patients with Gilbert’s Syndrome (only if direct bilirubin 35%) 
1.5 x ULN (isolated bilirubin >1.5 x ULN is 
acceptable if bilirubin is fractionated and 
direct bilirubin <35%) 
3.0 x ULN 
ALT (SGPT) 
2.5 x ULN, OR  
≤5 X ULN for participants with documented 
liver metastases 
Renal 
Calculated CrClb 
≥30 mL/min 
Abbreviations: ALT = alanine aminotransferase; CrCL = creatinine clearance; SGPT = serum glutamate-pyruvate 
transaminase; ULN = upper limit of normal. 
a.   Participants may be transfused or receive growth factor treatment to meet minimum hematologic values up to 7 
days prior to determining eligibility. Absolute Lymphocyte Count will be included in the baseline assessment, but 
no range limit requirement for eligibility. 
b.   Calculated CrCL is required to be calculated using the Chronic Kidney Disease Epidemiology Collaboration 
(CKD-EPI) or Cockcroft-Gault formula. Either formula is acceptable and must be consistently utilized for each 
participant throughout the study (Appendix 9). 
 
8. A male participant must agree to use a highly effective contraception as detailed in 
Appendix 6 of this protocol during the treatment period and for at least 120 days 
after the last dose of study treatment and refrain from donating sperm during this 
period. Unless otherwise specified under each arm in Section 12.1 
Note: If the participant is randomized to the SoC regimen only, duration of 
contraception should be as per local label.  
9. A female participant is eligible to participate if she is not pregnant (see 
Appendix 6), not breastfeeding, and at least 1 of the following conditions apply: 
i. 
Not a woman of childbearing potential (WOCBP) as defined in 
Appendix 6  
 
OR 
 
ii. 
A WOCBP who agrees to follow the contraceptive guidance in 
Appendix 6 during the treatment period and for at least 120 days after the 
last dose of study treatment.  
Note: If the participant is randomized to the SoC regimen only, duration 
of contraception should be as per local label. 
10. Life expectancy of at least 12 weeks 


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6.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
1. Received prior treatment with the following therapies (calculation is based on 
date of last therapy to date of first dose of study treatment): 
a. Docetaxel at any time 
b. Any of the investigational agents being tested in the current study, refer 
to Section 12.1 for additional information 
c. Systemic approved or investigational anticancer therapy within 30 days 
or 5 half-lives of the drug, whichever is shorter. At least 14 days must 
have elapsed between the last dose of prior anticancer agent and the 
first dose of study drug is administered.  
d. Prior radiation therapy: permissible if at least one non-irradiated 
measurable lesion is available for assessment per RECIST version 1.1 
or if a solitary measurable lesion was irradiated, objective progression 
is documented. A wash out of at least 2 weeks before start of study 
drug for radiation of any intended use is required. 
2. Received >2 prior lines of therapy for NSCLC, including participants with BRAF 
molecular alterations. (See inclusion criterion #3 for eligible lines of therapy 
guidance) 
Note: Patients with known molecular alterations with therapeutic options available 
(e.g., EGFR, ALK, ROS1) are excluded from participation in this study, unless no 
other therapeutic options are available locally.  
3. Invasive malignancy or history of invasive malignancy other than disease under 
study within the last 2 years, except as noted below: 
• Any other invasive malignancy for which the participant was definitively 
treated, has been disease-free for at least 2 years and in the opinion of the 
principal investigator and GSK Medical Monitor will not affect the evaluation 
of the effects of the study treatment on the currently targeted malignancy, may 
be included in this clinical trial.  
• Curatively treated non-melanoma skin cancer or successfully treated in situ 
carcinoma of the skin.  
4. Carcinomatous meningitis (regardless of clinical status) and uncontrolled or 
symptomatic central nervous system (CNS) metastases.  
 
Note: Participants with previously treated brain metastases may participate 
provided they are asymptomatic (any neurologic symptoms have returned to 
baseline [participants may be receiving stable doses of anticonvulsants]), 
radiographically stable (without evidence of progression by imaging for at least 4 


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weeks prior to the first dose of study treatment), have no evidence of new or 
enlarging brain metastases, and are clinically stable off steroids for at least 2 
weeks prior to study treatment.  
5. Major surgery 28 days of first dose of study treatment. 
6. Autoimmune disease (current or history) or syndrome that required systemic 
treatment within the past 2 years (Refer to Appendix 14). Replacement therapies 
which include physiological doses of corticosteroids for treatment of 
endocrinopathies (for example, adrenal insufficiency) are not considered systemic 
treatments.  
Note: Participants with controlled Type 1 diabetes mellitus (T1DM) are eligible. 
7. Receiving systemic steroids (>10 mg oral prednisone or equivalent) or other 
immunosuppressive agents within 7 days prior to first dose of study treatment. 
Note: Steroids as premedication for hypersensitivity reactions (e.g., computed 
tomography [CT] scan premedication) are permitted. Use of inhaled  
corticosteroids, local steroid injection, or steroid eye drops is allowed.  
8. Prior allogeneic/autologous bone marrow or solid organ transplantation. 
9. Receipt of any live vaccine within 30 days prior to first dose of study treatment.  
Refer to the SRM for clarity on COVID-19 vaccines. 
10. Toxicity from previous anticancer treatment that includes: 
a. ≥ Grade 3 toxicity considered related to prior immunotherapy and that led to 
treatment discontinuation. 
b. Toxicity related to prior treatment that has not resolved to ≤Grade 1 (except 
alopecia, hearing loss, endocrinopathy managed with replacement therapy, and 
peripheral neuropathy which must be ≤Grade 2). 
11. History (current and past) of idiopathic pulmonary fibrosis, pneumonitis (for past 
pneumonitis exclusion only if steroids were required for treatment), interstitial 
lung disease, or organizing pneumonia.  
 
Note: post-radiation changes in the lung related to prior radiotherapy and/or 
asymptomatic radiation-induced pneumonitis not requiring treatment may be 
permitted if agreed upon by the investigator and Medical Monitor. 
12. Recent history (within the past 6 months) of uncontrolled symptomatic ascites, 
pleural or pericardial effusions 
13. Recent history (within the past 6 months) of gastrointestinal obstruction that 
required surgery, acute diverticulitis, inflammatory bowel disease, or intra-
abdominal abscess 


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14. History or evidence of cardiac abnormalities within the 6 months prior to 
enrollment which include: 
a. Serious, uncontrolled cardiac arrhythmia or clinically significant 
electrocardiogram abnormalities including second degree (Type II) or third 
degree atrioventricular block. 
b. Cardiomyopathy, myocardial infarction, acute coronary syndromes (including 
unstable angina pectoris), coronary angioplasty, stenting or bypass grafting 
c. Symptomatic pericarditis. 
15. Current unstable liver or biliary disease per investigator assessment defined by the 
presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal 
or gastric varices, persistent jaundice, or cirrhosis.  
Note: Stable chronic liver disease (including Gilbert's syndrome or asymptomatic 
gallstones) is acceptable if participant otherwise meets entry criteria. 
16. Active infection requiring systemic therapy ≤7 days prior to first dose of study 
treatment.  
17. Known human immunodeficiency virus infection 
18. History of severe hypersensitivity to monoclonal antibodies or hypersensitivity to 
any of the study treatment(s) or their excipients. 
19. Requires ongoing therapy with a medication that is a strong inhibitor or inducer of 
the cytochrome 3A4 (CYP3A4) enzyme (Flockhart, 2018). This criterion is 
applicable to only those participants in treatment arms containing docetaxel. 
20. Any serious and/or unstable pre-existing medical (aside from malignancy), 
psychiatric disorder, or other condition that could interfere with participant’s 
safety, obtaining informed consent, or compliance to the study procedures in the 
opinion of the investigator 
21. Pregnant or lactating female participants 
22. Is currently participating in or has participated in a study of an investigational 
device within 4 weeks prior to the first dose of study treatment.  
23. Presence of hepatitis B surface antigen (HBsAg) at screening or within 3 months 
prior to first dose of study intervention 
24. Positive hepatitis C antibody test result at screening or within 3 months prior to 
first dose of study intervention. 
NOTE: Participants with positive Hepatitis C antibody due to prior resolved disease 
can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained. 


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25. Positive hepatitis C RNA test result at screening or within 3 months prior to first 
dose of study treatment.  
NOTE: Test is optional and participants with negative Hepatitis C antibody test are 
not required to also undergo Hepatitis C RNA testing.  
 
26. Receipt of transfusion of blood products (including platelets or red blood cells) or 
administration of colony-stimulating factors (including granulocyte colony 
stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor, and 
recombinant erythropoietin) within 14 days before the first dose of study intervention. 
 
6.3. 
Lifestyle and Dietary Restrictions 
No lifestyle restrictions are planned for this study however male participants with 
partners of childbearing potential and women of childbearing potential must utilize 
appropriate contraception as described in Section 12.6.  
Participants should maintain a normal diet unless modifications are required to manage 
an AE such as diarrhea, nausea, or vomiting. However, foods that are CYP3A inhibitors 
must not be consumed during the study for those participants in Part 2 on Docetaxel arm. 
Grapefruit, star fruit, and pomegranate are known to be CYP3A inhibitors, and should not 
be consumed for 2 weeks before the first dose of docetaxel and for at least 2 weeks after 
the last dose of docetaxel. Note that consumption of CYP3A4 inhibitors such as these 
may significantly increase the levels of docetaxel. St. John’s Wort is a CYP3A inducer, 
and the consumption of St. John’s Wort or products containing St. John’s Wort may 
reduce the levels of docetaxel.  
6.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study 
but are not subsequently randomized/entered in the study. 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 
participant and the subsequent screening result, if within range, may be used to confirm 
eligibility. Individuals who do not meet the criteria for participation in this study (screen 
failure) may be rescreened. Rescreened participants must be assigned a new unique 
participant number that is different from the initial number. 
A minimal set of screen failure information is required to ensure transparent reporting of 
screen failure participants to meet the Consolidated Standards of Reporting Trials 
(CONSORT) publishing requirements and to respond to queries from regulatory 
authorities. Minimal information includes demography, screen failure details, eligibility 
criteria, and any SAEs. 


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6.5. 
Screening under Molecular Disease Characterization 
Initiative Study 
Participants may be initially screened under GSK protocol 213299 (a molecular disease 
characterization initiative study) where it is IRB/IEC approved at a site and then referred 
to this study 205801. Screening assessments performed under protocol 213299 may be 
accepted for the enrollment into this GSK protocol 205801 to avoid any repeat screening 
tests. 
Baseline Biopsy: 
If a biopsy was acquired under GSK protocol 213299, tissue blocks/slides from this 
biopsy may be used for additional screening or baseline analyses required by this 
protocol (205801). Another biopsy may be needed for treatment specific screening at 
baseline in cases where there is not enough remaining material from biopsy acquired 
under GSK protocol 213299. 
Screening/Baseline Imaging and Other Assessments: 
If radiographic imaging was performed under GSK protocol 213299, those images may 
be used for screening/baseline disease assessment. Images must meet the acceptable 
scanning modalities and anatomical coverage required for this protocol (205801). 
Additional scans may be needed to meet inclusion/exclusion criteria, safety requirements, 
or other anatomical areas as required by this protocol (205801). Additional scans are 
required if imaging falls outside the screening/baseline acceptable visit window. 
Please refer to SRM for more information.  
7. 
TREATMENTS 
Study treatment is defined as any investigational treatment(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant per the 
study protocol. 
7.1. 
Treatments Administered 
The term study treatment(s) is used throughout the protocol as a general descriptor for 
any or all treatment arms/regimens or the individual agents. 
All investigational agents utilized in this study will be provided to sites by the Sponsor. 
Docetaxel will be sourced locally from commercial stock, except in countries where local 
regulations mandate that the Sponsor supply all study treatment(s) required for the trial.  
As additional substudies are initiated, treatment details for experimental regimens from 
those substudies will be provided in Section 12.1. 


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7.2. 
Dose Modification 
Dose modifications, including interruptions and reductions, may occur for the 
management of AEs according to the current product label for SoC (e.g., docetaxel) and 
guidelines provided in the protocol for investigational agents. 
Note: If a participant, randomized to an experimental treatment arm, experiences a 
toxicity attributable to one of the drugs in the combination, the investigator may 
discontinue the responsible drug but continue treatment with the other drug. In all such 
scenarios, the SoA applicable to the active treatment(s) must be followed.  
Additional dose modification guidelines for specific experimental regimens will be 
provided in Section 12.1 as needed when new substudies are initiated.  
7.2.1. 
Dose and Safety Management Guidelines 
7.2.1.1. 
General Guidelines for Immune-Related Adverse Events (irAEs) 
AEs associated with immunotherapy treatment may be immune-mediated. These 
immune-related AEs (irAEs) may occur shortly after the first dose or several months after 
the last dose of treatment, or during the treatment course, and may affect more than one 
body system simultaneously. Therefore, early recognition of and initiation of treatment 
for these events is critical to reduce potential complications.  
For suspected irAEs, ensure adequate evaluation to confirm the etiology or exclude other 
causes. Additional procedures or tests such as, but not limited to, bronchoscopy, 
endoscopy, or skin biopsy may be included as part of the evaluation. Based on the 
severity of irAEs, withhold or permanently discontinue treatment and administer 
corticosteroids and/or immuno-modulators. Dose modification and toxicity management 
guidelines for irAEs associated with immunotherapies are provided for each arm in the 
respective subsections under Section 12.1.  
Note: This guidance does not apply to participants randomized to Arm 1 SoC 
chemotherapy in Part 2. 
Before administration of study treatment, investigators are to review a participant’s AEs, 
concomitant medications, and clinical evaluation results, e.g., vital signs, laboratory 
results, ECOG PS, physical examination findings, responses, etc. as outlined in the 
Schedule of Activities (Section 12.1) to monitor for new or worsening irAEs and ensure 
continued dosing is appropriate.  
Adverse Events of Special Interest (AESI) 
AESI are considered to be Infusion Related Reactions (IRRs) and those of potential 
immunologic etiology, including irAEs. Such events recently reported after treatment 
with other immune modulatory therapy include, but are not limited to, the following: 
pneumonitis, nephritis, hepatitis, colitis, immune related endocrinopathies (such as 
thyroiditis or hypophysitis) or immune related cutaneous toxicities, to include rashes 
confirmed via biopsy to be immune-mediated.  
AESIs will be reported within 24 hours if the event meets the criteria for a serious event.  


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Dose modification and toxicity management guidelines for irAEs are provided for each 
arm in the respective subsections under Section 12.1. 
7.2.1.2. 
Dose Modification and Toxicity Management of Infusion-Reactions 
Related to Immunotherapy Treatment  
Infusion reactions are a well-documented AE associated with the administration of 
monoclonal antibodies (mAbs). Infusion reactions typically develop within 30 minutes to 
2 hours after initiation of drug infusion, although symptoms may be delayed for up to 48 
hours. The incidence of infusion reactions varies by mAb agent, and there are multiple 
mechanisms known to lead to infusion-related reactions including both IgE-dependent 
anaphylactic and non-IgE dependent anaphylactoid hypersensitivities. Cytokine release 
syndrome (CRS), and when severe, cytokine “storm”, has been identified as a sequela of 
the immune system activation associated with infusion reactions. 
Infusion reactions may affect any organ system in the body. Most are mild in severity, 
although severe and even fatal reactions occur. As a group, infusion reactions (including 
both cytokine-mediated and allergic) usually occur during or within a few hours of drug 
infusion. Occasionally, a reaction may occur 1 to 2 days after administration. The NCI-
CTCAE (version 5.0) for grading adverse reactions during chemotherapy administration 
has a scale for grading the severity of infusion reactions and separate grading scales for 
allergic reactions and anaphylaxis. While use of these separate grading scales may be 
useful for classifying the nature of an infusion reaction for research purposes, they are 
less useful for clinical care, since it may not be obvious if the participant is having an 
allergic infusion reaction or a non-allergic infusion reaction.  
Clinically, an acute-onset infusion reaction may present with flushing, itching, urticaria, 
and/or angioedema, repetitive cough, sudden nasal congestion, shortness of breath, chest 
tightness, wheeze, sensation of throat closure or choking, and/or change in voice quality, 
faintness, tachycardia (or less often bradycardia), hypotension, hypertension and/or loss 
of consciousness, nausea, vomiting, abdominal cramping, and/or diarrhea, sense of 
impending doom, tunnel vision, dizziness, and/or seizure, severe back, chest, and pelvic 
pain. Dose modification and treatment guidance for immunotherapy infusion reactions 
are provided for each arm in the respective subsections under Section 12.1. 
To better understand the underlying etiology of these events, serum tryptase, C-reactive 
protein (CRP), ferritin, and a cytokine panel should be drawn during the occurrence of an 
infusion reaction/CRS of any grade as outlined in Table 3. Only if not possible to collect 
at the occurrence of the event, samples should be drawn as soon as possible after the 
event and within 24 hours. The serum tryptase, CRP and ferritin panels must be 
performed at the investigator’s designated local laboratory. The serum cytokine panel 
will be performed at a GSK designated laboratory. These data will aid in the classifying 
(albeit retrospectively) the etiology of the infusion reaction AE. Infusion-related reaction 
management guidelines are provided for each study arm in Section 12.1.  


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Table 3 
Infusion-Related Reaction Laboratory Panel 
Biomarker 
Relationship to Adverse Event 
Serum tryptasea 
IgE-related infusion reaction (Allergic/anaphylaxis) 
[Schwartz, 2006] 
Serum CRPa 
Elevated in CRS [Lee, 2014] 
Serum ferritina 
Elevated in CRS [Lee, 2014] 
Serum cytokine panelb 
(IFN-γ*^, TNF-α*^, IL-2*, IL-4, IL-6*^, IL-8*, IL-10*, IL-12p70, 
and IL-13) 
* Reported to be elevated in CRS [Lee, 2014] 
^ Consistently reported as elevated in CRS [Lee, 
2014] 
CRP = C-reactive protein; CRS = Cytokine release syndrome; IFNγ = Interferon gamma; TNFα = Tumor necrosis factor 
alpha; IL = Interleukin.  
a. Performed by investigator designated local laboratory if available; otherwise performed by GSK designated 
laboratory 
b. Performed by GSK designated laboratory 
 
7.2.1.3. 
Management Guidance of Chemotherapy-related Toxicities 
Refer to Table 4 and Table 5 for guidance on specific chemotherapy-related AEs; refer to 
chemotherapy prescribing information or standard practice guidelines for the 
management of these AEs, other AEs or potential safety-related issues. 
Table 4 
Dose Reductions for Docetaxel-related Hematologic Events 
Chemotherapy Regimen 
Toxicity 
Actiona 
Docetaxel 
• 
ANC <1.5x109/L, platelets 
<75x109/L, or hemoglobin <9g/dL 
(after transfusion if needed) 
 
 
 
 
• 
Febrile neutropenia 
• 
Hold docetaxel until recovery: 
ANC 1.5x109/L, platelets 
100x109/L  
• 
Recovery within 7 days, 
resume 100% of previous 
dose; >7 days, resume 80% 
of previous dose 
• 
Hold docetaxel; upon 
recovery, if ANC <500/mm3 
for more than 7 days, resume 
at 55 mg/mm2 
a. 
Resume treatment with chemotherapy after resolution as indicated; treatment with other study treatment may 
continue unless otherwise instructed. 
Table 5 
Dose Reductions for Docetaxel-related Non-Hematologic Events 
Chemotherapy Regimen 
Toxicity 
Actiona 
Docetaxel 
• 
Grade 3/Grade 4 event (including 
severe or cumulative cutaneous 
reactions), except peripheral 
neuropathy 
 
 
• 
Grade 3/Grade 4 peripheral 
neuropathies 
 
• 
Hold docetaxel upon recovery 
to Grade 1/baseline, resume 
treatment at 55 mg/mm2 
 
• 
Consider permanent 
discontinuation; discuss with 
Medical Monitor  
a. 
Resume treatment with chemotherapy after resolution as indicated; treatment with other study treatment may 
continue unless otherwise instructed. 


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Refer to docetaxel prescribing information or standard practice guidelines for the 
management of these AEs, other AEs or potential safety-related issues [TAXOTERE PI, 
2020]. 
7.2.1.4. 
Dose Delay for Toxicity or Other Illness 
If there is a dose delay between 1 and 7 days, the procedures required at the original 
scheduled visit (including dosing) should be performed as soon as possible. Refer to the 
SRM for instructions regarding assessments to be collected and how to record data in the 
eCRF. 
If the delay is 8 days, the visit and dose(s) will be considered missed. The procedures at 
the next regularly scheduled visit should be performed (with dosing), and subsequent 
visits will follow Q3W.  
Participants with infusion delays greater than 3 weeks due to toxicity should discontinue 
study drug(s) unless the treating investigator and Sponsor/Medical Monitor agree there is 
strong evidence supporting continued treatment.  
 
7.3. 
Method of Treatment Assignment 
Once determined to be eligible for the study, all participants will be centrally randomized 
using an Interactive Web Response System (IWRS). Before the study is initiated, the 
directions for the IWRS and log in information will be provided to each site. Once 
determined to be eligible for the study, participants must be randomized via IWRS. Study 
drug shipment will be managed via IWRS. Sites must allow up to 7 business days for 
shipment of study drug. 
Study treatment will be dispensed at the study visits summarized in SoA for treatments 
found within the SoA for each arm (Section 12.1). 
7.4. 
Blinding 
This is an open-label study. Sites will record the treatment assignment on the applicable 
eCRF. 
7.5. 
Preparation/Handling/Storage/Accountability 
7.5.1. 
Preparation 
Refer to the SRM for instructions on the preparation of investigational study treatments. 
Refer to the package insert for docetaxel preparation instructions.  
1. The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study treatment received and any discrepancies 
are reported and resolved before use of the study treatment. 
1. Only participants enrolled in the study may receive study treatment and only 
authorized site staff may supply or administer study treatment. All study treatments 


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must be stored in a secure, environmentally controlled, and monitored (manual or 
automated) area in accordance with the labeled storage conditions with access 
limited to the investigator and authorized site staff. 
2. The investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study treatment accountability, reconciliation, and record 
maintenance (i.e., receipt, reconciliation, and final disposition records). 
3. Further guidance and information for the final disposition of unused study treatment 
are provided in the SRM.  
 
7.5.2. 
Handling 
• 
Under normal conditions of handling and administration, study treatment is not 
expected to pose significant safety risks to site staff. Take adequate precautions to 
avoid direct eye or skin contact and generation of aerosols or mists. In case of 
unintentional occupational exposure notify the monitor, Medical Monitor, and/or 
GSK study contact. 
• 
A Material Safety Data Sheet (MSDS) or equivalent document describing 
occupational hazards and recommended handling precautions either will be 
provided to the investigator, where this is required by local laws, or is available 
upon request from GSK. 
7.5.3. 
Storage 
All study treatment must be stored in a secure environmentally controlled and monitored 
(manual or automated) area in accordance with the labeled storage conditions with access 
limited to the investigator and authorized site staff. 
Refer to the SRM for storage condition specifications and temperature monitoring 
requirements. 
7.5.4. 
Accountability 
• Only participants enrolled in the study may receive study treatment and only 
authorized site staff may supply or administer study treatment. 
• The investigator, institution, or the head of the medical institution (where 
applicable) is responsible for study treatment accountability, reconciliation, and 
record maintenance (i.e., receipt, reconciliation and final disposal records). 
• Further guidance and information for final disposition of unused study treatment 
are provided in the SRM.  
7.6. 
Treatment Compliance 
Study treatments will be intravenously administered to participants at the site. 
Administration will be documented in the source documents and reported in the eCRF. 


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7.7. 
Concomitant Therapy 
Participants will be instructed to inform the investigator prior to starting any new 
medications from the time of the first dose of study treatment until discontinuation of 
study treatment. Any permitted concomitant medication(s), including non-prescription 
medication(s) and herbal product(s), taken during the study will be recorded in the eCRF. 
The minimum requirement for reporting is drug name, dose, dates of administration, and 
the reason for medication. 
Questions regarding concomitant medications must be directed to the GSK Medical 
Monitor for clarification. 
If changes are made to the list of permitted/prohibited medications in the future, formal 
documentation will be provided by GSK and stored in the study file. Any such changes 
will be communicated to the investigative sites by letter.  
Refer to the drug interaction information in the product package inserts for precautions 
and prohibited concomitant medications related to docetaxel treatment [TAXOTERE PI, 
2020; TAXOTERE SmPC, 2020]. 
7.7.1. 
Permitted Medications and Non-Drug Therapies 
Participants receiving docetaxel should receive premedication/supplementation regimens 
according to the approved product label or standard practice. All participants should 
receive full supportive care during the treatment course of the study, including 
transfusion of blood and blood products, and treatment with antibiotics, antiemetics, 
antidiarrheals, and analgesics, as appropriate. Seasonal flu vaccine is permitted as an 
injection only, that is, intra-nasal flu vaccine is not permitted. Refer to the SRM for 
permitted COVID-19 vaccines. Elective palliative surgery or radiation may be permitted 
on a case-by-case basis in consultation with GSK Medical Monitor. 
The following medications are permitted as indicated: Please also refer to Section 12.1 
for medications specific to each experimental combination. 
a. 
Bisphosphonates and receptor activator of nuclear factor-kappaB ligand (RANKL) 
inhibitors (e.g., denosumab): Participants are required to have been on a stable dose 
for at least 4 weeks prior to receiving first dose of study treatment. Prophylactic use 
in participants without evidence or history of bone metastasis is not permitted, except 
for the treatment of osteoporosis. 
b. Growth factors: Prophylactic use of growth factors are not permitted during study 
treatment, unless clinically/therapeutically indicated for toxicity management.  
c. 
Steroids: Refer to Section 7.2.1 and the associated sub-sections for acceptable use 
while participant in on study treatment. Participants with pre-existing conditions 
requiring steroids are permitted to continue taking up to a maximum of 10 mg of 
prednisone or equivalent provided the participant has been on a stable dose for at 
least 28 days before first dose of study treatment; see exclusion criteria in Section 6.2 
for further requirements. Steroids used for chemotherapy premedication are 
permitted. 


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d. Prescribed medicinal cannabinoids are permitted during the study as palliative 
therapy. 
7.7.2. 
Prohibited Medications and Non-Drug Therapies 
The following medications are prohibited before the first dose of study treatment (see 
Section 6.2 for specific time requirements) and while on treatment in this study: Please 
also refer to Section 12.1 for medications specific to each experimental combination. 
• Anticancer therapies other than those referred to as Study Treatment that include, 
but are not limited to chemotherapy, immunotherapy, biologic therapy, hormonal 
therapy (other than physiologic replacement), surgery, and radiation therapy 
(other than palliative intervention as described in Section 7.7.1). 
• Any investigational drug(s) other than those referred to as Study Treatment. 
• Refer to the SRM for guidance on COVID-19 and other vaccines.  
• Strong CYP3A4 inhibitors and inducers for participants receiving docetaxel alone 
or in combination with another study drug (use as premedication is permitted). 
• Herbal preparations or related over the counter (OTC) preparations containing 
herbal ingredients that are known to affect CYP3A isoenzymes (e.g., St. John’s 
Wort) either during or within 2 weeks prior to the first dose of docetaxel. 
7.8. 
Treatment after the End of the Study 
The study participants will not receive any additional treatment from GSK after 
permanent discontinuation of study treatment. The investigator is responsible for 
ensuring that consideration is given to the post-study care of the participant’s medical 
condition. 
8. 
DISCONTINUATION CRITERIA 
8.1. 
Discontinuation of Study Treatment 
Participants will receive study treatment for the scheduled time period as indicated in 
Section 12.1 but must discontinue treatment if one of the following events occurs earlier:  
• 
Confirmed disease progression (iCPD as determined by iRECIST) 
• 
death 
• 
unacceptable toxicity, including meeting stopping criteria for liver chemistry 
abnormalities as defined in Appendix 10 
In addition, study treatment may be permanently discontinued for any of the following 
reasons: 
• 
deviation(s) from the protocol or non-compliance with study requirements 
• 
request of the participant or proxy (withdrawal of consent by participant or proxy) 
• 
discretion of the investigator  


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• 
participant is lost to follow-up 
• 
closure or termination of the study  
Continuation of Treatment Upon Disease Progression 
Participants who have disease progression (unequivocal disease progression) by RECIST 
1.1 may continue study treatment at the discretion of the Investigator with approval from 
the Medical Monitor, and upon separate written consent of the participant. Continuation 
on study treatment with disease progression is contingent upon the following conditions: 
• 
Participant has documented clinical benefit, 
• 
absence of clinical signs or symptoms indicating clinically significant disease 
progression, 
• 
no decline in ECOG performance status 
• 
absence of rapid disease progression or threat to vital organs or critical 
anatomical sites (e.g., CNS metastasis, respiratory failure due to tumor 
compression, or spinal cord compression) requiring urgent alternative medical 
intervention. 
• 
no significant, unacceptable, or irreversible toxicities related to study treatment. 
Termination of a Substudy/Experimental Arm 
If a substudy/experimental arm is terminated based on interim results and a participant is 
currently active in the substudy, receiving study treatment, and in the opinion of the 
investigator is deriving benefit from that treatment without evidence of disease 
progression, the participant may continue to receive study treatment upon agreement 
between the Sponsor and the investigator.  
Study Termination  
If the study is terminated by the Sponsor for reasons unrelated to safety or efficacy and a 
participant is currently active in the study, the Sponsor will notify the investigator of the 
study termination, further enrollment in the study will be terminated, and the Sponsor 
will communicate to investigative sites the discontinuation procedures and plans for 
discontinuation of patients from study treatment.  
Termination Due to Toxicity 
If the participant discontinues from treatment due to toxicity, the relevant AE will be 
recorded on the eCRF as the primary reason for permanent discontinuation.  
Termination from Study Treatment 
If a participant discontinues study treatment for reasons other than disease progression, 
does not have evidence of disease progression and chooses to continue in the study, the 
participant will continue study assessments according to the visit schedule described in 
the SoA for the specific arm in Section 12.1. The participant will be followed until 
disease progression by iRECIST or the start of a new systemic anti-cancer therapy, 
whichever comes first. 


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Procedures Following Discontinuation 
The primary reason for permanent study treatment discontinuation must be documented 
in the participant’s medical records and eCRF. 
Once a participant has permanently discontinued from study treatment, the participant 
will not be allowed to be retreated but will remain on the observational phase of the study 
for survival follow-up.  
All participants who discontinue from study treatment will have safety assessments at the 
time of discontinuation and during post-study treatment follow-up as specified in the SoA 
for the specific substudy in Section 12.1.   
All participants who permanently discontinue study treatment without disease 
progression will be followed for survival according to the protocol schedule until one or 
more of the following occur: 
• 
death 
• 
withdrawal of consent for the observational phase of survival follow-up 
In the observational phase of the study, all participants who permanently discontinue 
study treatment will be followed via telephone contact every 12 weeks from the date the 
last dose for survival and new anticancer therapy, including radiotherapy, until death or 
withdrawal from further contact. New anticancer therapy information should be reported 
in the eCRF for those participants who die before the first follow-up contact. 
Decisions regarding dose interruptions or modifications for reasons other than 
management of events as already described in this section and elsewhere in this protocol 
will be made by the investigator in consultation with the Medical Monitor based on the 
clinical evaluation of the participant. 
8.1.1. 
Liver Chemistry Stopping Criteria 
Liver chemistry stopping and increased monitoring criteria have been designed to 
assure participant safety and evaluate liver event etiology. 
Discontinuation of study treatment for abnormal liver tests is required when a participant 
meets one of the conditions outlined Figure 2 or Figure 3, based on baseline ALT: 


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Figure 2 
Liver Chemistry Stopping Criteria – Liver Stopping Event Algorithm 
for Participants with ALT up to 2.5 X ULN at Baseline 
 


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Figure 3 
Liver Chemistry Stopping Criteria – Liver Stopping Event Algorithm 
for Participants with documented liver metastases with ALT up to 5 
X ULN at Baseline 
 
The details on follow-up procedures are outlined in Appendix 10. 
Stopping Rules for Clinical Deterioration 
To adequately assess the antitumor effect of immunotherapeutic agents it is reasonable to 
allow participants experiencing apparent progression as defined by RECIST 1.1 
guidelines to continue to receive treatment until progression is confirmed at the next 
imaging assessment at least 4 weeks later as indicated by iRECIST guidelines. 
Nevertheless, these considerations should be balanced by clinical judgment as to whether 
the participant is clinically deteriorating and unlikely to receive any benefit from 
continued study treatment. 
In cases where deterioration was assessed to have occurred after a clinical event that, in 
the investigator’s opinion, is attributable to disease progression and is unlikely to reverse 
with continued study treatment or managed by supportive care (e.g., bisphosphonates 
and/or bone directed radiotherapy, thoracentesis, or paracentesis for accumulating 
effusions), study treatment should be discontinued. In these cases, the decision to 
continue treatment must be discussed with the Sponsor’s Medical Monitor and written 
consent by the participant must be obtained. Examples of events that may, in the 
investigator’s opinion, indicate a lack of clinical benefit include, but are not limited to, 
the following: 


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• Worsening of ECOG PS from baseline by at least 2 points 
• Skeletal related events defined by the following: 
o pathologic bone fracture in the region of cancer involvement 
o cancer related surgery to bone, and/or  
o spinal cord or nerve root compression 
• Development of new CNS metastases 
• Any setting where the initiation of new antineoplastic therapy has been deemed 
beneficial to the participant even in the absence of any such documented clinical 
event. 
See Section 8.1 above for specific requirements when considering continuation of 
treatment.  
8.1.2. 
Study Treatment Restart/Rechallenge 
Study treatment restart or rechallenge is not allowed after liver chemistry stopping 
criteria are met by any participant in this study unless: 
• GSK Medical Governance approval is granted. 
• Ethics and/or IRB approval is obtained, if required, and 
• Separate consent for treatment restart/rechallenge is signed by the participant. 
If GSK Medical Governance approval to restart/rechallenge participant with study 
treatment is not granted, then participant must permanently discontinue study treatment 
and may continue in the study for protocol-specified follow-up assessments. 
Refer to Section 12.10 for additional information. 
8.2. 
Withdrawal from the Study 
• A participant may withdraw from the study at any time at his/her own request, or may 
be withdrawn at any time at the discretion of the investigator for safety, behavioral, 
compliance or administrative reasons. No further assessments will be required and the 
investigator must document this in the site study records. 
• If the participant withdraws consent for disclosure of future information, the Sponsor 
may retain and continue to use any data collected before such a withdrawal of 
consent. 
• If a participant withdraws from the study after providing study samples, GSK will 
retain those samples and any results from sample testing prior to participant 
withdrawal, as described in the informed consent. However, if a participant requests 
destruction of their samples at the time of withdrawal, the investigator should alert 
GSK and document this in the site study records. Once notified, GSK will ensure no 
new testing will be performed on the sample and the sample will be destroyed.  
• A participant will be considered to have withdrawn from the study if the participant 
has not died and is lost to follow-up. 
• Refer to the SoA for data to be collected at the time of study discontinuation and for 
any further evaluations that need to be completed. 


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8.3. 
Lost to Follow-up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. The following actions 
must be taken if a participant fails to return to the clinic for a required study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain if the participant wishes to and/or should 
continue in the study. 
• Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record. 
• Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up.  
9. 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures are summarized in the SoA tables within each arm Appendix (Section 
12.1): Table for Screening assessments, Treatment Period assessments, and Treatment 
Discontinuation Visit [TDV] and Follow-Up assessments. Visit windows, as allowable, 
are notated in the SoA tables.  
9.1. 
General Guidance 
Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct. Protocol waivers or exemptions are not allowed 
except for immediate safety concerns. Therefore, adherence to the study design 
requirements, including those specified in the SoA are essential and required for study 
conduct.  
Immediate safety concerns should be discussed with the Sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue 
study treatment. 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable. 
Procedures conducted as part of another clinical trial within the screening window (e.g. 
imaging studies) and obtained prior to signing of the study informed consent may be used 
for screening/baseline assessments provided the procedures fulfill the protocol defined 
specifications and has been performed within the protocol indicated timeframe. 


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The following points must be noted: 
• 
Informed consent must be signed by a participant before any study required 
procedures are performed. However, procedures conducted as part of the routine 
clinical management (e.g., imaging studies) and conducted prior to signing of the 
study informed consent may be used for screening/baseline assessments provided 
the procedure fulfills the protocol defined specifications and has been performed 
within the protocol indicated timeframe. 
• 
If assessments are scheduled for the same nominal time, then the assessments 
must occur in the following order: 
1. 12-lead ECG 
2. Vital signs 
3. Blood draws 
Note: The timing of the assessments must allow the blood draw to occur at the 
exact nominal time. 
• 
The timing and number of planned study assessments, including safety, biomarker 
or other assessments may be altered during the course of the study based on 
emerging data to ensure appropriate monitoring.  
• 
The change in timing or addition of time points for any planned study assessments 
must be approved by the relevant GSK study team member and then archived in 
the study Sponsor and site study files, but this will not constitute a protocol 
amendment.  
• 
No more than approximately 1375 mL of blood will be collected from each 
participant over the full course of study treatment (2 years). 
9.1.1. 
General Guidance for Treatment Continuity when Participants are 
Unable to Come into the Clinic 
Prior to utilization of any of the measures outlined in this section, discussion and 
approval must be obtained from Sponsor/contract research organization.  
It is expected that sites participating in clinical studies will make every effort to ensure 
proper monitoring and well-being of enrolled participants by adhering to safety 
monitoring as outlined in the SoA (Section 12.1). The use of local laboratories and local 
radiology centers to reduce the need for a participant to come into the clinic is supported, 
if deemed necessary for the well-being of the participant. These local facilities should be 
added to regulatory documents, as required. 
Any restrictions in place at the site that will impact monitoring and/or participant access 
to the site and care providers should be communicated to the Sponsor/contract research 
organization.  
A global telemedicine platform that allows for continued monitoring of AEs, concomitant 
medications, protocol deviations, etc., may be engaged. Discussions around utilization of 


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this technology should be held on a per-site basis, and appropriate documentation of 
utilization should be captured.  
In general, for participants with limited possibility to travel or decreased capacity to come 
to the clinic, replace non-dosing in-person visits with phone contact or alternative 
location for assessment (e.g., local laboratories and imaging centers, at-home collection 
of patient reported outcomes [PROs]).  
9.2. 
Screening and Critical Baseline Assessments 
All screening assessments must be performed within 28 days prior to the first dose unless 
otherwise specified. The ICF may be signed within 45 days prior to first dose. 
The term ‘baseline’ refers to the assessment performed during the screening period prior 
to first dose of study treatment that serves as a comparison or control. For example, the 
baseline laboratory assessment is the laboratory assessment performed prior to first dose.  
Refer to SoA for each arm (Section 12.1) for additional details on assessments required at 
Screening and prior to start of study treatment. All assessments performed must be 
documented in the site source documents. 
The following assessments are required during screening: 
• Demographic parameters such as year of birth and sex will be captured. 
 
• Medical history including cardiovascular medical history, tobacco use, and other risk 
factors will be assessed as related to the inclusion/exclusion criteria.  
• Disease characteristics including medical, surgical, and treatment history including 
radiotherapy, date of initial diagnosis, stage at initial diagnosis according to the 8th 
Edition of TNM for Lung Cancer by the Union for International Cancer Control 
[UICC], histology, tumor genetic/genomic features sand current sites of disease will 
be taken as part of the medical history and disease status. Scans from imaging studies 
performed prior to screening may be requested for assessment of baseline lesions. 
Details concerning prior anticancer therapy (for example, systemic and radiation 
therapy), including best response to prior systemic therapy will be recorded. 
 
• If available, any antibiotic use within 90 days prior to the first dose of study should 
ideally be recorded to help inform the effect of antibiotics on clinical outcome 
through its manipulation of the immune system. 
 
• PD-L1 protein expression by IHC in patients with NSCLC is commonly utilized to 
determine PD-L1 status prior to initiation of treatment with a PD-L1 inhibitor. PD-L1 
expression by IHC and type of assay utilized (i.e., Ventana SP263, Ventana SP142, 
Dako 28-8, or Dako 22C3) must be recorded in the eCRF, if known. 
Baseline lesion assessments required within 28 days prior to the first dose of study 
treatment include: 


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• 
Computed tomography (CT) scan with contrast of the chest and abdomen 
Note: Although a CT scan is preferred, magnetic resonance imaging (MRI) may 
be used as an alternative method of baseline disease assessment, especially for 
those participants where a CT scan is contraindicated due to allergy to contrast, 
provided the method used to document baseline status is used consistently 
throughout study treatment to facilitate direct comparison. When MRI is used for 
disease assessment, a non-contrast CT of the chest should also be performed, to 
evaluate the lungs. Refer to RECIST 1.1 guidelines for use of 
fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT [Eisenhauer, 
2009; Seymour, 2017]. 
• 
MRI of brain with and without IV gadolinium (if clinically indicated) 
• 
Bone scan (if clinically indicated) 
• 
Clinical disease assessment for palpable/visible lesions 
• 
Other areas as indicated by the participant’s underlying disease present prior to 
screening 
Refer to Section 9.3.1 for baseline documentation of target and non-target lesions.  
Safety and laboratory assessments (Section 9.5) required at baseline include: 
• 
Physical examination 
• 
ECOG Performance Status 
• 
Vital Signs 
• 
Concomitant medication 
o Recorded starting from screening through post-study follow-up.  
o Record all medications the participant is taking including prescription 
medications, over-the-counter (OTC) drugs or preparations, and 
herbal preparations including any cannabinoids and/or recreational 
drugs used. 
o At a minimum, the drug name, route of administration, dose, and 
frequency of dosing, along with start and stop dates must be recorded. 
• 
Electrocardiogram 
• 
Echocardiogram 
• 
Laboratory assessments  
9.3. 
Efficacy Assessments 
Planned time points for all efficacy assessments are listed in in each specific arm SoA 
Tables within Section 12.1.  


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9.3.1. 
Tumor Imaging and Disease Assessments 
RECIST 1.1 will be used in the assessment of disease burden (target and non-target 
lesions determination) at Screening and as the primary measure of tumor response 
endpoints.  
Additionally, iRECIST guidelines will be used in the assessment of response/progression 
to account for the unique tumor kinetics observed with immunotherapeutic agents which 
may manifest as an increase in tumor burden then later is followed by regression 
suggesting the apparent observed neoplastic growth representing transient lymphocyte 
infiltration. Following approval by the medical monitor and signed informed consent to 
continue treatment post-progression (Section 8.1), participants with disease progression 
by RECIST version 1.1 guidelines should have a confirmatory disease assessment no 
sooner than 4 weeks after the date disease progression was declared in order to confirm 
disease progression by iRECIST guidelines. The visit level responses and treatment-
based decisions will incorporate iRECIST guidelines [Seymour, 2017].  
Refer to the SoA for each arm (Section 12.1) for the frequency of disease assessments 
post screening. 
A description of the adaptations and iRECIST process is provided in Appendix 12, with 
additional details in the iRECIST publication [Seymour, 2017]. A summary of imaging 
and treatment requirements after first radiologic evidence of progression provided in 
Table 54 and illustrated as a flowchart in Figure 11 in Appendix 12.  
Tumor images will be obtained and transmitted to a central imaging vendor for potential 
central review. The process for tumor imaging and transmission to the central imaging 
vendor are detailed in the Imaging Manual. Tumor imaging is strongly preferred to be 
acquired by IV/oral contrast enhanced CT. For the abdomen and pelvis (if performed), 
contrast-enhanced MRI may be used when CT with iodinated contrast is contraindicated, 
or when mandated by local practice. MRI is the preferred modality for imaging the brain 
and spine. The same imaging modality, ideally the same scanner, scanning technique and 
the use of contrast should be used for a participant throughout the study to optimize 
reproducibility and accuracy of assessment of existing and new tumor burden.  
Notes:  
• Imaging must include the chest and abdomen. 
• Brain imaging should be conducted, if clinically indicated, at Screening and 
throughout the study for evaluation of brain metastases. MRI is preferred 
however CT imaging is acceptable if MRI is medically contraindicated.  
• Bone scans are optional for participants with a history of bone metastases or 
for those participants with new bone pain. Any supplemental imaging done to 
support a positive or negative bone scan, such as plain X-rays that may be 
acquired for correlation, should be submitted to the central imaging vendor.  
All bone scan abnormalities at Screening that could indicate metastases should be 
evaluated by X-ray, CT, or MRI to determine if they represent malignant lesions. If a 
bone scan was performed within 6 weeks prior to the first dose, it does not need to be 


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repeated (in the absence of new or worsening clinical symptoms suggesting bone 
involvement). Typically bone scanning will be performed using bone scintigraphy. 
However, positron emission tomography (PET) scan ([18F]-fluorodeoxyglucose or [18F]-
fluoride) is acceptable, providing coverage is sufficient to evaluate total spine, clavicle, 
ribs, pelvis (if performed) and long bones. 
In the event a photograph is taken of a particular lesion, the site will submit the 
photograph to the central imaging vendor. Refer to the site central imaging vendor 
manual technical requirements for photograph submission.  
9.3.1.1. 
Initial Tumor Imaging 
Initial tumor imaging at Screening must be performed within 28 days prior to first dose. 
Tumor imaging performed as part of routine clinical management is acceptable for use as 
screening tumor imaging if it is of diagnostic quality and performed within 28 days prior 
to first dose and can be assessed by the central imaging vendor.  
9.3.1.2. 
Tumor Imaging During the Study 
The first on-study imaging assessment must be performed 6 weeks after the first dose of 
study treatment. Subsequent tumor imaging must be performed every 6 weeks until Week 
49 and every 12 weeks thereafter. Imaging timing should follow calendar days and 
should not be adjusted for delays in cycle starts. Imaging should continue to be 
performed until disease progression is identified by the investigator.  
Objective response must be confirmed by a repeat imaging assessment. Tumor imaging 
to confirm PR or CR must be performed at least 4 weeks after the first indication of a 
response is observed. Participants will then return to regular scheduled imaging, starting 
with the next scheduled imaging time point. Participants who receive additional imaging 
for confirmation do not need to undergo the next scheduled tumor imaging if it is less 
than 4 weeks later, and tumor imaging may resume at the subsequent scheduled imaging 
time point.  
Per iRECIST (Appendix 12), disease progression should be confirmed by the site at least 
4 weeks and up to 8 weeks after site-assessed first radiologic evidence of PD, following 
approval of treatment continuation by the medical monitor and signed consent by the 
participant. Participants who have unconfirmed disease progression may continue 
treatment at the discretion of the investigator until progression is confirmed by the site, 
provided they have met the conditions detailed in Appendix 12.  
9.3.1.3. 
End of Treatment Imaging 
For participants who discontinue study treatment due to disease progression, tumor 
imaging does not need to be repeated at the TDV. If previous imaging was obtained 
within 6 weeks prior to the date of discontinuation, then imaging at treatment 
discontinuation is not mandatory.  
For participants who discontinue study treatment without documented disease 
progression, every effort should be made to continue monitoring disease status by tumor 


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imaging using the same imaging schedule used while on treatment until the start of a new 
anticancer treatment, disease progression, pregnancy, death, withdrawal of consent, or the 
end of the study, whichever occurs first.  
9.3.2. 
Tumor Growth Kinetics 
To evaluate the effect of study therapy on the growth rate of individual tumor lesions, 
pre-baseline images (within approximately 12 months before the baseline scan; images 
obtained >12 months prior to the baseline scan may also be accepted upon consultation 
with Medical Monitor) will be requested to support exploratory investigation of tumor 
growth kinetics. Up to 3 pre-baseline scans may be requested and submitted to the central 
imaging vendor. Only those participants who consent to this collection will have their 
pre-baseline images submitted to the central vendor for these analyses.  
CT/MRI of the chest and abdomen with IV contrast are preferred, if available, and per 
local standard of practice. The same modality used at study baseline imaging is 
encouraged to be submitted, but not required. If performed, imaging of the brain along 
with any other areas of disease that were imaged in the 6 months prior to baseline scan 
may also be submitted. PET images are not required but may be submitted; and, the CT 
portion (with IV contrast if possible) of a PET/CT examination is acceptable if no other 
CT examinations are available.  
9.3.3. 
Survival Follow-up 
After a participant receives the last dose of study treatment, he or she will enter the 
survival follow-up period. Follow-up for survival and new anticancer therapy (including 
radiotherapy) will occur every 12 weeks until death, completion or termination of the 
overall study, or withdrawal of consent. Follow-up will be conducted via telephone 
contact. 
9.4. 
Adverse Events 
The definitions of AEs and SAEs are provided in Appendix 5. 
The investigator and any designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE and remain responsible for 
following up AEs that are serious, considered related to the study treatment or the study, 
or that caused the participant to discontinue the study treatment (see Section 8). Adverse 
events must be assessed and documented at each patient contact. 
9.4.1. 
Time Period and Frequency for Collecting AE and SAE 
Information 
• 
All AESIs and SAEs will be collected from the start of treatment until 90 days after 
the last dose of study treatment at the time points specified in the SoA (Section 2). 
However, any AESI or SAEs assessed as related to study participation (e.g., study 
treatment, protocol-mandated procedures, invasive tests, or change in existing 
therapy) or related to a GSK product will be recorded from the time a participant 
consents to participate in the study. If subsequent anti-cancer treatment is initiated 


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during the 90-day follow-up period yet <30 days after the date study treatment was 
discontinued, AESI and SAEs must continue to be collected until 30 days after last 
dose of study treatment and documentation of the subsequent anticancer treatment 
will be recorded in the eCRF. 
• 
All AEs will be collected from the start of study treatment until 30 days after the last 
dose of study treatment at the time points specified in the SoA (Section 2). 
• 
Medical occurrences that begin before the start of study treatment but after obtaining 
informed consent will be recorded in the Medical History/Current Medical 
Conditions section of the CRF and not in the AE section. 
• 
All SAEs will be recorded and reported to the Sponsor or designee immediately and 
under no circumstance should this exceed 24 hours, as indicated in Appendix 5. The 
investigator will submit any updated SAE data to the Sponsor within 24 hours of it 
being available. 
• 
Investigators are not obligated to actively seek AEs or SAEs in former study 
participants. However, if the investigator learns of any SAE, including a death, at 
any time after a participant has been discharged from the study, and he/she considers 
the event to be reasonably related to the study treatment or study participation, the 
investigator must promptly notify the Sponsor. 
• 
The method of recording, evaluating, and assessing causality of AEs and SAEs and 
the procedures for completing and transmitting SAE reports are provided in 
Appendix 5. 
9.4.2. 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AE and/or SAE. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrence.  
9.4.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs and non-serious AESIs (Section 7.2.1 
and Section 9.4.1), will be followed until the event is resolved, stabilized, otherwise 
explained, or the participant is lost to follow-up (as defined in Section 8.3). If subsequent 
anti-cancer treatment is initiated during the 90-day follow-up period yet <30 days after 
the date study treatment was discontinued, AESI and SAEs must continue to be collected 
until 30 days after last dose of study treatment and documentation of the subsequent 
anticancer treatment will be recorded in the eCRF. Further information on follow-up 
procedures is given in Appendix 5.  
9.4.4. 
Regulatory Reporting Requirements for SAEs 
• 
Prompt notification by the investigator to the Sponsor of a SAE is essential so 
that legal obligations and ethical responsibilities toward the safety of 
participants and the safety of a study treatment under clinical investigation are 
met.  


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• 
The Sponsor has a legal responsibility to notify both the local regulatory 
authority and other regulatory agencies about the safety of a study treatment 
under clinical investigation. The Sponsor will comply with country-specific 
regulatory requirements relating to safety reporting to the regulatory authority, 
Institutional Review Boards (IRB)/Independent Ethics Committees (IEC), and 
investigators. 
• 
Investigator safety reports must be prepared for suspected unexpected serious 
adverse reactions (SUSAR) according to local regulatory requirements and 
Sponsor policy and forwarded to investigators as necessary. 
• 
An investigator who receives an investigator safety report describing a SAE or 
other specific safety information (e.g., summary or listing of SAE) from the 
Sponsor will review and then file it along with the Investigator’s Brochure and 
will notify the IRB/IEC, if appropriate according to local requirements. 
 
9.4.5. 
Cardiovascular and Death Events 
For any cardiovascular events detailed in Appendix 5 and all deaths, if they are 
considered SAEs, specific cardiovascular and death sections of the eCRF will be required 
to be completed. These sections include questions regarding cardiovascular (including 
sudden cardiac death) and non-cardiovascular death.  
The CV (cardiovascular) eCRFs are presented as queries in response to reporting of 
certain cardiovascular MedDRA terms. The cardiovascular information should be 
recorded in the specific cardiovascular section of the eCRF within 1 week of receipt of a 
cardiovascular event data query prompting its completion.  
The death eCRF is provided immediately after the occurrence or outcome of death is 
reported. Initial and follow-up reports regarding death must be completed within one 
week of when the death is reported. 
9.4.6. 
Pregnancy 
• 
Details of all pregnancies in female participants and female partners of male 
participants will be collected after the start of study treatment and until 120 days 
after the last dose of study treatment. For participants randomized to the SoC only 
arm, pregnancy details with be collected after the start of study treatment and until at 
least 3 days after the last dose of study treatment (or per institutional standard). 
• 
If a pregnancy is reported, the investigator should inform GSK within 24 hours of 
learning of the pregnancy and should follow the procedures outlined in Section 9.4.4. 
• 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAE. 
9.5. 
Safety Assessments 
Planned time points for safety assessments are provided within each arm SoA Appendix 
(Section 12.1). Additional time points for safety testing may be added during the study 


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based on newly available data to ensure appropriate safety monitoring. PK and ADA 
samples will also be collected for safety. See Section 9.6 and Section 9.7 for additional 
information. 
9.5.1. 
Physical Examinations 
• A complete physical examination performed at Screening will include, at a 
minimum, assessment of the cardiovascular, respiratory, gastrointestinal, skin and 
neurological systems.  
• A brief physical examination performed at each subsequent visit (refer to SoA 
tables for each arm in Section 12.1), will include, at a minimum, assessments of 
the skin, lungs, cardiovascular system, and abdomen (liver and spleen).  
• Investigators should pay special attention to clinical signs related to previous 
serious illnesses. 
• Physical examinations may be performed within one day of dosing (i.e., as 
opposed to the day of dosing), if necessary. 
9.5.2. 
Performance Status 
Performance status will be assessed using the ECOG scale at each visit, on the day of 
treatment or within 24 hours prior to dosing, if necessary (Appendix 8). 
9.5.3. 
Vital Signs 
• Vital signs will be measured after 5 minutes of rest and will include temperature, 
systolic and diastolic blood pressure, pulse rate, respiratory rate, and oxygen 
saturation (measured by pulse oximetry). Blood pressure should be taken in the 
same position throughout the study and captured in the eCRF.  
• Vital signs will be measured more frequently if warranted by clinical condition of 
the participant.  
• On days where vital signs are measured multiple times, temperature does not need 
to be repeated unless clinically indicated. 
• If a participant develops fever and infusion related reaction or cytokine release 
syndrome is suspected, refer to management guidelines (Section 7.2.1). 
• Height will be recorded at Screening only. 
• Weight will be measured and recorded (in kilograms) at baseline and every other 
treatment visit.  
• Vital signs must be recorded prior to dosing on treatment days. 
9.5.4. 
Electrocardiograms 
A 12-lead ECG will be obtained at screening using an ECG machine that automatically 
calculates the heart rate and measures PR, QRS, QT, and QTcF intervals; manual 
calculation of QTcF is permitted. ECGs may be repeated during the study as clinically 
indicated, unless noted otherwise in the SoA for each arm under Section 12.1.   


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9.5.5. 
Echocardiogram 
Echocardiograms (ECHO) will be performed locally at baseline to assess cardiac ejection 
fraction for study eligibility, as specified in the SoA (Section 12.1). Additional ECHO 
assessments may be performed if clinically warranted. The evaluation of the 
echocardiography should include an evaluation for LVEF and both right and left-sided 
valvular lesions. Multigated Acquisition Scan (MUGA) can be used in lieu of ECHO (if 
not feasible) in the assessment of LVEF; the same modality should be used in any 
subsequent assessments. 
9.5.6. 
Clinical Safety Laboratory Assessments 
Refer to Appendix 3 for the list of clinical laboratory tests to be performed and to the 
SoA for each arm (Section 12.1) for the timing and frequency.  
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF. The 
laboratory reports must be filed with the source documents. Clinically significant 
abnormal laboratory findings are those which are not associated with the underlying 
disease, unless judged by the investigator to be more severe than expected for the 
participant's condition. 
All protocol required safety laboratory assessments, as defined in Table 51 must be 
conducted in accordance with the SoA for each arm. Reference ranges for all safety 
parameters must be provided to the site by the laboratory responsible for the assessments. 
All study-required safety laboratory assessments will be performed at the institution’s 
local laboratory. Laboratory safety assessments required prior to dosing may be 
performed up to 3 days prior to dosing, if necessary. The results of each test must be 
recorded in the eCRF. If additional non-protocol specified laboratory assessments are 
performed at the institution’s local laboratory and result in a change in participant 
management or are considered clinically significant by the investigator (for example, 
SAE or AE or dose modification) the results must also be recorded in the eCRF. 
For all other protocol required blood and tissue sample collections, laboratory requisition 
forms must be completed, and samples must be clearly labeled with the participant 
number, protocol number, site/center number, and visit date. Details for the preparation 
and shipment of samples that are required to be tested by a central laboratory will be 
provided by the laboratory and are detailed in the laboratory manual. 
Refer to the SRM for appropriate processing and handling of samples to avoid duplicate 
and/or additional blood draws. 
All laboratory tests with values that are considered clinically significantly abnormal 
during participation in the study or within 30 days after the last dose of study treatment 
must 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 must be 
identified, and the Sponsor notified. 


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9.6. 
Pharmacokinetics  
Planned time points for all pharmacokinetics assessments are listed in the SoA for each 
arm (Section 12.1).  
9.6.1. 
Blood Sample Collection 
Blood samples for PK analysis are to be collected as indicated in the SoA. The actual 
date and time of each blood sample collection will be recorded. The timing of PK 
samples may be altered and/or PK samples may be obtained at additional time points to 
ensure adequate PK monitoring. 
Details on PK blood sample collection, processing, storage, and shipping procedures are 
provided in the SRM/laboratory manual. If additional study drugs are added to this study 
for which PK samples are required, details will be provided in the SRM. 
9.6.2. 
Sample Analysis 
PK analysis will be performed for participants as indicated in each SoA. Concentrations 
of the study treatments will be determined using validated bioanalytical methodologies. 
Once the analysis has been completed, for any remaining samples may be analyzed for 
other compound-related metabolites. Refer to the SRM for further details. 
9.7. 
Anti-Drug Antibodies 
The actual date and time of each blood sample collection will be recorded for each 
specific analyte. Details of blood sample collection (including volume to be collected), 
processing, storage, and shipping procedures are provided in the SRM. 
The timing and number of planned immunogenicity samples may be altered during the 
course of the study, based on newly-available data to ensure appropriate safety 
monitoring. In the event of a hypersensitivity reaction that is either clinically significant 
in the opinion of the investigator, or leads to the participant withdrawing from the study 
treatment, blood samples must be taken from the participant for immunogenicity testing 
at the timepoints indicated in the arm specific SoAs (Section 12.1).  
9.8. 
Genetics 
Planned time points for all genetics-related assessments are listed in in the SoA for each 
arm (Section 12.1). 
A whole blood sample for DNA isolation will be collected from participants who have 
consented to participate in the genetics analysis component of the study. Participation is 
optional. Participants who do not wish to participate in the genetic research may still 
participate in the study. 
In the event of DNA extraction failure, a replacement genetic blood sample may be 
requested from the participant. Signed informed consent will be required to obtain a 
replacement sample unless it was included in the original consent. 


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See Appendix 7 for further information regarding genetic research. Details on processes 
for collection and shipment and destruction of these samples can be found in the SRM. 
9.9. 
Biomarkers 
Planned time points for all biomarker assessments are listed in the SoA for each arm 
(Section 12.1). 
9.9.2. 
Tumor Tissue 
9.9.2.1. 
Screening Biopsies 
Part 1: All participants are required to provide fresh tumor tissue AND archival tumor 
tissue samples at screening prior to start of study treatment, unless specified otherwise in 
the SoA of each regimen in the respective subsections under Section 12.1.  
Part 2: Tumor tissue at screening (either archival or fresh biopsy if archival tissue is 
unavailable) is required for all participants in Part 2. Fresh tumor tissue AND an archival 
tissue sample obtained during screening are required for at least 20 participants for each 
arm.  
Participants with inaccessible tumor or those participants that do not consent to the tumor 
biopsy procedure may be enrolled provided an archival specimen is submitted. However, 
no participant will be allowed on study without either an archival specimen OR a fresh 
biopsy. The archival specimen may have been obtained at any time from the time of 
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initial diagnosis to time of study entry. Sufficient and evaluable tumor tissue for protocol 
specified testing needs to be provided (reference SRM for more details). 
9.9.2.2. 
On-Treatment Biopsies 
Part 1: All participants are required to provide paired fresh biopsies at screening and on-
treatment at week 7 (± 8 days), unless specified otherwise in the SoA of each regimen in 
the respective subsections under Section 12.1.  
Part 2: Fresh biopsy collected at week 7 (± 8 days) is optional for participants in Part 2, if 
tumor is amenable to biopsy and upon participant’s consent; However, paired fresh tumor 
biopsies collected at screening and week 7 (± 8 days) is required for at least 20 
participants for each arm. 
Enrollment may become limited during the study, as required, to ensure collection of 
fresh tissue samples as noted. 
 
Additional optional fresh tumor tissue sample will be collected at Week 19 (± 8 days) at 
the time of imaging assessment and/or at the time of confirmed PR or PD, upon 
participant consent (± 8 days).  
When feasible, tumor imaging should be completed prior to tissue collection to avoid 
potential radiographic alterations due to the biopsy procedure. 
 
These tissues will be evaluated by IHC or other potential methods, including image 
analysis, for expression of phenotypic and functional immune cell markers on tumor 
infiltrating lymphocytes (TIL) and other immune cells as well as immune signaling 
markers on tumor cells to understand the anti-tumor responses. In addition, when 
possible, similar analyses will be performed on tumor tissue obtained upon progression. 
Additionally, tumor tissue may be sequenced to assess T-cell diversity (TCR diversity) as 
well as evaluated for any DNA/RNA/protein changes correlating with response, 
including tumor mutational load assessments. These samples may also be evaluated for 
predictive measures of response to include in the biomarker selected population. If a 
predictive biomarker is identified, these tissues may be used for the development of a 
diagnostic test.  
Other biomarkers may be evaluated as determined by additional data. Details for the 
samples collection, processing, storage, and shipment will be provided in the SRM. 
9.10. 
Patient-Reported Outcome Assessments 
CCI


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CCI


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Table 6 
PRO Outcomes Assessed in Study 205801 
Instrument  
Role 
Rationale & Overview 
CCI
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CCI
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10. 
STATISTICAL CONSIDERATIONS  
10.1. 
Primary Endpoint 
10.1.1. 
Primary Endpoint: Part 1 
The primary endpoint for Part 1 is the incidence of AEs, SAEs, DLTs, changes in 
safety/laboratory assessment parameters, and dose modifications.  
A key secondary endpoint for Part 1 is Objective Response Rate (ORR) using RECIST 
1.1 by investigator assessment. ORR is defined as the percentage of participants with a 
best overall response of CR or PR at any time. 
10.1.2. 
Primary Endpoint: Part 2 
The primary endpoint for Part 2 is OS. OS is defined as the interval from date of 
randomization to the date of death, irrespective of the cause of death. If a participant does 
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not have a documented date of death or is lost to follow-up, time of death will be 
censored at the date of last contact. 
10.2. 
Hypothesis 
10.2.1. 
Hypothesis: Part 1 
The primary objective of Part 1 is to establish the safety and tolerability of the 
experimental combination regimen of each arm.  
10.2.2. 
Hypothesis: Part 2 
The primary objective of Part 2 is to determine whether the experimental arms prolong 
overall survival relative to standard of care. The null hypothesis is that there is no 
difference in overall survival between each experimental arm and the SoC and alternative 
hypothesis is that the experimental regimen improves overall survival over the SoC. The 
predictive probability inference approach will be used as the basis for both interim and 
final decision making. The predictive probability of success (PoS) in future Phase 3 study 
(phase 3 success being defined as a statistically significant log-rank test with 1-sided 
alpha=0.025) will be calculated as a measure of the improvement in OS in the 
experimental arm compared with the SoC arm. A cutoff of 43% or greater for the PoS of 
future Phase 3 study, approximately corresponding to an observed HR no greater than 0.8 
in a substudy, will be implemented as the criteria for an experimental regimen to be 
considered for proceeding to Part 2. As this is a signal finding study and not 
confirmatory, each experimental arm will be compared to control in a pairwise fashion 
with no adjustment for multiple comparisons. 
10.3. 
Sample Size Determination 
10.3.1. 
Sample Size: Part 1 
For Part 1, sample size will be defined for each regimen under the corresponding 
appendix in Section 12.1.   
The FDA approved dose of docetaxel provides the following outcomes, based on the 
validated data.  
  
Study 
  
TAX 317 
Control for 317 
TAX320 
Control for 320 
  
Docetaxel 75 
mg/m2 n=55  
Best Supportive 
Care n=49  
Docetaxel 75 
mg/m2 n=125  
Vinorelbine or 
Ifosfamide n=123  
95% CI (Risk Ratio) 
(0.35, 0.88) 
(0.63, 1.06) 
Median Survival  
(95% CI) 
7.5 months  
(5.5, 12.8) 
4.6 months  
(3.7, 6.1) 
5.7 months  
(5.1, 7.1) 
5.6 months  
(4.4, 7.9) 


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Study 
  
TAX 317 
Control for 317 
TAX320 
Control for 320 
  
Docetaxel 75 
mg/m2 n=55  
Best Supportive 
Care n=49  
Docetaxel 75 
mg/m2 n=125  
Vinorelbine or 
Ifosfamide n=123  
% 1-year Survival  
(95% CI) 
37% (24, 50) 
12% (2, 23) 
30% (22, 39) 
20% (13, 27) 
Time to Progression  
(95% CI) 
12.3 weeks 
(9.0, 18.3) 
7.0 weeks  
(6.0, 9.3) 
8.3 weeks  
(7.0, 11.7) 
7.6 weeks  
(6.7, 10.1) 
Response Rate  
(95% CI) 
5.5%  
(1.1, 15.1) 
N/A 
5.7%  
(2.3, 11.3) 
0.8%  
(0.0, 4.5) 
 
Additional information is available from the control arm of the FDA approved label for 
pembrolizumab where docetaxel was used as a control. The following table summarize 
those data. 
Endpoint 
 Docetaxel 75 mg/m2 every 3 weeks n=152 
OS Deaths (%) 
86 (57%) 
OS Median in months 
8.2 (6.4, 10.7) 
PFS Events 
118 (78%) 
PFS Median in months 
4.1 (3.6, 4.3) 
ORR 
8% (4, 13) 
Median duration of response in months (range) 
8.1 (2.1+, 8.8+) 
 
Examining the confidence intervals for docetaxel response rates across not only the FDA 
approved package inserts, but other published studies show that while the point estimates 
for response rate may vary, the 95% Confidence Intervals around the point estimates 
remain in the 5%-15% range. Consequently, using a 10% Response Rate as a benchmark 
is reasonable based on available data. Data from 205801 platform study Substudy 1, if 
available, may be used to calibrate this assumption of the docetaxel monotherapy 
response rate for the futility analysis. 
 


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10.3.2. 
Sample Size: Part 2 
In Part 2, 70 participants in each experimental arm and a minimum of 35 participants in 
the SoC arm will be randomized. Sample size and associated operating characteristics 
were evaluated via simulation.  
The 8-month milestone survival in the SoC arm is estimated to be ~40% in squamous cell 
lung cancer (Brahmer, 2015), ~60% in non-squamous lung cancer (Borghaei, 2015), and 
~50% in PD-L1 positive population (Herbst, 2016). The participant population in the 
current study is expected to be a mixed population with both squamous and non-
squamous lung cancer participants; therefore, mean target rate is assumed to be ~50% 
(Figure 4). 
For the target effect of experimental regimens, there is a potential delayed effect at 
treatment start and sustained effect after prolonged follow-up (Brahmer, 2015; Borghaei, 
2015). The survival probability in these arms is expected to overlap in the SoC arm for up 
to 4 months from start of treatment followed by a separation. It is hypothesized that 
percentage of surviving participants is maintained at 20% after 24 months (Figure 4).  
Under the alternative hypothesis three-piece piecewise Weibull distributions are used to 
describe the survival distribution of each experimental arm and two-piece piecewise 
Weibull distributions are used to describe the survival curve of docetaxel (Refer to 
Appendix 13 for simulation parameters). Details of the piecewise Weibull model are 
provided in the statistical appendix (Section 12.13). Using this modeling approach for the 
primary endpoint of OS, the assumed survival curve for the SoC arm is presented using 
blue dashes and the target survival curve for the experimental arm is presented as the 
solid red curve in Figure 4. Based on these two curves, the hazard ratio is approximately 
0.58.      
Sample size was chosen by simulating the entire platform in which 4 experimental arms 
enter the master protocol at different points in time. Enrollment of 9 participants per 
month is assumed. Interim and final analyses are performed based on predetermined 
decision rules as specified in Section 10.3.3 and Section 10.5.1, respectively.  The 
planned Phase 3 sample size is 300 (150 participants per arm and a total of 210 events).  
The future phase 3 trial will use the log-rank (frequentist) test and the decision rule at 
interim and end of phase 2 will use the (Bayesian) predictive probability, given the 
results in phase 2, that the future log-rank test in phase 3 study will be significant, thus, 
resulting in a methodology that is a mixture of Bayesian and frequentist. Simulations 
assess the Operating Characteristics of the predictive probability decision criteria under 
the null and alternative hypotheses, as described in Section 10.3.4. A cutoff of 43% or 
greater for the PoS of future phase 3 study, approximately corresponding to an observed 
HR ≤ 0.8 for each substudy, is used as a guide for future development of each 
experimental arm. Sample size was calculated under the simulated survival curves shown 
in Figure 4.  
The final analysis of OS for a substudy will be performed when approximately 85 death 
events have occurred in the experimental arm and SoC arm combined, and the last 
participant in that substudy has been randomized for at least 6 months. In the case death 
events occur at a rate lower than expected due to potentially prolonged survival benefit, 


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to avoid substantial delay of final analysis for a substudy, the primary analysis for a 
substudy may be conducted once approximately 75 events have occurred and the last 
participant in that substudy has been randomized for at least 6 months, at the discretion of 
the Sponsor. A minimum of 35 events are needed from the experimental arm for both 
primary and final analysis. 
Assuming the true HR≈0.58, 85 death events will provide 94.2% probability (power) of 
achieving the guidance criteria with future phase 3 study success ≥ 43%. In the case of 
primary analysis being performed with 75 death events, it will provide 88.3% probability 
of achieving the guidance criteria. If the true HR is 1, 85 and 75 death events will have 
16.6% and 18.2% Type I error, respectively. 
Figure 4 
Assumed Survival Probability Under Alternative Hypothesis in 
Experimental Regimens (Red) and  
Docetaxel (Blue) 
 
 
10.3.3. 
Interim Analyses 
10.3.3.1. 
Interim Analyses: Part 1 
An interim evaluation of futility in terms of ORR may be conducted for an arm if data 
permits. Details for futility analyses are provided in the respective subsection for each 
arm in Appendix Section 12.1.  
 


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10.3.3.2. 
Interim Analyses: Part 2 
This is a platform study utilizing a master protocol designed so that additional 
experimental arms may enter and leave the trial at different time points as determined by 
pre-specified decision criteria.  
Part 2 of the study will be conducted under the auspices of an IDMC and steering 
committee. The membership and activities are outlined in the IDMC and steering 
committee charters. This committee will review all available interim safety and efficacy 
data as the study progresses. Interim analyses will be performed approximately every 6 
months depending on the amount of additional data accrued.   
Interim Analyses for OS 
An interim analysis of OS will be conducted for each substudy after approximately 45 
events (experimental arm and SoC combined) and a minimum of 18 events from 
experimental arm have been observed. Note, events from the SoC arm will be counted 
from the initial study start (i.e. SoC events from substudy 1 will be counted with any 
further events observed in subsequent substudies). Stopping guidelines will be provided 
as part of the IDMC charter. Final decisions on termination of an arm will be based on 
the totality of the data. 
Final analysis for Graduation  
The final analysis for each substudy will occur after observing 85 events (experimental 
regimen and SoC combined) and the last participant in a substudy has been randomized 
for at least 6 months. A minimum of 35 events are needed from the experimental arm for 
the final analysis of that substudy. In the case of death events occur at a rate slower than 
expected due to potentially prolonged survival benefit, to avoid substantial delay of final 
analysis for a substudy, primary analysis for a substudy may be conducted once 
approximately 75 events have occurred and at least 35 events observed in the 
experimental arm, and the last participant in that substudy has been randomized for at 
least 6 months, at the discretion of the Sponsor. A cutoff of 43% or greater for the PoS of 
future phase 3 study is used as graduation criteria for an experimental regimen to be 
considered for proceeding to Part 2. The final decision of proceeding to Part 2 will be 
based on the totality of data. An experimental regimen may be discontinued at any time 
due to safety concerns. 
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10.3.4. 
Statistical Operating Characteristics 
For Part 1, please see details under the corresponding appendix for each arm in Section 
12.1.  
For Part 2, simulations were carried out to determine the operating characteristics for the 
primary comparisons for Part 2. The simulation results are presented in Table 7 and Table 
8. Since the randomization ratios for subsequent studies range from 1:4 to 1:2 (as shown 
in Table 1), the simulations for subsequent studies were performed for both 1:4 and 1:2 
scenarios. Table 7 shows simulation results for 85 events at final analysis as planned and 
Table 8 shows simulation results for the primary analysis with 75 events in the case 
primary analysis is decided to be conducted.  
The simulations on OS are based on the following assumptions: 
1. 
The sample size for the experimental arm is 70 for all substudies. The 
sample size for the control arm is 35 for substudy 1, and for subsequent 
studies it follows dynamic randomization ratios as described in Table 1.  
2. 
The required minimum number of death events in the experimental arm 
are 18 for the interim analysis and 35 for the final (or primary) analysis. 
3. 
The survival curve for the SoC arm and the experimental arm are assumed 
to be same as presented in Figure 4, with target HR≈0.58. The Weibull 
parameters of each curve used for the simulations are detailed in Section 
12.13.1. 
4. 
The recruitment rate is approximately 9 participants per month. 
5. 
The start date of Part 2 of subsequent studies is ~34 months after the start 
date of substudy 1. 
6. 
The futility threshold for interim analysis is 5% or less for the PoS of 
future phase 3 study , as described in Appendix C of the IDMC charter.  
7. 
A cutoff of 43% or greater for the PoS of future phase 3 study is used as 
graduation criteria for each experimental arm. 
It is noted that the simulations were performed for single substudy scenario instead of 
multiple experimental arms randomized concurrently. Although concurrent 
randomization may potentially affect the enrolment speed, since substudies are event 
driven, it is not expected to lead to substantial change of the operating characteristics 
except for timing of interim and final analysis.  


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Table 7 
Statistical Operating Characteristics for Target Effect (HR ≈ 0.58) and 
Null Effect (HR=1) for 85 Events at Interim and Final Analysis  
Treatment 
Effect 
Scenarios 
Substudies 
Number of Participants in 
SoC Arm 
Interim Analysis of OS 
Final Analysis (85 events) 
Participants 
from 
Substudy 1 
Participants 
from 
Subsequent 
Substudy 
Average 
Events 
Prob. of 
Futility 
Average 
Events 
Power or 
Type I error 
(Pred. 
prob.≥43%) 
SoC 
Trt 
SoC 
Trt 
HR ~ 0.58 
Substudy 1 
35 
NA 
17.4 
27.6 
3.4% 
33.1 
51.9 
94.2% 
Subsequent 
substudy 
(ratio 1:4) 
35 
18 
40.8 
18 
9.3% 
47.8 
37.3 
81.9% 
Subsequent 
substudy 
(ratio 1:2) 
35 
35 
46.1 
18 
9.2% 
58.4 
35 
76.3% 
HR =1 
Substudy 1 
35 
NA 
15 
30 
19.0% 
28.3 
56.7 
16.6% 
Subsequent 
substudy 
(ratio 1:4) 
35 
18 
39.9 
18 
22.6% 
45.3 
39.7 
14.9% 
Subsequent 
substudy 
(ratio 1:2) 
35 
35 
44.5 
18 
22.0% 
53 
35.4 
15.6% 
Note: The simulation did not incorporate the minimum requirement of 6 months from randomization date of the last 
participant to analysis date.  
Table 8 
Statistical Operating Characteristics for Target Effect (HR ≈ 0.58) and 
Null Effect (HR=1) for 75 Events at Primary Analysis 
Treatment 
Effect 
Scenarios 
Substudies 
Number of Participants in SoC 
Arm 
Primary Analysis (75 events) 
Participants 
from Substudy 
1 
Participants 
from 
Subsequent 
Substudy 
Average Events 
Power or 
Type I error 
(Pred. 
prob.≥43%) 
SoC 
Trt 
HR ~ 0.58 
Substudy 1 
35 
NA 
29.8 
45.2 
88.3% 
Subsequent substudy 
(ratio 1:4) 
35 
18 
47 
35 
76.7% 
Subsequent substudy 
(ratio 1:2) 
35 
35 
58.4 
35 
76.3% 
HR =1 
Substudy 1 
35 
NA 
25 
50 
18.2% 
Subsequent substudy 
(ratio 1:4) 
35 
18 
44.2 
35 
16.2% 
Subsequent substudy 
(ratio 1:2) 
35 
35 
52.8 
35 
15.6% 
Note: The simulation did not incorporate the minimum requirement of 6 months from randomization date of the last 
participant to analysis date.  
 


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10.3.5. 
Sample Size Sensitivity 
It is expected that the statistical operating characteristics will be dependent on 
assumptions around target treatment effects and survival curve of SoC. Evaluations of 
sensitivity analysis were performed varying one assumption at a time (See Table 9, Table 
10, Figure 5, and Figure 6). Sensitivity analysis with respect to HR was conducted using 
simulations under two scenarios: HR=0.48 and HR=0.70. For the case where HR=0.48, 
the target survival curve for the experimental arm is presented in Figure 6A using the 
thick solid orange curve and the assumed survival curve for SOC is presented using blue 
dashes. For the case where the HR=0.70, the target survival curve for the experimental 
arm in Figure 6B is presented using the thick solid green curve and the assumed survival 
curve for SOC is presented using blue dashes. The experimental target survival curve 
(with HR=0.58 relative to SOC) is also presented (with notation) in both figures. 
Sensitivity analysis simulation results showing the operating characteristics of the 
predictive probability decision criteria under these 2 scenarios (HR=0.48 and HR=0.70) 
are presented in Table 9. 
Table 9 
Sensitivity Analysis to Evaluate the Assumption of Treatment 
Effects  
Treatment 
Effect 
Scenarios 
Substudies 
Number of Participants in 
SoC 
Interim Analysis of OS 
Final Analysis (85 events) 
Participants 
from 
Substudy 1 
Participants 
from 
Subsequent 
Substudy 
Average 
Events 
Prob. of 
Futility 
Average 
Events 
Overall Power 
(Pred. 
prob.≥43%) 
SoC 
Trt 
SoC 
Trt 
Greater 
than 
Target 
Effect 
(HR ≈ 
0.48)1 
Substudy 1 
35 
NA 
18.3 
26.7 
1.8% 
34.3 
50.7 
99.2% 
Subsequent 
substudy 
(ratio 1:4) 
35 
18 
41.1 
18 
6.6% 
48.9 
36.4 
93.9% 
Subsequent 
substudy 
(ratio 1:2) 
35 
35 
46.9 
18 
6.5% 
61.1 
35 
90.0% 
Lower 
than 
Target 
Effect 
(HR ≈ 
0.7)2 
Substudy 1 
35 
NA 
16.6 
28.4 
6.3% 
31.6 
53.4 
76.8% 
Subsequent 
substudy 
(ratio 1:4) 
35 
18 
40.4 
18 
12.6% 
46.9 
38.2 
61.7% 
Subsequent 
substudy 
(ratio 1:2) 
35 
35 
45.5 
18 
13.0% 
56.2 
35.1 
56.3% 
1 Greater than target effect as shown in Figure 6A (Solid Orange Curve). 
2 Lower than Target effect as shown in Figure 6B (Solid Green Curve). 
Note: The simulation did not incorporate the minimum requirement of 6 months from randomization date of the last 
participant to analysis date.  


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Sample size sensitivity analysis is also performed assuming higher survival probability of 
SoC, while the survival probability of experimental arm does not change. The simulation 
results are presented in Table 10. 
 
Table 10 
Sensitivity Analysis with Higher Survival Probability in SoC (median 
survival = 9 months as described in solid blue line in Figure 5) 
Substudies 
Number of Participants in 
SoC Arm 
Interim Analysis of OS 
Final Analysis (85 events) 
Participants 
from 
Substudy 1 
Participants 
from 
Subsequent 
Substudy 
Average Events 
Prob. of 
Futility 
Average Events 
Power or Type I 
error (Pred. 
prob.≥43%) 
SoC 
Trt 
SoC 
Trt 
Substudy 1 
35 
NA 
16.7 
28.3 
5.9% 
32.3 
52.7 
83.8% 
Subsequent 
substudy 
(ratio 1:4) 
35 
18 
40.4 
18 
12.8% 
47.1 
37.9 
66.1% 
Subsequent 
substudy 
(ratio 1:2) 
35 
35 
45.5 
18 
12.2% 
56.8 
35.1 
61.0% 
Note: The simulation did not incorporate the minimum requirement of 6 months from randomization date of the last 
participant to analysis date. 
 
Figure 5 
Survival of SoC (solid blue line) is Higher than Target Survival of 
SoC (dotted blue line) 
 


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Figure 6 
Survival Curves of Experimental Arms in Greater Than Expected 
Survival (A: Orange Solid Line) and Less Than Expected Survival (B: 
Green Solid Line) 
 
10.3.6. 
Sample Size Re-estimation 
Sample size re-estimation is not planned for this study. 
10.4. 
Populations for Analyses 
For analysis purposes, the following populations are defined: 
The Intent to Treat Population (ITT) is defined as all participants who were 
randomized to treatment regardless of whether the participants actually received study 
treatment. All efficacy endpoints will be evaluated based on this population.  
The Safety Population is defined as all participants who receive at least 1 dose of SoC or 
experimental regimen based on actual treatment received. All safety endpoints will be 
evaluated based on this population.  
The PK Population will consist of all participants from the ITT Population from whom a 
blood sample is obtained and analyzed for PK concentration.  
DLT-evaluable participants are defined as all participants who take at least 1 dose of 
study intervention and are followed for the DLT observation period or are withdrawn 
within the DLT observation period due to meeting the DLT criteria and no 
resolution/recovery per dose modifications and toxicity management guidelines. (Note: 
participants enrolled in a PK/PD cohort at a previously cleared dose will not be included 
in the DLT evaluable population). 


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10.5. 
Statistical Analyses 
This is a platform study utilizing a master protocol with different arms for each 
experimental regimen(s), the statistical analyses will be conducted separately for each 
arm. Data will be listed and summarized according to the GSK reporting standards, 
where applicable. Complete details of the analysis will be documented in the Reporting 
and Analysis Plan (RAP). Any changes to the analysis plan described in this protocol will 
be documented in the RAP and final clinical study report (CSR).  
10.5.1. 
Analysis 
10.5.1.1. 
Part 1 Analysis 
The primary objective of Part 1 is to establish the safety and tolerability of experimental 
regimens prior to transition to Part 2 of the study.  
 
Safety and tolerability will be guided using the methodology and associated dose decision 
rule as described in the respective subsection for each substudy in Appendix Section 
12.1. However, to ensure safety of participants, dose recommendations based on the 
statistical methodology can be overridden at the discretion of the Medical Monitor, 
especially in the event of DLT. 
 
10.5.1.2. 
Part 2 Primary Efficacy Analysis 
The primary endpoint for Part 2 is OS. The primary analysis is HR and its 95% 
confidence interval from the Cox model with a single treatment covariate. The PoS of 
future phase 3 study will also be reported. A cutoff of 43% or greater for the PoS of 
future phase 3 study is used as a guide for future development of each experimental arm. 
The theorem and details for the calculation of PoS are provided in Appendix Section 
12.13.2. 
10.5.1.2.1. Sensitivity Analysis 
To evaluate the exchangeability assumption between non-concurrent and concurrent SoC 
data, sensitivity analyses will be conducted to evaluate time-dependency in the SoC arm. 
The exchangeability assumption will be examined by comparing overall survival between 
non-concurrent and concurrent SoC data, by using Cox’s proportional hazard model with 
indicator in control data (0: nonconcurrent, 1: concurrent data) as a covariate. If there is a 
difference in OS between non-concurrent and concurrent SoC, this difference will be 
further investigated or examined. Sensitivity analysis will be conducted if there is 
evidence of a violation of the exchangeability assumption. An example of a sensitivity 
analysis is one where only the concurrent data will be included (i.e., no non-concurrent 
data are used) in evaluating the treatment effect of the experimental regimen at data 
analysis.  


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10.5.1.3. 
Key Secondary Endpoint 
The key secondary endpoints are the milestone survival rates at 12 and 18 months, which 
will be estimated using the Kaplan-Meier method. The milestone survival and the 
differences between the experimental arm and SoC will be presented. The details of the 
analysis will be further discussed in RAP.  
10.5.2. 
Other Secondary Analyses 
10.5.2.1. 
Anticancer Activity Analyses 
The ITT Population will be used for anticancer activity analyses. Anticancer activity will 
be evaluated based on clinical evidence and response criteria. The response data will be 
summarized by each treatment (iRECIST will be used for response endpoints and disease 
measurements for iORR, iDCR, iDOR and iPFS; RECIST 1.1 guidelines will be used for 
response endpoints and disease measurements for ORR, DCR, DOR and PFS).  
ORR, DCR, DOR, PFS, and OS as well as iORR, iDCR, iDOR and iPFS will be 
calculated and summarized.  
• 
ORR or iORR is defined as the percentage of participants with a best overall 
confirmed CR or PR at any time as per disease-specific criteria.  
• 
DCR or iDCR is defined as the percentage of participants with a confirmed CR + PR 
at any time, plus SD 12 weeks. 
• 
DOR or iDOR is defined as the first documented evidence of CR or PR until disease 
progression or death due to any cause among participants who achieve an overall 
response (i.e., unconfirmed or confirmed CR or PR). Censoring rules will follow 
those of the PFS analysis. TTR is defined as the interval from the first dose of study 
treatment to the date of the first documented CR or PR. 
• 
PFS or iPFS defined as time from the date of randomization to the date of disease 
progression per clinical or radiological assessment or death due to any cause, 
whichever occurs earlier. For the analysis of PFS, if the participant received 
subsequent anticancer 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 participant does 
not have a documented date of event, PFS will be censored at the date of the last 
adequate assessment. 
At each interim analysis, if a participant does not have an event or is lost to follow-up, 
the participant will be censored at the last contact date (OS) or last imaging date (PFS). 
Further details on rules of censoring will be provided in the RAP. PFS and OS will be 
summarized using the Kaplan-Meier method. 
 


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10.5.3. 
Safety Analyses 
The Safety Population will be used for the analysis of safety data. All safety endpoints 
(e.g., adverse event data, clinical laboratory assessments, vital signs, etc.) will be 
summarized according to the scheduled, nominal visit at which they were collected and 
across all on-treatment time points. Complete details of the safety analyses will be 
provided in the RAP. 
10.5.3.1. 
Extent of Exposure 
The number of participants administered study treatment will be summarized according 
to the duration of therapy.  
10.5.3.2. 
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 NCI-CTCAE (version 5.0).  
Events will be summarized by frequency and proportion of total participants, by system 
organ class and preferred term. Separate summaries will be given for all AEs, treatment-
related AEs, SAEs, AESIs and AEs leading to dose modifications for toxicity 
management if irAEs of study treatment. AEs, if listed in the NCI-CTCAE (version 5.0) 
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.  
10.5.3.3. 
Clinical Laboratory Evaluations 
Hematology and clinical chemistry data will be summarized using frequencies and 
proportions according to NCI-CTCAE (version 5.0). Laboratory test results outside the 
reference ranges that do not have an associated NCI-CTCAE criteria will be summarized 
using proportions. Further details will be provided in the RAP.  
10.5.3.4. 
Other Safety Measures 
Data for vital signs will be summarized based on predetermined criteria identified to be 
of potential clinical concern. Further details will be provided in the RAP.  
10.5.4. 
Pharmacokinetic Analyses 
PK analysis will be the responsibility of the Clinical Pharmacology Modeling and 
Simulation (CPMS) Department, GSK. 
PK analysis of drug concentration-time data will be conducted by non-compartmental 
methods under the direction of CPMS. The following PK parameters may be determined 
as data permit:  
• 
maximum observed concentrations (Cmax) 


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• 
trough concentrations (Ctrough or Cmin) 
• 
Any additional PK parameters that may be calculated as data permit, e.g., area under 
the plasma or serum concentration-time curve (AUC(0-t)) will be presented in the 
study report  
Statistical analyses of the PK parameters data will be the responsibility of Clinical 
Statistics, GSK. 
Drug concentration-time data will be listed for each participant and summarized by 
descriptive statistics at each time point by cohort.   
The data from this study may be combined with the data from other studies for a 
population PK analysis. The details of such analysis will be outlined in a separate RAP; 
results of this analysis may be reported separately. 
10.5.5. 
Pharmacokinetic/Pharmacodynamic Analyses 
If deemed appropriate and if data permit, exploratory Pharmacokinetic / 
Pharmacodynamic analyses such as exposure-response relationships between exposure 
(e.g., dose, Cmax or Cmin) and safety/efficacy/PD parameters (e.g.: anti-tumor response, 
biomarkers) may be conducted. The details of such PK/PD analyses will be outlined in a 
separate RAP; results of these analyses may be included in a report separate from the 
clinical study report. The data from this study may be combined with the data from other 
studies, which may be reported separately. 
 
10.5.6. 
Tumor Kinetic Analyses 
Exploratory analyses may be performed to evaluate the effect of study treatment on the 
growth kinetics of individual tumor lesions. These analyses may include tumor lesion 
measurements from imaging scans performed earlier in the disease course (i.e., prior to 
screening scans). 
If deemed necessary, additional statistical analyses will be discussed in a separate RAP. 
The data from this study may be combined with the data from other studies, which may 
be reported separately. 
10.5.7. 
Other Analyses 
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11. 
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12. 
APPENDICES 
12.1. 
Appendix 1: Arms 
12.1.1. 
Standard of Care Arm 1: Docetaxel Alone (Part 2 ONLY) 
12.1.1.1. 
Protocol Amendment 4 Summary of Changes Specific to Docetaxel 
Arm  
Section # and Name 
Description of Change 
Brief Rationale 
Schedule of Activities 
Section 12.1.1.2 
Added physical exam for 
dosing visits. 
To align with the changes made 
to the other substudies Schedule 
of Activities. 
Schedule of Activities 
Section 12.1.1.2 
Removed details on number 
of slides for tissue sample 
to be sent by site. 
Decided this detail should be 
included in the SRM instead and 
was removed from protocol. 
Schedule of Activities 
Section 12.1.1.2 
Clarified that Docetaxel PK 
samples do not need to be 
collected after cycles have 
been completed. 
To provide clarity and address 
site questions. 
Schedule of Activities 
Section 12.1.1.2 
At the follow up visit, 
footnote added: If the 
participant dies before the 
first follow up, any 
subsequent anticancer 
therapy or radiotherapy 
should be recorded in the 
eCRF. 
To record any subsequent 
therapy the participant may have 
received after study 
discontinuation, if they die 
before first follow up is 
completed. 
Schedule of Activities 
Section 12.1.1.2 
Added footnote: 
Pre: predose sample to be 
collected prior to dosing per 
institutional guidance, as 
long as it is collected prior to 
dosing of the corresponding 
agent; EOI: End of infusion 
sample is in reference to EOI 
of the corresponding agent. 
To clarify the sample collection 
reference for predose and EOI. 
 


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Protocol Amendment 3 Summary of Changes Specific to Docetaxel Arm  
Section # and Name 
Description of Change 
Brief Rationale 
Schedule of Activities 
Section 12.1.1.2 
Added Schedule of 
Activities specific to 
docetaxel only treatment. 
To provide individual 
specific Schedule of 
Activities Table specific to 
standard of care arm in Part 
2. 
Study Treatment Section 
12.1.1.3 
Added required cycles for 
docetaxel. 
Provide additional 
guidance to align with 
standard practices for 
docetaxel administration. 
 


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12.1.1.2. 
Schedule of Activities Specific to Arm 1 Docetaxel (Part 2) 
The timing and number of planned study assessments, including [safety, pharmacokinetic, ADA, biomarker or others] assessments may be 
altered during the course of the study based on newly available data. 
 
Table 11 
Schedule of Activities – Screening: Standard of Care Arm 1: Docetaxel Alone 
Screening Study 
Assessments 
Screening1  
Notes 
Visit Window 
≤4 Weeks 
 
Informed Consent1 
X 
1. All screening assessments must be performed within 4 weeks (28 days) prior to first dose of study treatment unless otherwise 
specified. The informed consent may be signed within 45 days prior to first dose. 
 
Participant Registration2 
X 
2. Participants will be registered in RAMOS NG at screening. 
Inclusion/Exclusion Criteria 
X 
Review eligibility prior to randomization. 
Demographics, Medical History 
(including alcohol and tobacco 
use), Prior Medications, 
Disease History12 
X 
12. All known mutations should be entered in the eCRF as disease history. 
Prior Anticancer Treatment, 
Radiotherapy 
X 
 
Screening Safety 
AE/SAE/AESI Assessment3 
X 
3. After the initial AE/SAE report, the investigator is required to proactively follow each participant at subsequent visits/contacts. 
Refer to Section 9.4 for further details. 
ECOG PS 
X 
 
Physical Examination 
X 
 
Vital Signs, Height and Weight4 
X 
4. Vital signs include blood pressure, temperature, pulse, respiratory rate, and oxygen saturation. Height is recorded at Screening 
only. Record weight in kilograms. 
12-lead ECG 
X 
 
Echocardiogram or MUGA 
scan5 
X 
5. ECHO required at Screening within 28 days prior to first dose of study treatment, and during treatment phase if clinically 
indicated. MUGA scan may be used if ECHO not feasible.  
Screening Local Laboratory Assessments (Safety) 
Hepatitis B and C6 
X 
 


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Screening Study 
Assessments 
Screening1  
Notes 
Visit Window 
≤4 Weeks 
 
Serum β-hCG (for women of 
childbearing potential) 
≤3d 
Clinical Chemistry6, 
Coagulation6, Hematology6, 
Thyroid function6 
X 
6. Refer to Appendix 3 for a complete list of required assessments. Required within 7 days of randomization day. If Hepatitis B and 
C was performed within 3 months prior to first dose of SoC, repeat testing at screening is not required; otherwise, this testing is 
mandatory. 
Calculated CrCl7 
X 
7. CrCl is calculated by the CKD-EPI or Cockcroft-Gault formula. See Appendix 9. 
Troponin I or Troponin T 
X 
 
Urinalysis6 
X 
 
Screening Other Laboratory Assessments 
PD-L1 expression by IHC8 
X 
8. PD-L1 expression by IHC and type of assay utilized (i.e., Ventana SP263, Ventana SP142, Dako 28-8, or Dako 22C3) must be 
recorded in the eCRF, if known. Note: Test is not required to be performed by the site if not previously performed. 
Screening Disease Assessments 
 
Tumor Imaging9 
X 
9. Diagnostic quality CT scan of chest and abdomen with contrast must be obtained within 28 days of first dose. Baseline brain scan 
(MRI with and without IV gadolinium) should be obtained within 6 weeks of first dose if history of CNS disease or if clinically 
indicated. Bone scan should be obtained within 6 weeks of first dose if clinically indicated. See additional information regarding bone 
scans in Section 9.3.1. 
Pre-Baseline scans for Tumor 
Growth Kinetics10 
X 
10. Upon participant consent, up to 3 pre-baseline scans (within 12 months before the baseline scan) will be collected to assess 
tumor growth rate to support exploratory investigation of tumor growth kinetics (See Section 9.3.2 for details on images for 
submission). 
Screening Tumor Biopsies 
Fresh tumor tissue sample and 
Archival tumor11 
X 
11. Part 2: Tumor tissue at screening (either archival or fresh biopsy if archival tissue is unavailable), is required for all participants in 
Part 2: Fresh tumor tissue at screening is required in addition to an archival tissue for at least 20 participants in the SoC arm. 
Participants with inaccessible tumor or those participants that do not consent to the tumor biopsy procedure may be enrolled 
provided archival specimen is submitted. The archival specimen may have been obtained at any time from the time of initial 
diagnosis to time of study entry. Note: Enrollment may become limited during the study, as required, to ensure collection of fresh 
tissue samples as noted. 
 
Abbreviations: AE = adverse event; AESI = adverse events of special interest; β-hCG = β -human chorionic gonadotropin; CKD-EPI = chronic kidney disease epidemiology 
collaboration; CrCl = creatinine clearance; CT = computed tomography; ECG = electrocardiogram; ECHO = echocardiography; ECOG PS = Eastern Cooperative Oncology Group 
performance status; eCRF = electronic case report form; IHC = Immunohistochemistry; IWRS = interactive web response system; MRI = magnetic resonance imaging; MUGA = 
multi-gated acquisition; SAE = serious adverse event.  
 


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Table 12 
Schedule of Activities – Treatment Period: Standard of Care Arm 1: Docetaxel Alone 
On Treatment Study 
Assessments 
 
Notes 
Week 
1 
4 
7 
10 
13 
16 
19 
22 
25 
28 - 49 
52 - 106 
 
Day 
1 
22 
43 
64 
85 
106 
127 
148 
169 
190 - 337 
358 - 
736 
 
Visit Window 
±3-day window on treatment days unless otherwise noted (Visits occur once every 3 weeks during treatment period) 
Inclusion/Exclusion 
Criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Participant 
Randomization1 
X 
 
 
 
 
 
 
 
 
 
 
1. Once determined to be eligible, participants must be 
randomized via IWRS. Drug shipments will be managed via 
IWRS. Sites must allow up to 7 business days for shipment of 
study drug. Randomization can be done prior to Day 1, but no 
more than 3 days prior to Day 1. (Refer to SRM). 
Study treatments1 
Part 2 ONLY 
Docetaxel/SOC arm2 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
2. For those participants randomized to the SOC arm – docetaxel 
can be discontinued after 6 cycles as according to local 
prescribing information. Participants should receive premedication 
prior to receiving docetaxel as per local standards. 
On Treatment Safety  
AE/SAE/AESI 
Assessment3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
3. After the initial AE/SAE report, the investigator is required to 
proactively follow each participant at subsequent visits/contacts. 
All SAEs and non-serious AESIs will be followed until the event is 
resolved, stabilized, otherwise explained, or the participant is lost 
to follow-up. 
ECOG PS** 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Q6W* 
Q6W* 
*Q6W procedures are counted starting from Week 25 (i.e. the first 
Q6W visit is Week 31, then Week 37, etc.). 
Physical Examination** 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Q6W* 
Q6W* 
** Physical examinations and ECOG may be performed within 
one day of dosing (i.e., as opposed to the day of dosing), if 
necessary.  
Vital Signs and Weight4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
4. Vital signs include blood pressure, temperature, pulse, 
respiratory rate, and oxygen saturation. Weight is to be recorded 
at every other treatment visit in kilograms. Vital signs are to be 
performed predose on treatment days. 


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On Treatment Study 
Assessments 
 
Notes 
Week 
1 
4 
7 
10 
13 
16 
19 
22 
25 
28 - 49 
52 - 106 
 
Day 
1 
22 
43 
64 
85 
106 
127 
148 
169 
190 - 337 
358 - 
736 
 
Visit Window 
±3-day window on treatment days unless otherwise noted (Visits occur once every 3 weeks during treatment period) 
On Treatment Local Laboratory Assessments (Safety) – assessments may be performed up to 3 days prior to treatment 
Serum β-hCG (for women 
of childbearing potential)5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
5. Monthly urine pregnancy testing may also be performed as 
consistent with local standards however if a urine test is positive 
or borderline, or in the event of a missed menstrual period or 
suspicion of pregnancy, a serum β-hCG test will be required. 
Clinical Chemistry, 
Hematology, Coagulation6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
6. Refer to Appendix 3 for a complete list of required 
assessments. Laboratory testing may be performed one day prior 
to dosing if necessary. Not required to be tested on Day 1 if 
screening labs are within 72 hours from time of scheduled first 
dose.  
Thyroid function tests 
 
 
X 
 
X 
 
X 
 
X 
Q6W* 
Q6W* 
*Q6W procedures are counted starting from Week 25 (i.e. the first 
Q6W visit is Week 31, then Week 37, etc.). 
Calculated CrCl7 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
7. CrCl is calculated by the CKD-EPI or Cockcroft-Gault formula. 
Either formula is acceptable and must be consistently utilized for 
each participant throughout the study. See Appendix 9. 
Urinalysis 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 


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On Treatment Study 
Assessments 
 
Notes 
Week 
1 
4 
7 
10 
13 
16 
19 
22 
25 
28 - 49 
52 - 106 
 
Day 
1 
22 
43 
64 
85 
106 
127 
148 
169 
190 - 337 
358 - 
736 
 
Visit Window 
±3-day window on treatment days unless otherwise noted (Visits occur once every 3 weeks during treatment period) 
On Treatment Disease Assessments 
Tumor Imaging/Response 
Assessment8 
 
 
X 
 
X 
 
X 
 
X 
X8 
8. Diagnostic quality CT scan of chest and abdomen with contrast 
is required every 6 weeks (±1 week) until Week 49 and every 12 
weeks thereafter. Imaging/clinical assessments should be 
performed as indicated in Section 9.2. The same method of 
assessment is required throughout the study. Brain scan (MRI 
with and without IV gadolinium) and bone scan to be performed 
as clinically indicated during the treatment period. If a participant 
has achieved a PD, CR, or PR in the previous radiologic 
assessment, a repeat scan should be performed after at least 4 
weeks to confirm the response.  
On Treatment Patient-Reported Outcomes/Health-Related Quality of Life: completed in Part 2 ONLY 
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On Treatment Study 
Assessments 
 
Notes 
Week 
1 
4 
7 
10 
13 
16 
19 
22 
25 
28 - 49 
52 - 106 
 
Day 
1 
22 
43 
64 
85 
106 
127 
148 
169 
190 - 337 
358 - 
736 
 
Visit Window 
±3-day window on treatment days unless otherwise noted (Visits occur once every 3 weeks during treatment period) 
 
 
 
 
On Treatment Biomarkers 
On Treatment Tumor biopsies 
Fresh tumor tissue 
sample13 
 
 
X 
 
 
 
X13 
 
 
 
 
13. At least 20 participants in the SoC arm will have paired fresh 
tumor biopsies collected at Screening (prior to randomization) and 
Week 7 (±8 days). If tumor is amenable to biopsy and upon 
patient consent. 
Additional optional fresh tumor tissue sample will be collected at 
Week 19 at the time of imaging assessment and at the time of 
confirmed PR or PD (± 8 days), upon participant consent. Note: 
Enrollment may become limited during the study, as required, to 
ensure collection of fresh tissue samples as noted. 
On Treatment Pharmacokinetics  
Plasma SoC PK14 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
14. Draw sample  at: predose on Day 1 only; at end of SoC 
infusion (within 5 minutes) for all marked visits; and draw an 
additional sample between 2 and 5 hours after end of SoC 
infusion for all marked visits. There is a +5 minute window 
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On Treatment Study 
Assessments 
 
Notes 
Week 
1 
4 
7 
10 
13 
16 
19 
22 
25 
28 - 49 
52 - 106 
 
Day 
1 
22 
43 
64 
85 
106 
127 
148 
169 
190 - 337 
358 - 
736 
 
Visit Window 
±3-day window on treatment days unless otherwise noted (Visits occur once every 3 weeks during treatment period) 
allowance for the EOI time points. 
PK samples do not need to be collected after docetaxel cycles 
have been completed. 
On Treatment Pharmacogenetics 
Genetic research 15 
X 
 
 
 
 
 
 
 
 
 
 
15. Informed consent for optional genetic research must be 
obtained before collecting this sample. It is recommended that the 
optional research sample  be taken at the first opportunity after a 
participant has met all eligibility requirements before Day 1 or on 
Day 1. 
Abbreviations: ; AE = Adverse event; AESI = Adverse events of special interest; β-hCG = Beta-human chorionic gonadotropin; CKD-EPI = Chronic kidney disease epidemiology 
collaboration; CR = complete response; CrCl = Creatinine clearance; CT = computed tomography; CTCAE = Common Terminology Criteria for Adverse Events; ECOG PS = 
Eastern Cooperative Oncology Group performance status; EOI = End of infusion; 
 
; 
 
; IRR = infusion related reaction; 
; 
 
 PD = Progressive Disease; 
; PR = Partial response; Pre = Predose; 
 
 
 SAE = Serious adverse event. 
Pre: predose sample to be collected prior to dosing per institutional guidance, as long as it is collected prior to dosing of the corresponding agent; EOI: End of infusion sample is in 
reference to EOI of the corresponding agent. 
 
 
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Table 13 
Schedule of Activities – Treatment Discontinuation Visit (TDV) and Follow-Up: Standard of Care Arm 1: Docetaxel 
Alone 
TDV and Follow Up 
Assessments 
Treatment 
Discontinuation Visit1 
 
Survival 
Follow-Up1a 
Notes 
Visit Window 
+ 10 days 
 
 
Anticancer Treatment 
 
X* 
*If the participant dies before the first follow up, any subsequent anticancer therapy or radiotherapy should be 
recorded in the eCRF. 
 
*Follow up for survival will no longer be required once 85 events are reached for this arm. 
Concomitant 
Medications 
X 
 
 
TDV and Follow Up Safety 
AE/SAE/AESI 
Assessment2 
X 
 
2. After the initial AE/SAE report, the investigator is required to proactively follow each participant at subsequent 
visits/contacts. Refer to Section 9.4.1 and Section 9.4.3 for further details. 
ECOG PS 
X 
 
 
Physical Examination 
X 
 
 
Vital Signs and Weight3 
X 
 
3. Vital signs include blood pressure, temperature, pulse, respiratory rate, and oxygen saturation. 
TDV and Follow Up Local Laboratory Assessments 
Clinical Chemistry  
X 
 
 
Serum β-hCG (for 
women of childbearing 
potential) 
X 
 
 
Hematology 
X 
 
 
Thyroid function tests 
X 
 
 
Calculated CrCl 
X 
 
Urinalysis 
X 
 
TDV and Follow Up Disease Assessments 
Tumor 
Imaging/Response 
Assessment4 
X 
 
4. At the TDV, CT scan is required only if the last disease assessment did not show PD and was performed ≥6 
weeks before TDV. For participants who discontinue study treatment without documented disease progression, 
every effort should be made to continue monitoring disease status by tumor imaging using the same imaging 
schedule used while on treatment until the start of a new anticancer treatment, disease progression, pregnancy, 


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TDV and Follow Up 
Assessments 
Treatment 
Discontinuation Visit1 
 
Survival 
Follow-Up1a 
Notes 
Visit Window 
+ 10 days 
 
 
death, withdrawal of consent, or the end of the study, whichever occurs first. See additional information in 
Section 9.3.1  
Telephone call for 
survival status1a 
 
X 
 
TDV and Follow Up Tumor Biopsies 
Fresh tumor tissue 
sample 
X5 
 
5. If possible and upon participant consent, obtain an optional tumor tissue sample at time of confirmed PD or 
PR. 
TDV and Follow Up Patient-Reported Outcomes/Health-Related Quality of Life 
 
 
 
 
 
 
 
 
 
TDV and Follow Up Biomarkers 
Abbreviations: AE = Adverse event; AESI = Adverse events of special interest; β-hCG = Beta-human chorionic gonadotropin; CR = complete response; CrCl = Creatinine 
clearance; CT = computed tomography; CTCAE = Common Terminology Criteria for Adverse Events; ECOG PS = Eastern Cooperative Oncology Group performance status; 
eCRF = Electronic case report form; 
 
 
 
; 
; PD = Progressive Disease; 
 
; PR = Partial response; 
 
; SAE = Serious adverse event; TDV = Treatment Discontinuation Visit 
1. The assessments required at the study treatment discontinuation visit must be completed within 30 days from the date study treatment was discontinued and must occur prior to the 
start of subsequent anticancer therapy. If participant attends clinic for scheduled visit and decision is made to discontinue treatment, site can use this visit as the TDV and complete all 
assessments. 
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1a. Survival Follow-Up is the Observational Phase of the study. Participants will be followed for survival and subsequent anticancer therapy every 12 weeks after the last dose of study 
treatment, via telephone contact. Participants will be contacted every 12 weeks (±7 days) until death or participant’s withdrawal from further contact. Subsequent anticancer treatment 
and death date will be documented in the eCRF 
 


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12.1.1.3. 
Study Treatment 
Table 14 
Description and Administration of Docetaxel 
Name 
Docetaxel 
Description 
Microtubule stabilizer 
small molecule 
Dosage form/strength 
Refer to package insertb,c  
Dosage 
75 mg/m2 
Route of administration 
IV infusion 
Dosing instructionsa/frequency 
Administer diluted product/once Q3W 
a. 
Refer to the Study Reference Manual for detailed instructions on dosage and administration requirements. 
b. 
TAXOTERE PI, 2020; TAXOTERE SmPC, 2020. 
c. 
Docetaxel will be sourced locally from commercial stock, except in countries where regulatory authorities mandate 
that the Sponsor supply all study treatment(s) required for the conduct of a clinical trial. 
All participants randomly assigned to docetaxel-containing arms should be premedicated 
with oral corticosteroids (such as dexamethasone 16 mg per day or its equivalent) per 
local standards (e.g., 8 mg twice daily) for 3 days starting 1 day prior to docetaxel 
administration to reduce the incidence and severity of fluid retention as well as the 
severity of hypersensitivity reactions [TAXOTERE PI, 2020; TAXOTERE SmPC, 2020]. 
Intravenous corticosteroid premedication may also be utilized per local standard and at 
the discretion of the investigator.  
Docetaxel should be given for 6 cycles and may be discontinued after 6 cycles at the 
discretion of the investigator.  
The SRM will contain details on product handling, storage, preparation, and 
administration. Docetaxel will be administered according to the package insert and/or 
local standard. 
12.1.1.4. 
Dose Justification 
The dosage of docetaxel for this study, as a single agent and in combination, will be 
75mg/m2 Q3W, as described in the labels [TAXOTERE PI, 2020; TAXOTERE SmPC, 
2020] which is approved (a) as a single-agent for patients with locally advanced or 
metastatic NSCLC after platinum-based chemotherapy, and (b) in combination with 
cisplatin for unresectable, locally advanced or metastatic NSCLC for patients who have 
not received prior chemotherapy. 
12.1.1.5. 
Treatment of Overdose 
In the event of docetaxel overdose, refer to the instructions in the approved product label. 
Contact the Medical Monitor immediately and closely monitor the participant for AEs. 


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12.1.2. 
Substudy 1 (Arm 2): Feladilimab and Docetaxel Combination 
12.1.2.1. 
Protocol Amendment 5 Summary of Changes Specific to Feladilimab 
and Docetaxel Combination  
Section # and Name 
Description of Change 
Brief Rationale 
Schedule of Activities 
Section 12.1.2.2 
Added footnote to TDV 
SoA for survival follow up 
requirements 
To remove the survival 
follow up requirement for 
Substudy 1 when 85 events 
are reached as this will 
trigger final analysis   
 
Protocol Amendment 3 Summary of Changes Specific to Feladilimab and Docetaxel 
Combination  
Section # and Name 
Description of Change 
Brief Rationale 
Schedule of Activities 
Section 12.1.1.2 
Added Schedule of 
Activities specific to 
docetaxel only treatment. 
To provide individual 
specific Schedule of 
Activities Table specific to 
standard of care arm in Part 
2. 
Clinical Safety Summary 
Section 12.1.2.4.1, 
GSK3359609 PK/PD 
Summary Section 
12.1.2.5.1, GSK3359609 
Dose Rationale Section 
12.1.2.5.2 
Updated safety and PK/PD 
for GSK3359609. 
To align with 
GSK3359609 IB update 
version 5 and recent 
clinical data. 
 
 


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12.1.2.2. 
Schedule of Activities Specific to Feladilimab and Docetaxel Combination (Substudy 1) 
Table 15 
Schedule of Activities – Screening: Substudy 1 (Arm 2): Feladilimab and Docetaxel Combination 
Screening Study Assessment 
Screening1  
Notes 
Visit Window 
≤4 Weeks 
 
Informed Consent1 
X 
1. All screening assessments must be performed within 4 weeks (28 days) prior to first dose of study treatment unless otherwise 
specified. The informed consent may be signed within 45 days prior to first dose. 
 
Participant Registration2 
X 
2. Participants will be registered in RAMOS NG at screening. 
Inclusion/Exclusion Criteria12 
X 
12. All known mutations should be entered in the eCRF as disease history. 
Demographics, Medical History 
(including tobacco use), Prior 
Medications, Disease History 
X 
 
Anticancer Treatment 
X 
Screening Safety 
AE/SAE/AESI Assessment3 
X 
3. After the initial AE/SAE report, the investigator is required to proactively follow each participant at subsequent visits/contacts. All 
SAEs and non-serious AESIs will be followed until the event is resolved, stabilized, otherwise explained, or until the participant is 
lost to follow-up. 
ECOG PS 
X 
 
Physical Examination 
X 
 
Vital Signs, Height and Weight4 
X 
4. Vital signs include blood pressure, temperature, pulse, respiratory rate, and oxygen saturation. Height is recorded at Screening 
only. Record weight in kilograms. 
12-lead ECG 
X 
 
Echocardiogram or MUGA 
scan5 
X 
5. ECHO required at Screening within 28 days prior to first dose of study treatment, and during treatment phase if clinically 
indicated. MUGA scan may be used if ECHO not feasible.  
Screening Local Laboratory Assessments (Safety) 
Hepatitis B and C6 
X 
 
Serum β-hCG (for women of 
childbearing potential) 
≤3d 
Clinical Chemistry6, 
Coagulation6, Hematology6, 
Thyroid function6 
X 
6. Refer to Appendix 3 for a complete list of required assessments. Laboratory testing performed within 14 days of first dose of study 
intervention does not need to be repeated unless clinically indicated. If Hepatitis B and C testing was performed within 3 months 
prior to first dose of study intervention or SoC, repeat testing at screening is not required; otherwise, this testing is mandatory. 
Calculated CrCl7 
X 
7. CrCl is calculated by the CKD-EPI or Cockcroft-Gault formula. See Appendix 9. 
Troponin I or Troponin T 
X 
 
Urinalysis6 
X 
 


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Screening Study Assessment 
Screening1  
Notes 
Visit Window 
≤4 Weeks 
 
Screening Other Laboratory Assessments 
PD-L1 expression by IHC8 
X 
8. PD-L1 expression by IHC and type of assay utilized (i.e., Ventana SP263, Ventana SP142, Dako 28-8, or Dako 22C3) must be 
recorded in the eCRF, if known. Note: Test is not required to be performed by the site if not previously performed. 
Screening Disease Assessments 
Tumor Imaging9 
X 
9. Diagnostic quality CT scan of chest and abdomen with contrast must be obtained within 28 days of first dose. Baseline brain scan 
(MRI with or without IV gadolinium) should be obtained within 6 weeks of first dose if history of CNS disease or if clinically indicated. 
Bone scan should be obtained within 6 weeks of first dose if clinically indicated. See additional information regarding bone scans in 
Section 9.3.1. 
Pre-Baseline scans for Tumor 
Growth Kinetics10 
X 
10. Upon participant consent, up to 3 pre-baseline scans (within 6 months before the baseline scan) will be collected to assess 
tumor growth rate to support exploratory investigation of tumor growth kinetics (See Section 9.3.2 for details on images for 
submission). 
Screening Tumor Biopsies 
Fresh tumor tissue sample and 
Archival tumor11 
X 
11. Fresh tumor tissue sample AND an archival tissue sample obtained during screening is mandatory for at least 15 participants 
per study arm. 
Participants with inaccessible tumor or those participants that do not consent to the tumor biopsy procedure may be enrolled 
provided archival specimen is submitted. However, no participant will be allowed on study without either an archival specimen OR a 
fresh biopsy. The archival specimen may have been obtained at any time from the time of initial diagnosis to time of study entry. If 
only 10 unstained archival slides are available, participant may be considered eligible upon consultation/approval of the GSK 
Medical Monitor. Note: Enrollment may become limited during the study, as required, to ensure collection of fresh tissue samples as 
noted. 
 
Abbreviations: AE = adverse event; AESI = adverse events of special interest; β-hCG = β -human chorionic gonadotropin; CKD-EPI = chronic kidney disease epidemiology 
collaboration; CrCl = creatinine clearance; CT = computed tomography; ECG = electrocardiogram; ECHO = echocardiography; ECOG PS = Eastern Cooperative Oncology Group 
performance status; eCRF = electronic case report form; IHC = Immunohistochemistry; IWRS = interactive web response system; MRI = magnetic resonance imaging; MUGA = 
multi-gated acquisition; SAE = serious adverse event.  
 
 
 


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Table 16 
Schedule of Activities – Treatment Period: Substudy 1 (Arm 2): Feladilimab and Docetaxel Combination 
On Treatment Study 
Assessment 
 
Notes 
Week 
1 
4 
7 
10 
13 
16 
19 
22 
25 
28 - 49 
52 - 106 
 
Day 
1 
22 
43 
64 
85 
106 
127 
148 
169 
190 - 337 
358 - 
736 
 
Visit Window 
±3-day window on treatment days (Visits occur once every 3 weeks during treatment period) 
Inclusion/Exclusion 
Criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Participant 
Randomization1 
X 
 
 
 
 
 
 
 
 
 
 
1. Once determined to be eligible, participants must be 
randomized via IWRS. Drug shipments will be managed via 
IWRS. Sites must allow up to 7 business days for shipment of 
study drug. 
Study treatments1 
Administer Feladilimab 
(GSK3359609)* 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Q3W 
Q3W 
*Feladilimab (GSK3359609) must be administered first. 
Administration of Docetaxel must be started 1 hour and no more 
than 2 hours after the end of feladilimab (GSK3359609) infusion. 
Docetaxel2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Q3W2 
Q3W2 
2. Docetaxel will be administered according to the package insert 
and/or local standard. 
Chemotherapy premedication indicated on the day of dosing 
should be administered after feladilimab (GSK3359609) EOI. 
On Treatment Safety  
AE/SAE/AESI 
Assessment3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
3. After the initial AE/SAE report, the investigator is required to 
proactively follow each participant at subsequent visits/contacts. 
All SAEs and non-serious AESIs will be followed until the event is 
resolved, stabilized, otherwise explained, or the participant is lost 
to follow-up. 
ECOG PS 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Q6W* 
Q6W* 
*Q6W procedures are counted starting from Week 25 (i.e. the first 
Q6W visit is Week 31, then Week 37, etc.). 
Physical Examination** 
X 
 
 
X 
 
 
X 
X 
X 
Q6W* 
Q6W* 
** Physical examinations may be performed within one day of 
dosing (i.e., as opposed to the day of dosing), if necessary. 
Vital Signs and Weight4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
4. Vital signs include blood pressure, temperature, pulse, 
respiratory rate, and oxygen saturation. Weight is to be recorded 
at every other treatment visit in kilograms. Vital signs are to be 


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On Treatment Study 
Assessment 
 
Notes 
Week 
1 
4 
7 
10 
13 
16 
19 
22 
25 
28 - 49 
52 - 106 
 
Day 
1 
22 
43 
64 
85 
106 
127 
148 
169 
190 - 337 
358 - 
736 
 
Visit Window 
±3-day window on treatment days (Visits occur once every 3 weeks during treatment period) 
performed predose on treatment days. 
On Treatment Local Laboratory Assessments (Safety) – assessments may be performed up to 3 days prior to treatment 
Serum β-hCG (for women 
of childbearing potential)5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
5. Monthly urine pregnancy testing may also be performed as 
consistent with local standards however if a urine test is positive 
or borderline, or in the event of a missed menstrual period or 
suspicion of pregnancy, a serum β-hCG test will be required. 
Clinical Chemistry, 
Hematology6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
6. Refer to Appendix 3 for a complete list of required 
assessments. Laboratory testing performed within 14 days of first 
dose does not need to be repeated unless clinically indicated. 
Laboratory testing may be performed one day prior to dosing if 
necessary. 
Thyroid function tests 
 
 
X 
 
X 
 
X 
 
X 
Q6W* 
Q6W* 
*Q6W procedures are counted starting from Week 25 (i.e. the first 
Q6W visit is Week 31, then Week 37, etc.). 
Calculated CrCl7 
 
 
 
X 
 
 
X 
X 
X 
X 
X 
7. CrCl is calculated by the CKD-EPI or Cockcroft-Gault formula. 
Either formula is acceptable and must be consistently utilized for 
each participant throughout the study. See Appendix 9. 
Urinalysis 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
On Treatment Disease Assessments 
Tumor Imaging/Response 
Assessment8 
 
 
X 
 
X 
 
X 
 
X 
X8 
8. Diagnostic quality CT scan of chest and abdomen with contrast 
is required every 6 weeks (±1 week) until Week 49 and every 12 
weeks thereafter, until disease progression is confirmed by 
iRECIST. The same method of assessment is required throughout 
the study. Brain scan (MRI with or without IV gadolinium) and 
bone scan to be performed as clinically indicated during the 
treatment period. If a participant has achieved a PD, CR, or PR in 
the previous radiologic assessment, a repeat scan should be 
performed after at least 4 weeks to confirm the response. See 
additional information in Section 9.3.1. 
On Treatment Patient-Reported Outcomes/Health-Related Quality of Life 
 
 
 
 
 
 
 
 
 
 
 
 
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On Treatment Study 
Assessment 
 
Notes 
Week 
1 
4 
7 
10 
13 
16 
19 
22 
25 
28 - 49 
52 - 106 
 
Day 
1 
22 
43 
64 
85 
106 
127 
148 
169 
190 - 337 
358 - 
736 
 
Visit Window 
±3-day window on treatment days (Visits occur once every 3 weeks during treatment period) 
On Treatment Biomarkers 
On Treatment Tumor biopsies 
Fresh tumor tissue 
sample 
 
 
X 
 
 
 
X13 
 
 
 
 
13. At least 15 participants per treatment arm will have paired 
fresh tumor biopsies collected at Screening (prior to 
randomization) and Week 7 (± 8 days), if tumor is amenable to 
biopsy and upon participant consent.  
Additional optional fresh tumor tissue sample will be collected at 
Week 19 at the time of imaging assessment and at the time of 
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On Treatment Study 
Assessment 
 
Notes 
Week 
1 
4 
7 
10 
13 
16 
19 
22 
25 
28 - 49 
52 - 106 
 
Day 
1 
22 
43 
64 
85 
106 
127 
148 
169 
190 - 337 
358 - 
736 
 
Visit Window 
±3-day window on treatment days (Visits occur once every 3 weeks during treatment period) 
confirmed PR or PD (± 8 days), upon participant consent. Note: 
Enrollment may become limited during the study, as required, to 
ensure collection of fresh tissue samples as noted. 
On Treatment Pharmacokinetics and Anti-Drug Antibodies (ADA) 
Plasma SoC PK14 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
14. For Arm 1 and Arm 2: Draw sample (2 mL) at: predose on 
Day 1 only; at end of SoC infusion (within 5 minutes) for all 
marked visits; and draw an additional sample between 2 and 5 
hours after end of SoC infusion for all marked visits. There is a +5 
minute window allowance for the EOI time points. 
Plasma Feladilimab 
(GSK3359609; ICOS 
Agonist) PK15 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X15 
15. For Arm 2 only: Draw sample (2 mL) at predose for all marked 
visits. Additional samples also drawn at the following time points: 
Week 1 (Day 1) at end of infusion (EOI) (within 5 minutes) and 
EOI+4h. EOI samples also drawn at Week 13 and Week 25. After 
Week 25, draw samples every 12 weeks at predose only. There is 
a +5 minute window allowance for the EOI time points. 
Serum Feladilimab 
(GSK3359609; ICOS 
Agonist) ADA16 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X16 
16. For Arm 2 only: Draw sample (4 mL) at predose on ALL 
treatment visits; then starting with Week 25 predose samples to 
be collected every 12 weeks. Draw a sample at any time during 
visit for non-treatment visits. For participants with a positive ADA 
result at last regular visit an additional sample will be drawn at 6 
months after the last dose. 
Serum samples will be collected and tested for the presence of 
antibodies that bind to investigational agents as deemed 
appropriate. Feladilimab serum samples may also be tested for 
presence of antibodies that bind to Chinese Hamster Ovary 
(CHO) host cell proteins such as phospholipase B- like (PLBL2). 
Serum: IRR lab panel17 
 
 
 
 
 
 
 
 
 
 
 
17. Assessment ONLY required in participant experiencing 
anaphylaxis, serious hypersensitivity, or AEs related to study 
treatment administration that led to withdrawal from the study. 
Refer to Table 3 for list of analytes. Predose analysis will be 


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On Treatment Study 
Assessment 
 
Notes 
Week 
1 
4 
7 
10 
13 
16 
19 
22 
25 
28 - 49 
52 - 106 
 
Day 
1 
22 
43 
64 
85 
106 
127 
148 
169 
190 - 337 
358 - 
736 
 
Visit Window 
±3-day window on treatment days (Visits occur once every 3 weeks during treatment period) 
performed on the serum sample collected for feladilimab 
(GSK3359609) immunogenicity assessments. 
On Treatment Pharmacogenetics 
Genetic research18 
X 
 
 
 
 
 
 
 
 
 
 
18. Informed consent for optional genetic research must be 
obtained before collecting this sample. It is recommended that the 
optional research sample) be taken at the first opportunity after a 
participant has met all eligibility requirements before Day 1 or on 
Day 1. 
Abbreviations: ADA = Anti-drug antibody; AE = Adverse event; AESI = Adverse events of special interest; β-hCG = Beta-human chorionic gonadotropin; CKD-EPI = Chronic 
kidney disease epidemiology collaboration; CR = complete response; CrCl = Creatinine clearance; CT = computed tomography; CTCAE = Common Terminology Criteria for 
Adverse Events; ECOG PS = Eastern Cooperative Oncology Group performance status; EOI = End of infusion; 
 
; 
 
 IRR = infusion related reaction; 
 
; 
; PD = Progressive Disease; 
; PR = 
Partial response;
 
; SAE = Serious adverse event. 
 
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Table 17 
Schedule of Activities – Treatment Discontinuation Visit (TDV) and Follow-Up: Substudy 1 (Arm 2): Feladilimab 
and Docetaxel Combination 
TDV and Follow Up 
Assessments 
Treatment 
Discontinuation Visit1 
 
Survival 
Follow-Up1a 
Notes 
Visit Window 
+ 10 days 
 
 
Anticancer Treatment 
 
X* 
*Follow up for survival will no longer be required once 85 events are reached for this arm. 
Concomitant 
Medications 
X 
 
 
TDV and Follow Up Safety 
AE/SAE/AESI 
Assessment2 
X 
 
2. After the initial AE/SAE report, the investigator is required to proactively follow each participant at subsequent 
visits/contacts. All SAEs and non-serious AESI will be followed until the event is resolved, stabilized, otherwise 
explained, or the participant is lost to follow-up. 
ECOG PS 
X 
 
 
Physical Examination 
X 
 
 
Vital Signs and Weight3 
X 
 
3. Vital signs include blood pressure, temperature, pulse, respiratory rate, and oxygen saturation. 
TDV and Follow Up Local Laboratory Assessments 
Clinical Chemistry  
X 
 
 
Serum β-hCG (for 
women of childbearing 
potential) 
X 
 
 
Hematology 
X 
 
 
Thyroid function tests 
X 
 
 
Calculated CrCl 
X 
 
Urinalysis 
X 
 
TDV and Follow Up Disease Assessments 
Tumor 
Imaging/Response 
Assessment4 
X 
 
4. At the TDV, CT scan is required only if the last disease assessment did not show PD and was performed ≥6 
weeks before TDV. 
Telephone call for 
survival status1a 
 
X* 
*Follow up for survival will no longer be required once 85 events are reached for this arm. 
TDV and Follow Up Tumor Biopsies 
Fresh tumor tissue 
sample 
X5 
 
5. If possible, obtain an optional tumor tissue sample at time of confirmed PD or PR. 


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TDV and Follow Up 
Assessments 
Treatment 
Discontinuation Visit1 
 
Survival 
Follow-Up1a 
Notes 
Visit Window 
+ 10 days 
 
 
TDV and Follow Up Patient-Reported Outcomes/Health-Related Quality of Life 
 
 
 
 
 
 
 
 
 
 
 
TDV and Follow Up Biomarkers 
Abbreviations: AE = Adverse event; AESI = Adverse events of special interest; β-hCG = Beta-human chorionic gonadotropin; CR = complete response; CrCl = Creatinine 
clearance; CT = computed tomography; CTCAE = Common Terminology Criteria for Adverse Events; ECOG PS = Eastern Cooperative Oncology Group performance status; 
eCRF = Electronic case report form; 
 
 
 
; 
 PD = Progressive Disease; 
 
 PR = Partial response; 
 
; SAE = Serious adverse event; TDV = Treatment Discontinuation Visit 
 
1. The assessments required at the study treatment discontinuation visit must be completed within 30 days from the date study treatment was discontinued and must occur prior to the 
start of subsequent anticancer therapy. 
1a. Survival Follow-Up is the Observational Phase of the study. Participants will be followed for survival and subsequent anticancer therapy every 12 weeks after the last dose of study 
treatment, via telephone contact. Participants will be contacted every 12 weeks (±7 days) until death or participant’s withdrawal from further contact. Subsequent anticancer treatment 
will be documented in the eCRF. 
 
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12.1.2.3. 
Study Treatments 
Table 18 
Description and Administration of Arm 2 Study Treatments 
Name 
Docetaxel 
Feladilimab (GSK3359609; 
ICOS Agonist) 
Description 
Microtubule stabilizer 
small molecule 
Humanized anti-ICOS IgG4 
mAb 
Dosage form/strength 
Refer to package inserta 
Solution for injection/ 10 mg/mL  
Dosage 
75 mg/m2 
80 mg 
Route of administration 
IV infusion 
IV infusionb 
Dosing instructionsa/frequency 
Administer diluted product/once 
Q3W 
Administer diluted product/once 
Q3W 
a. 
TAXOTERE PI, 2020; TAXOTERE SmPC, 2020 
d. 
The study reference manual contains the details on product handling, storage, preparation, and administration. 
In feladilimab (ICOS Agonist)-containing arms, feladilimab will be administered first as 
a 30-minute IV infusion (infusion time may be adjusted based on infusion related 
reactions). The administration of the second agent in these arms must be started 1 hour 
and no more than 2 hours after the end of feladilimab infusion. Chemotherapy 
premedication indicated on the day of dosing should be administered after feladilimab 
EOI. Docetaxel will be administered according to the package insert and/or local 
standard. Participants should remain under observation at the study site post-study 
treatment infusion per the judgement of the investigator or as per institutional guidelines 
to monitor for potential infusion reactions or other adverse events.  
12.1.2.4. 
Rationale for ICOS Agonist/Docetaxel Combination 
Cancer immunity is described as a multistep process that elicits an effective antitumor 
response [Chen, 2013]. Each step can be negatively regulated, thus providing the tumor 
with redundant mechanisms by which to block an antitumor immune response. In some 
cases, tumors are highly dependent on a single mechanism, and in these cases, there is the 
potential to achieve significant clinical activity with a single agent immunomodulatory 
therapy. Robust antitumor responses including complete cure have been achieved in some 
cancers by modulating the patient’s immune system. Antibodies targeting the checkpoint 
receptors or their cognate ligands engaged in negative regulation of T cell responses, such 
as CTLA-4 and PD-1/PD-L1, have demonstrated efficacy as anticancer immunotherapies 
in a broad range of tumors including some solid tumors otherwise considered poorly 
immunogenic. 
However, a majority of tumors are non-responsive to this class of agents. One reason for 
the lack of response could be the existence of multiple mechanisms of immune 
suppression in the tumor microenvironment which prohibits effective antitumor immune 
responses. In these instances, combination therapies will likely be required. The clinical 
data generated by the combination of ipilimumab (anti-CTLA-4) and nivolumab (anti-
PD-1) in patients with metastatic melanoma is an example of the practice changing 
clinical benefit of such combinations [Wolchok, 2013]. 
In some patients, inhibition of negative immune checkpoint pathways alone may not 
elicit an effective antitumor response, and additional co-stimulatory signals may be 
necessary to mount an effective response. Immunomodulatory agents that target other 


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components of the cancer immunity cycle are needed to expand the population of patients 
and range of tumor types that may respond to immunotherapy as well as enhance the 
magnitude and duration of antitumor responses in patients whose tumors are already 
sensitive to current immunotherapy approaches. The ultimate aim is to improve the 
survival outcome in all disease settings including the advanced setting. 
Feladilimab is a humanized IgG4 anti-ICOS monoclonal antibody [Mayes, 2018] selected 
for its nanomolar (nM) binding to and agonist activity in ICOS-expressing CD4+ and 
CD8+ effector T cells. Feladilimab is specifically engineered as an Immunoglobulin 
(Ig)G4 hinge-stabilized isotype, IgG4PE, to markedly decrease binding affinity of the Fc 
(Fragment crystallizable) region of the mAb to activating Fcγ receptors and C1q, and 
thereby diminish the cytotoxic potential of feladilimab that would result in depletion of 
ICOS-positive T cells through antibody-dependent or complement-dependent cell 
mediated mechanisms, respectively. Moreover, the IgG4PE isotype retains functional 
binding to the Fc inhibitor receptor, FcRIIb, a feature described as critical for 
modulating antibody agonist activity [Li, 2011], which also may be essential for optimal 
ICOS agonist activity and its associated antitumor effects in humans. 
ICOS is a co-stimulatory receptor of the CD28/CTLA immunoglobulin super family with 
expression restricted to T cells [Horn, 2018]. ICOS is weakly expressed on resting TH17, 
follicular helper T and regulatory T (Treg) cells and yet is highly induced on CD4+ and 
CD8+ T cells upon T cell receptor (TCR) engagement and activation [Parmar, 1998, 
Paulos, 2010; Wakamatsu, 2013]. Upregulation of ICOS leads to both Th1 and Th2 
cytokine secretion and sustained effector T cell proliferation and function [Sharpe, 2002]. 
A growing body of evidence supports the concept that activating ICOS on CD4+ and 
CD8+ effector T cells has antitumor potential. 
The rationale for targeting ICOS in cancer has been established by multiple lines of 
nonclinical and clinical evidence. Engagement of the ICOS pathway with an ICOS-L-Fc 
fusion protein is shown to have potent antitumor activity in multiple syngeneic mouse 
tumor models [Ara, 2003]. Emerging data from patients treated with anti-CTLA-4 
antibodies suggest a positive role of ICOS+ effector T cells in mediating an antitumor 
immune response. Patients with metastatic melanoma [Di Giacomo, 2013], urothelial 
[Carthon, 2010], breast [Vonderheide, 2010] and prostate cancer [Chen, 2009] who have 
increased absolute counts of circulating and tumor infiltrating CD4+ICOS+ and 
CD8+ICOS+ T cells after ipilimumab treatment have significantly better treatment 
related outcomes than patients where little or no increases are observed. Importantly, it 
was shown that ipilimumab changes the ICOS+ T effector to Treg ratio, reversing an 
abundance of Tregs pre-treatment to a significant abundance of T effectors vs. Tregs 
following treatment [Liakou, 2008; Vonderheide, 2010]. As evidenced by the clinical 
data, ICOS+ T effector cells may be a positive predictive biomarker of ipilimumab 
response, and activation of this population of cells with an ICOS agonist antibody may 
confer an advantage by mounting a more robust immune antitumor response. 
Similar to the combination of platinum-containing chemotherapy with immuno-oncology 
agents (anti-PD-1) in metastatic non-squamous disease, i.e., the incorporation of the anti-
PD-1 inhibitor, pembrolizumab, to the pemetrexed/carboplatin backbone in the first-line 
metastatic non-squamous disease is an example for the IO agents to provide a higher 


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degree of benefit including a prolonged benefit combined with the immediate cytotoxic 
effects of the chemotherapy. The ICOS agonist/docetaxel combination has the potential 
to deliver a similar promise to later line NSCLC participants building on the existing 
docetaxel standard of care.  
Chemotherapy can promote tumor immunity by inducing immunogenic cell death as part 
of its intended therapeutic effect, as well as modulating distinct features of tumor 
immunobiology [Emens, 2015]. In preclinical models, combinations with various 
chemotherapy agents including docetaxel and platinum-based treatments with anti-PD-L1 
treatment showed increased efficacy associated with increased frequency of intratumoral 
subsets without antagonizing functional changes mediated by anti-PD-L1 [Cubas, 2016]. 
Combination of anti-ICOS surrogate antibody with carboplatin and paclitaxel showed 
some increase efficacy in the CT26 tumor model [Kilian, 2017a; Kilian, 2017b; Kilian, 
2017c; Kilian, 2017d]. 
12.1.2.4.1. Clinical Safety Summary 
As of the feladilimab Investigator Brochure data cutoff date of 16 March 2020, 249 
participants received at least 1 dose of monotherapy feladilimab in study 204691 at the 
following dose levels: 0.001 mg/kg (n=1), 0.003 mg/kg (n=1), 0.01 mg/kg (n=2), 0.03 
mg/kg (n=7), 0.10 mg/kg (n=25), 0.30 mg/kg (n=56), 1.0 mg/kg (n=126), 3.0 mg/kg 
(n=24), and 10 0 mg/kg (n=7). In these 249 participants, the most common AEs 
(occurring in 15% of participants overall regardless of dose level or relationship) were 
anemia (22%), asthenia (21%), nausea (19%), fatigue (18%), diarrhea (16%), and 
vomiting (15%).  
In study 204691, 10 participants received at least 1 dose of feladilimab 80 mg in 
combination with docetaxel 75 mg/m2 once every 3 weeks (safety cohort), 9 participants 
(90%) experienced at least 1 ≥Grade 3 AE, 2 of whom experienced Grade 5 events: 1 
participants had Grade 5 aspiration pneumonia and the other participant had Grade 5 
methicillin-resistant staphylococcus aureus (MRSA) chest infection and Grade 5 lower 
respiratory infection. Seven participants (70%) experienced at least 1 serious adverse 
event (SAE) of Grade 3; Grade 3: fatigue, dyspnea (1 event), hyponatremia, aspiration 
pneumonia, respiratory failure, hypotension, and diarrhea Grade 5: aspiration pneumonia, 
lower respiratory tract infection and staphylococcal infection. The Grade 5 events were 
reported in 2 participants (1 participant with aspiration pneumonia; 1 participant with 
lower respiratory tract infection and staphylococcal infection); the 3 events were not 
considered related to study treatment and the primary cause of death in both cases was 
sepsis.  
Refer to GSK3359609 IB [GSK Document Number 2017N319717_03] for further 
details.  
 


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12.1.2.5. 
Dose Justification (Substudy 1) 
12.1.2.5.1. Feladilimab Pharmacokinetics and Pharmacodynamics Summary 
The PK of feladilimab was evaluated after 30 minutes of IV infusion at doses from 0.001 
mg/kg to 10.0 mg/kg every 3 weeks (Q3W) in participants with solid tumors in Study 
204691. The plasma PK samples (received prior to the 2020 IB update cutoff date of 16 
March 2020) were analyzed with a validated bioanalytical method with a lower limit of 
quantitation (LLOQ) of 0.1 µg/mL. 
As of 16 March 2020, preliminary PK data in monotherapy cohorts were available in 1 
participant at 0.003 mg/kg, 2 participants at 0.01 mg/kg, 7 participants at 0.03 mg/kg, 25 
participants at 0.1 mg/kg, 52 participants at 0.3 mg/kg, 123 participants at 1.0 mg/kg, 23 
participants at 3.0 mg/kg, and 7 participants at 10.0 mg/kg dose. Preliminary PK data in 
pembrolizumab combination cohorts were available in 5 participants at 0.01 mg/kg, 
5 participants at 0.03 mg/kg, 13 participants at 0.1 mg/kg, 244 participants at 0.3 mg/kg, 
38 participants at 1.0 mg/kg, and 18 participants at 3.0 mg/kg dose. Preliminary PK data 
in GSK3174998 combination cohorts were available in 5 participants each at 8 and 24 mg 
and 1 participant at 80 mg fixed dose. Preliminary PK data in chemotherapy combination 
cohorts of the safety run-in were available in 55 participants at 80 mg fixed dose of 
feladilimab.  
Based on these preliminary data, the median plasma concentration-time profiles of 
feladilimab exhibit a bi-exponential decline. There are no changes in GSK3359609 PK 
when co-administered at doses from 0.01 to 3.0 mg/kg with biologic or chemotherapy 
partners. Furthermore, median feladilimab plasma PK profiles after dosing at 8, 24, and 
80 mg fixed doses were superimposable to the median PK profiles observed with 0.1, 0.3, 
and 1.0 mg/kg doses. Preliminary plasma PK parameters of feladilimab computed using 
noncompartmental analysis methods (AUC, C, and Cmax) calculated over the first dosing 
interval (up to 503 hours) exhibit approximate dose proportional increases in feladilimab 
exposure over the range of 0.01 to 10.0 mg/kg doses. Observed exposures (AUC and C) 
from body-weight based dose of 1.0 mg/kg (combined monotherapy and combination 
cohorts) and corresponding fixed dose equivalent of 80 mg (chemotherapy safety run-in) 
overlap with each other, indicating similar exposures can be achieved with a fixed dosing 
regimen. Preliminary population PK estimated geometric mean systemic half-life (t1/2) of 
feladilimab is approximately 19 days.  
Based on the preliminary data, median CD4 and CD8 receptor occupancy (RO) was 
maintained at or above 70% during the dosing interval of first cycle for doses 0.3 mg/kg 
as shown in Figure 7.  
Refer to GSK3359609 IB [GSK Document Number 2017N319717_03] for further 
details.  
 


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Figure 7 
Median CD4+ and CD8+ Receptor Occupancy (%RO) During the First 
Cycle of Feladilimab Administration as Monotherapy 
 
Feladilimab Dosing Frequency 
The systemic half-life of feladilimab is approximately 19 days based on the preliminary 
population PK analysis of data from ongoing study 204691. The existing feladilimab 


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Q3W regimen in the ongoing clinical study is also consistent with the Q3W dosing 
regimen typical with other IgG4 based monoclonal antibody therapies. The docetaxel 
label prescribes a Q3W regimen. Thus, feladilimab will be dosed Q3W in combination 
with docetaxel. Combination of feladilimab with any other treatment in other arms of this 
study may have a different dosing regimen as deemed appropriate.  
Rationale for Fixed Dose 
Therapeutic monoclonal antibodies are often dosed based on body-size due to the concept 
that this reduces inter-participant variability in drug exposure. However, body-weight 
dependency of PK parameters does not always explain all or even a majority of observed 
variability in the exposure of monoclonal antibodies [Zhao, 2017]. Hence, the selection 
of body-weight based versus fixed dosing in this study was evaluated through population 
PK modelling and simulation efforts.  
A preliminary population PK model (N = 637 participants; March 2020), which 
characterized the influence of body weight, age, and other participant covariates on 
exposure was developed. Results of this analysis indicate a feladilimab fixed dose is 
appropriate for trial participants across the bodyweight spectrum. Simulations show a 
feladilimab body weight-based dose results in slightly higher exposure in heavier weight 
participants and a feladilimab fixed dose results in slightly higher exposures in lighter 
participants. However, the range of exposures are similar between body-weight based and 
fixed dosing across the entire body weight spectrum and the exposures are maintained 
well within established clinical boundaries of safety at doses in the range of 24 to 80 mg 
Q3W (the highest studied dose in monotherapy deemed tolerable was 10 mg/kg or ~800 
mg). This suggests that there is no advantage of body-weight based dosing over fixed 
dosing and that lighter patients will not be more susceptible to treatment-related adverse 
events arising from marginal increases in exposure.  
Overall, these preliminary population PK simulations indicate that using fixed dosing 
would result in a similar range of exposures as that of body weight-based dosing. Also, 
fixed dosing offers the advantage of reduced dosing errors, reduced drug wastage, 
shortened preparation time, and improved ease of administration. Thus, a feladilimab 
fixed dose for Substudy 1 based on a reference body weight of 80 kg is reasonable and 
appropriate. 
Refer to GSK3359609 IB [GSK Document Number 2017N319717_03] for further 
details.  
12.1.2.5.2. Feladilimab Dose Rationale (Substudy 1) 
Based on the preliminary PK data described above in Section 12.1.2.5.1 and target 
engagement shown in Figure 7, median CD4 and CD8 receptor occupancy was 
maintained at or above 70% during the dosing interval of first cycle for doses ≥0.3 
mg/kg. Sufficiently high CD4+ RO is expected at peak exposures (89% to >99% RO) as 
well as at trough exposures (69% to >99% RO) at steady-state with the proposed 80 mg 
dose in substudy 1. 


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Collectively, based on the safety and exposure data from the Phase 1 study and the 
predicted target engagement, the 80-mg dose will be evaluated in combination with 
docetaxel in this study. No drug-drug interaction related changes are expected in 
feladilimab PK with docetaxel co-administration. The currently planned 80 mg 
feladilimab dose may be adjusted lower to 24 mg or increased to 240 mg based on any 
emerging safety, exposure and/or pharmacodynamic data. 
12.1.2.5.3. Docetaxel Dose Rationale 
Docetaxel is a semisynthetic taxane approved in different tumor indications. The dosage 
of docetaxel as a single agent and in combination for several tumor indications, including 
NSCLC and HNSCC, is 75 mg/m2, every three weeks; thus, this dose and schedule was 
selected in combination with feladilimab. There are no drug-drug interaction related 
changes expected in docetaxel PK on co-administration with feladilimab. 
12.1.2.6. 
Treatment of Overdose 
An overdose is defined as administration of a dose that is at least 50% greater than the 
intended dose. In the event of an overdose, the investigator must: 
1. Contact the Medical Monitor immediately. 
2. Closely monitor the participant for adverse events and laboratory abnormalities 
for at least 130 days. 
3. Obtain a plasma sample for PK analysis within 28 days from the date of the last 
dose of study treatment if requested by the Medical Monitor (determined on a 
case-by-case basis).  
4. Document the quantity of the excess dose as well as the duration of the 
overdosing in the eCRF.  
Decisions regarding dose interruptions or modifications will be made by the investigator 
in consultation with the Medical Monitor based on the clinical evaluation of the 
participant.  
There is no specific antidote for overdose with the experimental treatments being 
evaluated in this study. In the event of a suspected overdose, it is recommended that the 
appropriate supportive clinical care be instituted as dictated by the participant’s clinical 
status.  
 


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12.1.3. 
Arm 3: Feladilimab and Ipilimumab Combination 
12.1.3.1. 
Protocol Amendment 5 Summary of Changes Specific to Feladilimab 
and Ipilimumab Arm  
Section # and Name 
Description of Change 
Brief Rationale 
Schedule of Activities 
Section 12.1.3.2 
Added footnote to SoAs (on-
treatment and TDV) for 
biomarker, PK, and ADA 
samples SoA  
To align with decision to no 
longer collect samples from 
participants in this arm  
Schedule of Activities 
Section 12.1.3.2 
Added footnote to TDV SoA 
for survival follow up 
requirements 
To remove the survival follow 
up requirement for this arm   
Dose Modification and 
Management 
Guidelines Section 
12.1.3.10 
Moved dose modification 
guidelines to this section 
from the master protocol  
To include the dose 
modification guidelines 
specific to the regimen in this 
arm  
Safety Evaluation 
Section 12.1.3.11 
Moved Part 1 Analysis text 
from master protocol  
To avoid duplication and better 
clarify the analysis for this arm 
Risk-benefit Section 
12.1.3.14 
Moved risk management and 
mitigation strategy to this 
section from the master 
protocol  
To include risk management 
and mitigation strategy specific 
to the regimen in this arm  
 
Protocol Amendment 4 Summary of Changes Specific to Feladilimab and 
Ipilimumab Arm  
Section # and Name 
Description of Change 
Brief Rationale 
Schedule of Activities 
Section 12.1.3.2 
Added physical exam for 
dosing visits. 
As this is a new combination 
being tested, decision was 
made to require a physical 
exam at every dosing visit. 
Schedule of Activities 
Section 12.1.3.2 
Time window for plasma 
feladilimab end of infusion 
PK was extended from 5 min 
to 15 min 
To allow the site a longer time 
window to collect the end of 
infusion PK sample 
Schedule of Activities 
Section 12.1.3.2 
Removed details on number 
of slides for tissue sample to 
Decided this detail should be 
included in the SRM instead 
and was removed from 


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be sent by site. 
protocol. 
Schedule of Activities 
Section 12.1.3.2 
Added creatinine clearance to 
screening assessments 
To correct the omission of 
creatinine clearance. 
Schedule of Activities 
Section 12.1.3.2 
At the follow up visit, 
footnote added: If the 
participant dies before the 
first follow up, any 
subsequent anticancer 
therapy or radiotherapy 
should be recorded in the 
eCRF. 
To record any subsequent 
therapy the participant may 
have received after study 
discontinuation, if they die 
before first follow up is 
completed. 
Futility Evaluation 
Section 12.1.3.12 
Clarify ipilimumab cohort 
will start at 3mg/kg dose. 
To align with study strategy. 
Schedule of Activities 
Section 12.1.3.2 
Added footnote: 
Pre: predose sample to be 
collected prior to dosing per 
institutional guidance, as 
long as it is collected prior to 
dosing of the corresponding 
agent; EOI: End of infusion 
sample is in reference to EOI 
of the corresponding agent. 
To clarify the sample 
collection reference for predose 
and EOI. 
Schedule of Activities 
Section 12.1.3.2 
Added in the TDV SOA:  
In the event of 
hypersensitivity reaction that 
is clinically significant and/or 
leads to study treatment 
discontinuation, an additional 
sample should be collected at 
24 weeks post last dose of 
study treatment. 
To correct the omission of 
hypersensitivity collection of 
ADA samples at TDV and 
added sample collection for 
feladilimab. 


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12.1.3.2. 
Schedule of Activities Specific to Ipilimumab and Feladilimab Combination  
The timing and number of planned study assessments (including safety, pharmacokinetic, ADA, biomarker or other assessments) may 
be altered during the course of the study based on newly available data. 
Table 19 
Schedule of Activities – Screening: Arm 3: Ipilimumab and Feladilimab Combination 
Screening Study 
Assessments 
Screening1  
Notes 
Visit Window ≤4 Wk 
 
 
Informed Consent1 
X 
1. All screening assessments must be performed within 4 weeks (28 days) prior to first dose of study treatment unless otherwise 
specified. The informed consent may be signed within 45 days prior to first dose. 
Participant Registration2 
X 
2. Participants will be registered in RAMOS NG at screening. 
Inclusion/Exclusion Criteria 
X 
Review eligibility prior to randomization. 
Demographics, Medical History 
(incl. alcohol & tobacco use), 
Prior Medications, Disease 
History12 
X 
12. All known mutations should be entered in the eCRF as disease history. 
Prior Anticancer Treatment, 
Radiotherapy 
X 
 
Screening Safety 
AE/SAE/AESI Assessment3 
X 
3. After the initial AE/SAE report, the investigator is required to proactively follow each participant at subsequent visits/contacts. 
Refer to Section 9.4 for further details. 
ECOG PS 
X 
 
Physical Examination 
X 
 
Vital Signs, Height and Weight4 
X 
4. Vital signs include blood pressure, temperature, pulse, respiratory rate, and oxygen saturation. Height is recorded at Screening 
only. Record weight in kilograms. 
12-lead ECG 
X 
 
Echocardiogram or MUGA scan5 
X 
5. ECHO required at Screening within 28 days prior to first dose of study treatment, and during treatment phase if clinically 
indicated. MUGA scan may be used if ECHO not feasible.  


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Screening Study 
Assessments 
Screening1  
Notes 
Visit Window ≤4 Wk 
 
 
Screening Local Laboratory Assessments (Safety) 
Hepatitis B and C6 
X 
 
Serum β-hCG (for women of 
childbearing potential) 
≤3d 
Clinical Chemistry6, 
Coagulation6, Hematology6, 
Thyroid function6 
X 
6. Refer to Appendix 3 for a complete list of required assessments. Required within 7 days of randomization day. Not required to be 
tested on Day 1 if screening labs are within 72 hours from time of scheduled first dose. Must be drawn predose or up to 3 days prior 
to dosing. If Hepatitis B and C was performed within 3 months prior to first dose of study intervention or SoC, repeat testing at 
screening is not required; otherwise, this testing is mandatory. 
Calculated CrCl7 
X 
7. CrCl is calculated by the CKD-EPI or Cockcroft-Gault formula. See Appendix 9. 
Troponin I or Troponin T 
X 
 
Urinalysis6 
X 
 
Screening Other Laboratory Assessments 
PD-L1 expression by IHC7 
X 
7. PD-L1 expression by IHC and type of assay utilized (i.e., Ventana SP263, Ventana SP142, Dako 28-8, or Dako 22C3) must be 
recorded in the eCRF, if known. Note: Test is not required to be performed by the site if not previously performed. 
Screening Disease Assessments 
 
Tumor Imaging8 
X 
8. Diagnostic quality CT scan of chest and abdomen with contrast must be obtained within 28 days of first dose. Baseline brain scan 
(MRI with and without IV gadolinium) should be obtained within 6 weeks of first dose if history of CNS disease or if clinically 
indicated. Bone scan should be obtained within 6 weeks of first dose if clinically indicated. See additional information regarding bone 
scans in Section 9.3.1. 
Pre-Baseline scans for Tumor 
Growth Kinetics9 
X 
9. Upon participant consent, up to 3 pre-baseline scans (within 12 months before the baseline scan) will be collected to assess 
tumor growth rate to support exploratory investigation of tumor growth kinetics (See Section 9.3.2 for details on images for 
submission). 


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Screening Study 
Assessments 
Screening1  
Notes 
Visit Window ≤4 Wk 
 
 
Screening Tumor Biopsies 
Fresh tumor tissue sample and 
Archival tumor10 
X 
10. Part 1: All participants are required to have tumor tissue available (archival or fresh biopsy) prior to start of study treatment. A 
fresh biopsy is required if archival tissue is unavailable. Following Part 1 initial safety evaluation (up to first 10 participants), for the 
additional participants enrolled to assess further safety as well as PK/PD, fresh tumor tissue AND archival tumor tissue samples at 
screening are required prior to start of study treatment. 
Part 2: Tumor tissue at screening (either archival or fresh biopsy if archival tissue is unavailable), is required for all participants in 
Part 2. Fresh tumor tissue at screening is required in addition to an archival tissue for at least 20 participants for this arm. 
Participants with inaccessible tumor or those participants that do not consent to the tumor biopsy procedure may be enrolled 
provided an archival specimen is submitted. The archival specimen may have been obtained at any time from the time of initial 
diagnosis to time of study entry. Note: Enrollment may become limited during the study, as required, to ensure collection of fresh 
tissue samples as noted. 
‘Abbreviations: AE = adverse event; AESI = adverse events of special interest; β-hCG = β -human chorionic gonadotropin; CKD-EPI = chronic kidney disease epidemiology 
collaboration; CrCl = creatinine clearance; CT = computed tomography; ECG = electrocardiogram; ECHO = echocardiography; ECOG PS = Eastern Cooperative Oncology Group 
performance status; eCRF = electronic case report form; IHC = Immunohistochemistry; IWRS = interactive web response system; MRI = magnetic resonance imaging; MUGA = 
multi-gated acquisition; SAE = serious adverse event. 
 


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Table 20 
Schedule of Activities – Treatment Period: Arm 3: Ipilimumab and Feladilimab Combination 
On Treatment Study 
Assessments 
 
Notes 
Week 
1 
4 
7 
10 
13 
16 
19 
22 
25 
28 - 
49 
52 - 106 
 
Day 
1 
22 
43 
64 
85 
106 
127 
148 
169 
190 - 
337 
358 - 
736 
 
Visit Window 
±3-day window on treatment days unless otherwise noted. (Visits occur once every 3 weeks during treatment period) 
Inclusion/Exclusion Criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Participant Randomization1 
X 
 
 
 
 
 
 
 
 
 
 
1. Once determined to be eligible, participants must be 
randomized via IWRS. Drug shipments will be managed via 
IWRS. Sites must allow up to 7 business days for shipment 
of study drug. Randomization can be done prior to Day 1, but 
no more than 3 days prior to Day 1. (Refer to SRM). 
Study treatments1 
Administer Feladilimab 
(GSK3359609)* 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Q3W 
*Feladilimab (GSK3359609) must be administered within ±3 
days of scheduled visit unless otherwise indicated. Refer to 
Section 5.2 for maximum duration of study treatment. 
feladilimab (GSK3359609) will be administered first and 
ipilimumab will be administered at least 30 minutes and no 
longer than one hour following feladilimab (GSK3359609) 
EOI. 
Administer Ipilimumab2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Q3W 
2. Feladilimab (GSK3359609) will be administered first and 
ipilimumab will be administered at least 30 minutes and no 
longer than one hour following feladilimab (GSK3359609) 
EOI. Refer to Section 5.2 for maximum duration of study 
treatment. 
Dosing interval can be extended to Q6W for toxicity or 
intolerance 
On Treatment Safety  
AE/SAE/AESI Assessment3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
3. After the initial AE/SAE report, the investigator is required 
to proactively follow each participant at subsequent 
visits/contacts. All SAEs and non-serious AESIs will be 
followed until the event is resolved, stabilized, otherwise 


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On Treatment Study 
Assessments 
 
Notes 
Week 
1 
4 
7 
10 
13 
16 
19 
22 
25 
28 - 
49 
52 - 106 
 
Day 
1 
22 
43 
64 
85 
106 
127 
148 
169 
190 - 
337 
358 - 
736 
 
Visit Window 
±3-day window on treatment days unless otherwise noted. (Visits occur once every 3 weeks during treatment period) 
explained, or the participant is lost to follow-up. 
ECOG PS** 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Q6W* 
Q6W* 
*Q6W procedures are counted starting from Week 25 (i.e. 
the first Q6W visit is Week 31, then Week 37, etc.), unless 
more frequent assessments are clinically indicated. 
Physical Examination** 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Q6W* 
Q6W* 
** Physical examinations and ECOG may be performed 
within 24 hours prior to dosing (i.e., as opposed to the day of 
dosing), if necessary. 
Vital Signs and Weight4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
4. Vital signs include blood pressure, temperature, pulse, 
respiratory rate, and oxygen saturation. Weight is to be 
recorded at every other treatment visit in kilograms. Vital 
signs are to be performed predose on treatment days. 
On Treatment Local Laboratory Assessments (Safety) – assessments may be performed up to 3 days prior to treatment 
Serum β-hCG (for women of 
childbearing potential)5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
5. Monthly urine pregnancy testing may also be performed 
as consistent with local standards however if a urine test is 
positive or borderline, or in the event of a missed menstrual 
period or suspicion of pregnancy, a serum β-hCG test will be 
required. 
Clinical Chemistry, 
Hematology6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
6. Refer to Appendix 3 for a complete list of required 
assessments. Laboratory testing may be performed one day 
prior to dosing if necessary. Not required to be tested on Day 
1 if screening labs are within 72 hours from time of 
scheduled first dose.  
Thyroid function tests 
 
 
X 
 
X 
 
X 
 
X 
Q6W* 
Q6W* 
*Q6W procedures are counted starting from Week 25 (i.e. 
the first Q6W visit is Week 31, then Week 37, etc.). 
Calculated CrCl7 
 
 
 
X 
 
 
X 
X 
X 
X 
X 
7. CrCl is calculated by the CKD-EPI or Cockcroft-Gault 
formula. Either formula is acceptable and must be 
consistently utilized for each participant throughout the 
study. See Appendix 9. 


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On Treatment Study 
Assessments 
 
Notes 
Week 
1 
4 
7 
10 
13 
16 
19 
22 
25 
28 - 
49 
52 - 106 
 
Day 
1 
22 
43 
64 
85 
106 
127 
148 
169 
190 - 
337 
358 - 
736 
 
Visit Window 
±3-day window on treatment days unless otherwise noted. (Visits occur once every 3 weeks during treatment period) 
Urinalysis 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
On Treatment Disease Assessments 
Tumor Imaging/Response 
Assessment8 
 
 
X 
 
X 
 
X 
 
X 
X8 
8. Diagnostic quality CT scan of chest and abdomen with 
contrast is required every 6 weeks (±1 week) until Week 49 
and every 12 weeks thereafter. Imaging/clinical assessments 
should be performed as indicated in Section 9.2. The same 
method of assessment is required throughout the study. 
Brain scan (MRI with and without IV gadolinium) and bone 
scan to be performed as clinically indicated during the 
treatment period. If a participant has achieved a PD, CR, or 
PR in the previous radiologic assessment, a repeat scan 
should be performed after at least 4 weeks to confirm the 
response.  
On Treatment Patient-Reported Outcomes/Health-Related Quality of Life: Part 2 ONLY  
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On Treatment Study 
Assessments 
 
Notes 
Week 
1 
4 
7 
10 
13 
16 
19 
22 
25 
28 - 
49 
52 - 106 
 
Day 
1 
22 
43 
64 
85 
106 
127 
148 
169 
190 - 
337 
358 - 
736 
 
Visit Window 
±3-day window on treatment days unless otherwise noted. (Visits occur once every 3 weeks during treatment period) 
On Treatment Biomarkers21 
On Treatment Tumor biopsies22 
Fresh tumor tissue sample13 
 
 
X 
 
 
 
X13 
 
 
 
 
13.Part 1: For participants in the safety evaluation for each 
substudy, fresh biopsies at week 7 (± 8 days) is optional. 
Following Part 1 initial safety evaluation (up to 10 
participants), the additional participants enrolled to assess 
further safety as well as PK/PD are required to provide a 
fresh biopsy obtained at week 7 (± 8 days).  
22. On treatment biopsy for participants in the PK/PD cohort 
is no longer required for ongoing participants in this arm. 
Part 2: Fresh biopsy collected at week 7 (± 8 days) is 
optional for participants in Part 2, if tumor is amenable to 
biopsy and upon participant consent. However, fresh biopsy 
at week 7 (± 8 days) is required for at least 20 participants 
for this arm who also provided a fresh biopsy at screening. 
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On Treatment Study 
Assessments 
 
Notes 
Week 
1 
4 
7 
10 
13 
16 
19 
22 
25 
28 - 
49 
52 - 106 
 
Day 
1 
22 
43 
64 
85 
106 
127 
148 
169 
190 - 
337 
358 - 
736 
 
Visit Window 
±3-day window on treatment days unless otherwise noted. (Visits occur once every 3 weeks during treatment period) 
Additional optional fresh tumor tissue sample will be 
collected at Week 19 at the time of imaging assessment and 
at the time of confirmed PR or PD (± 8 days), upon 
participant consent. Note: Enrollment may become limited 
during the study, as required, to ensure collection of fresh 
tissue samples as noted. 
On Treatment Pharmacokinetics and Anti-Drug Antibodies (ADA) 
Plasma Feladilimab 
(GSK3359609; ICOS 
Agonist) PK14, 23 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X14 
14. Draw sample (2 mL) at predose for all marked visits. 
Additional samples also drawn at the following time points: 
Week 1 (Day 1) at end of infusion (EOI) (within 15 minutes) 
and EOI+4h. EOI samples also drawn at Week 13 and Week 
25. After Week 25, draw samples every 12 weeks at predose 
only. There is a +15 minutes window allowance for the EOI 
time points. 
23. Collection of on treatment ICOS PK is no longer required 
for ongoing participants in this arm. 
Ipilimumab PK24 
Pre, 
EOI* 
Pre, 
EOI 
Pre, 
EOI 
Pre, 
EOI 
Pre, 
EOI 
Pre, 
EOI 
Pre, 
EOI15 
 
 
Pre15 
Pre15 
*Part 1 ONLY: Additional collection time points for PKs on 
day 8 (± 2 days) and day 15 (± 3 days). 
15. To be collected predose, EOI every 3 weeks until Week 
19, then predose only every 18 weeks thereafter. If 
ipilimumab is given on a differing scheduling frequency, pre 
and EOI should be collected relative to dosing on infusion 
days only. 
24. Collection of on treatment ipilimumab PK is no longer 
required for ongoing participants in this arm. 
Serum Feladilimab 
(GSK3359609; ICOS 
Agonist) ADA16, 25 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X16 
16. Draw sample (4 mL) at predose on ALL treatment visits; 
then starting with Week 25 predose samples to be collected 
every 12 weeks. Draw a sample at any time during visit for 
non-treatment visits. Serum samples will be collected and 
tested for the presence of antibodies that bind to 


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On Treatment Study 
Assessments 
 
Notes 
Week 
1 
4 
7 
10 
13 
16 
19 
22 
25 
28 - 
49 
52 - 106 
 
Day 
1 
22 
43 
64 
85 
106 
127 
148 
169 
190 - 
337 
358 - 
736 
 
Visit Window 
±3-day window on treatment days unless otherwise noted. (Visits occur once every 3 weeks during treatment period) 
investigational agents as deemed appropriate. Feladilimab 
serum samples may also be tested for presence of 
antibodies that bind to Chinese Hamster Ovary (CHO) host 
cell proteins such as phospholipase B- like (PLBL2). 
25. Collection of on treatment ICOS ADA is no longer 
required for ongoing participants in this arm. 
  
Serum Ipilimumab ADA17, 26 
Pre 
Pre 
Pre 
Pre 
Pre 
Pre 
Pre18 
 
 
Pre18 
Pre18 
17. Serum samples are required to be collected prior to 
dosing (i.e., predose) on each dosing day and at the 
indicated assessment visits following study treatment 
discontinuation, and one sample collected 12 weeks post 
last dose of study treatment. In the event of hypersensitivity 
reaction that is clinically significant and/or leads to study 
treatment discontinuation, serum samples should be 
collected 30 days, 12 weeks, and 24 weeks post last dose of 
study treatment. 
18. To be collected every 3 weeks until Week 19, then every 
18 weeks thereafter. 
26. Collection of on treatment ipilimumab ADA is no longer 
required for ongoing participants in this arm. 
Serum: IRR lab panel19 
 
 
 
 
 
 
 
 
 
 
 
19. Assessment ONLY required in participant experiencing 
anaphylaxis, serious hypersensitivity, or AEs related to study 
treatment administration that led to withdrawal from the 
study. Refer to Table 3 for list of analytes. Predose analysis 
will be performed on the serum sample collected for 
feladilimab (GSK3359609) and/or ipilimumab 
immunogenicity assessments. 
On Treatment Pharmacogenetics 
Genetic research20 
X 
 
 
 
 
 
 
 
 
 
 
20. Informed consent for optional genetic research must be 


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On Treatment Study 
Assessments 
 
Notes 
Week 
1 
4 
7 
10 
13 
16 
19 
22 
25 
28 - 
49 
52 - 106 
 
Day 
1 
22 
43 
64 
85 
106 
127 
148 
169 
190 - 
337 
358 - 
736 
 
Visit Window 
±3-day window on treatment days unless otherwise noted. (Visits occur once every 3 weeks during treatment period) 
obtained before collecting this sample. It is recommended 
that the optional research sample be taken at the first 
opportunity after a participant has met all eligibility 
requirements before Day 1 or on Day 1. 
Abbreviations: ADA = Anti-drug antibody; AE = Adverse event; AESI = Adverse events of special interest; β-hCG = Beta-human chorionic gonadotropin; CKD-EPI = Chronic 
kidney disease epidemiology collaboration; CR = complete response; CrCl = Creatinine clearance; CT = computed tomography; CTCAE = Common Terminology Criteria for 
Adverse Events; ECOG PS = Eastern Cooperative Oncology Group performance status; EOI = End of infusion; 
 
; 
 
 ICOS = inducible T Cell co-stimulator; IRR = infusion related reaction;
 
 
; PD = Progressive Disease; 
; PR = 
Partial response; Pre = Predose; 
 
; SAE = Serious adverse event. 
Pre: predose sample to be collected prior to dosing per institutional guidance, as long as it is collected prior to dosing of the corresponding agent; EOI: End of infusion sample is in 
reference to EOI of the corresponding agent. 
 
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Table 21 
Schedule of Activities – Treatment Discontinuation Visit and Follow-Up: Arm 3: Ipilimumab and Feladilimab 
Combination 
TDV and Follow Up 
Assessments 
Treatment 
Discontinuation Visit 
 
Survival 
Follow-Up 
Notes 
Visit Window 
+ 10 days 
 
 
Anticancer Treatment 
 
X* 
* Follow up for survival is no longer required for participants in this arm. 
 
  
  
Concomitant 
Medications 
X 
 
 
TDV and Follow Up Safety 
AE/SAE/AESI 
Assessment2 
X 
 
2. After the initial AE/SAE report, the investigator is required to proactively follow each participant at subsequent 
visits/contacts. Refer to Section 9.4.1 and Section 9.4.3 for further details.. 
ECOG PS 
X 
 
 
Physical Examination 
X 
 
 
Vital Signs and Weight3 
X 
 
3. Vital signs include blood pressure, temperature, pulse, respiratory rate, and oxygen saturation. 
TDV and Follow Up Local Laboratory Assessments 
Clinical Chemistry  
X 
 
 
Serum β-hCG (for 
women of childbearing 
potential) 
X 
 
 
Hematology 
X 
 
 
Thyroid function tests 
X 
 
 
Calculated CrCl 
X 
 
Urinalysis 
X 
 
TDV and Follow Up Disease Assessments 
Tumor 
Imaging/Response 
Assessment4 
X 
 
4. At the TDV, CT scan is required only if the last disease assessment did not show PD and was performed ≥6 
weeks before TDV. For participants who discontinue study treatment without documented disease progression, 
every effort should be made to continue monitoring disease status by tumor imaging using the same imaging 
schedule used while on treatment until the start of a new anticancer treatment, disease progression, pregnancy, 
death, withdrawal of consent, or the end of the study, whichever occurs first. See additional information in 
Section 9.3.1. 
Telephone call for 
 
X* 
*Follow up for survival is no longer required for participants in this arm.  


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TDV and Follow Up 
Assessments 
Treatment 
Discontinuation Visit 
 
Survival 
Follow-Up 
Notes 
Visit Window 
+ 10 days 
 
 
survival status1a 
TDV and Follow Up Tumor Biopsies 
Fresh tumor tissue 
sample 
X5 
 
5. If possible, obtain an optional tumor tissue sample at time of confirmed PD or PR. 
TDV and Follow Up Patient-Reported Outcomes/Health-Related Quality of Life: Part 2 ONLY 
 
 
 
 
 
 
 
 
 
 
 
TDV and Follow Up Biomarkers10 
TDV and Follow Up Pharmacokinetics and Anti-Drug Antibodies (ADA)9 
Feladilimab 
(GSK3359609) ADA 
 
X7,8 
7. To be collected 30 days post last dose and 12 weeks post last dose. 
8. In the event of hypersensitivity reaction that is clinically significant and/or leads to study treatment 
discontinuation, an additional sample should be collected at 24 weeks post last dose of study treatment. 
9. Collection of follow up PK and ADA samples is no longer required for ongoing participants in this arm. 
Feladilimab 
(GSK3359609) PK 
 
X7 
Ipilimumab ADA  
 
X7,8 
Ipilimumab PK 
 
X7 
Abbreviations: ADA = Anti-drug antibody; AE = Adverse event; AESI = Adverse events of special interest; β-hCG = Beta-human chorionic gonadotropin; CR = complete 
response; CrCl = Creatinine clearance; CT = computed tomography; CTCAE = Common Terminology Criteria for Adverse Events; ECOG PS = Eastern Cooperative Oncology 
Group performance status; eCRF = Electronic case report form; 
 
; 
 
 
; PD = Progressive Disease; PGRS = Patient Global Rating of Severity, 
 
; PR = Partial response; 
 
 SAE = Serious adverse event; TDV = Treatment Discontinuation Visit 
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12.1.3.3. 
Rationale for the ICOS Agonist/Ipilimumab Combination 
Ipilimumab is a recombinant, human monoclonal IgG1 kappa antibody that binds to 
CTLA-4. CTLA-4 is a negative regulator of T-cell activity. Ipilimumab is a monoclonal 
antibody that binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, 
CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and 
proliferation, including the activation and proliferation of tumor infiltrating T-effector 
cells. Inhibition of CTLA-4 signaling can also reduce T-regulatory cell function, which 
may contribute to a general increase in T cell responsiveness, including the anti-tumor 
immune response [YERVOY Prescribing Information, 2020]. Yervoy (ipilimumab) alone 
and in combination with nivolumab  platinum-based chemotherapy is indicated for the 
treatment of patients across a number of indications which include metastatic melanoma 
and NSCLC. 
Inducible t-cell costimulator (ICOS) is a co-stimulatory receptor belonging to the 
CD28/CTLA immunoglobulin super family with expression restricted to T cells [Hutloff, 
1999]. ICOS is weakly expressed on resting TH17, follicular helper T and Treg cells yet 
is highly induced on CD4+ and CD8+ T cells upon T cell receptor (TCR) engagement 
and activation [Paulos, 2010; Wakamatsu, 2013]. Upregulation of ICOS leads to both 
Th1 and Th2 cytokine secretion and sustained effector T cell proliferation and function 
[Sharpe, 2002]. A growing body of evidence supports the concept that activating ICOS 
on CD4+ and CD8+ effector T cells has antitumor potential. 
The rationale for targeting ICOS in cancer has been established by multiple lines of 
nonclinical and clinical evidence. Engagement of the ICOS pathway with an ICOS-L-Fc 
fusion protein is shown to have potent antitumor activity in multiple syngeneic mouse 
tumor models [Ara, 2003]. Emerging data from patients treated with anti-CTLA-4 
antibodies suggest a positive role of ICOS+ effector T cells in mediating an antitumor 
immune response. Patients with metastatic melanoma [Di Giacomo, 2013], urothelial 
[Carthon, 2010], breast [Vonderheide, 2010] and prostate cancer [Chen, 2009] who have 
increased absolute counts of circulating and tumor infiltrating CD4+ICOS+ and 
CD8+ICOS+ T cells after ipilimumab treatment have significantly better treatment 
related outcomes than patients where little or no increases are observed. Importantly, it 
was shown that ipilimumab changes the ICOS+ T effector-to-Treg cell ratio, reversing an 
abundance of Tregs cell pre-treatment to a significant abundance of T effectors vs. Tregs 
cells relative to cells following treatment [Liakou, 2008; Vonderheide, 2010]. As 
evidenced by the clinical data, ICOS+ T effector cells may be a positive predictive 
biomarker of ipilimumab response, and activation of this population of cells with an 
ICOS agonist antibody may confer an advantage by mounting a more robust immune 
antitumor response. 
The T cell activating potential of feladilimab was evaluated in multiple assay formats as a 
single agent and in combination with other immune checkpoint inhibitors. Ex-vivo 
studies were conducted with PBMC isolated from healthy human donors pre-activated 
with anti-CD3 alone or anti-CD3/anti-CD28. Soluble feladilimab either alone or in 
combination with ipilimumab demonstrated a more robust pro-inflammatory cytokine 
response than either single agent alone. A modified allogenic mixed lymphocyte reaction 
(MLR) assay, where lymphocytes from one donor were mixed ex-vivo with peptide-


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stimulated dendritic cells differentiated from freshly isolated monocytes from another 
donor, was also employed to evaluate feladilimab in combination with ipilimumab. 
Significant increases in IFNγ secretion were observed for feladilimab combined with 
ipilimumab as compared to either agent alone, supporting clinical evaluation of this 
combination.  
In vivo studies using ICOS-/- and ICOS-ligand (L)-/- mice demonstrated the requirement 
of ICOS signaling in mediating the anti-tumor activity of an anti-CTLA-4 antibody in the 
B16/F10 melanoma syngeneic tumor model [Fu, 2011]. Mice lacking ICOS or ICOS-L 
had significantly decreased survival rates compared to wild-type mice after anti-CTLA-4 
antibody treatment suggesting a combination of anti-CTLA-4 treatment with an anti-
ICOS agonist may provide robust anti-tumor responses. In a separate study, B16 tumors 
engineered to overexpress ICOS-L were found to be significantly more sensitive to anti-
CTLA-4 treatment as compared to a B16/Bl6 tumor cells transduced with a control 
protein [Fan, 2014]. Treatment with mouse anti-CTLA-4 mouse antibody induced ICOS 
on CD4+ and CD8+ T cells in the tumor, spleen and blood, a pattern comparable to the 
ipilimumab clinical response showing that interplay between receptor induction extended 
to CTLA-4.  
To support the combination of feladilimab with ipilimumab (anti-CTLA-4 mAb), the 
nonclinical toxicology findings of ipilimumab as a single agent was reviewed. The 
nonclinical toxicology profiles of ipilimumab is well characterized and indicates that 
combination toxicology studies in monkeys would not likely provide any relevant data 
that would inform clinical risk assessments. Risk mitigation measures for potential 
clinically relevant risks associated with feladilimab combination therapy based on these 
nonclinical assessments or clinical safety data are described in this protocol. In 
intravenous repeat-dose toxicology studies in monkeys, ipilimumab was generally well 
tolerated. Immune-mediated adverse reactions were observed infrequently and included 
colitis (which resulted in a single fatality), dermatitis and infusion reaction (possibly due 
to acute cytokine release resulting from a rapid injection rate) [Hanaizi, 2012]. In a 
monkey reproductive toxicology study, administration of ipilimumab to cynomolgus 
monkeys from the onset of organogenesis through delivery resulted in higher incidences 
of abortion, stillbirth, premature delivery (with corresponding lower birth weight), and 
higher incidences of infant mortality in a dose-related manner. The clinical relevance of 
these findings are well characterized and risk mitigation measures are described in this 
protocol.  
Refer to the GSK3359609 Investigator’s Brochure (IB) [GSK Document Number 
2017N319717_03; 2020] for further details.  
 
 
 
 


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12.1.3.4. 
Clinical Safety Summary  
12.1.3.4.1. Feladilimab  
As of the feladilimab Investigator Brochure data cutoff date of 16 March 2020, 249 
participants received at least 1 dose of monotherapy feladilimab in study 204691 at the 
following dose levels: 0.001 mg/kg (n=1), 0.003 mg/kg (n=1), 0.01 mg/kg (n=2), 0.03 
mg/kg (n=7), 0.10 mg/kg (n=25), 0.30 mg/kg (n=56), 1.0 mg/kg (n=126), 3.0 mg/kg 
(n=24), and 10 .0 mg/kg (n=7). In these 249 participants, the most common AEs 
(occurring in 15% of participants overall regardless of dose level or relationship) were 
anemia (22%), asthenia (21%), nausea (19%), fatigue (18%), diarrhea (16%), and 
vomiting (15%).  
Refer to GSK3359609 IB [GSK Document Number 2017N319717_03] for further 
details.  
12.1.3.4.2. Ipilimumab  
The most common adverse reactions (5%) with ipilimumab as a single agent are fatigue, 
diarrhea, pruritis, rash, and colitis. The most common adverse reactions (20%) with 
ipilimumab in combination with nivolumab are fatigue, rash, pruritis, diarrhea, 
musculoskeletal pain, cough, pyrexia, decreased appetite, nausea, abdominal pain, 
arthralgia, headache, vomiting, dyspnea, dizziness, hypothyroidism, and decreased 
weight. 
For more details on specific indications, adverse reactions and ipilimumab dosage refer to 
the prescribing information [YERVOY Prescribing Information, 2020]. 
 
12.1.3.5. 
Dose Justification 
12.1.3.5.1. Feladilimab Pharmacokinetics and Pharmacodynamics 
The PK of feladilimab was evaluated after 30 minutes of IV infusion at doses from 0.001 
mg/kg to 10.0 mg/kg every 3 weeks (Q3W) in participants with solid tumors in Study 
204691. The plasma PK samples (received prior to the 2020 IB update cutoff date of 16 
March 2020) were analyzed with a validated bioanalytical method with a LLOQ of 0.1 
µg/mL. 
As of 16 March 2020, preliminary PK data in monotherapy cohorts were available in 1 
participant at 0.003 mg/kg, 2 participants at 0.01 mg/kg, 7 participants at 0.03 mg/kg, 25 
participants at 0.1 mg/kg, 52 participants at 0.3 mg/kg, 123 participants at 1.0 mg/kg, 23 
participants at 3.0 mg/kg, and 7 participants at 10.0 mg/kg dose. Preliminary PK data in 
pembrolizumab combination cohorts were available in 5 participants at 0.01 mg/kg, 
5 participants at 0.03 mg/kg, 13 participants at 0.1 mg/kg, 244 participants at 0.3 mg/kg, 
38 participants at 1.0 mg/kg, and 18 participants at 3.0 mg/kg dose. Preliminary PK data 
in GSK3174998 combination cohorts were available in 5 participants each at 8 and 24 mg 
and 1 participant at 80 mg fixed dose. Preliminary PK data in chemotherapy combination 


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cohorts of the safety run-in were available in 55 participants at 80 mg fixed dose of 
feladilimab.  
Based on these preliminary data, the median plasma concentration-time profiles of 
feladilimab exhibit a bi-exponential decline. There are no changes in feladilimab PK 
when co-administered at doses from 0.01 to 3.0 mg/kg with biologic or chemotherapy 
partners. Furthermore, median feladilimab plasma PK profiles after dosing at 8, 24, and 
80 mg fixed doses were superimposable to the median PK profiles observed with 0.1, 0.3, 
and 1.0 mg/kg doses. Preliminary plasma PK parameters of feladilimab computed using 
noncompartmental analysis methods (AUC, C, and Cmax) calculated over the first dosing 
interval (up to 503 hours) exhibit approximate dose proportional increases in feladilimab 
exposure over the range of 0.01 to 10.0 mg/kg doses. Observed exposures (AUC and C) 
from body-weight based dose of 1.0 mg/kg (combined monotherapy and combination 
cohorts) and corresponding fixed dose equivalent of 80 mg (chemotherapy safety run-in) 
overlap with each other, indicating similar exposures can be achieved with a fixed dosing 
regimen. Preliminary population PK estimated geometric mean systemic half-life (t1/2) of 
feladilimab is approximately 19 days.  
Based on the preliminary data, median CD4 and CD8 receptor occupancy was maintained 
at or above 70% during the dosing interval of first cycle for doses 0.3 mg/kg as shown 
in Figure 8.  
Refer to GSK3359609 IB [GSK Document Number 2017N319717_03] for further 
details.  


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Figure 8 
Median CD4+ and CD8+ Receptor Occupancy (%RO) During the First 
Cycle of Feladilimab Administration as Monotherapy 
 
Feladilimab Dosing Frequency 
The systemic half-life of feladilimab is approximately 19 days based on the preliminary 
population PK analysis of data from ongoing study 204691. The existing feladilimab 


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Q3W regimen in the ongoing clinical study is also consistent with the Q3W dosing 
regimen typical with other IgG4 based monoclonal antibody therapies. Thus, feladilimab 
will be dosed Q3W in combination with ipilimumab. Combination of feladilimab with 
any other treatment in other arms of this study may have a different dosing regimen as 
deemed appropriate.  
Rationale for Fixed Dose 
Therapeutic monoclonal antibodies are often dosed based on body-size due to the concept 
that this reduces inter-participant variability in drug exposure. However, body-weight 
dependency of PK parameters does not always explain all or even a majority of observed 
variability in the exposure of monoclonal antibodies [Zhao, 2017]. Hence, the selection 
of body-weight based versus fixed dosing in this study was evaluated through population 
PK modelling and simulation efforts.  
A preliminary population PK model (N = 637 participants; March 2020), which 
characterized the influence of body weight, age, and other participant covariates on 
exposure was developed. Results of this analysis indicate a feladilimab fixed dose is 
appropriate for trial participants across the bodyweight spectrum. Simulations show a 
feladilimab body weight-based dose results in slightly higher exposure in heavier weight 
participants and a feladilimab fixed dose results in slightly higher exposures in lighter 
participants. However, the range of exposures are similar between body-weight based and 
fixed dosing across the entire body weight spectrum and the exposures are maintained 
well within established clinical boundaries of safety at doses in the range of 24 to 80 mg 
Q3W (the highest studied dose in monotherapy deemed tolerable was 10 mg/kg or ~800 
mg). This suggests that there is no advantage of body-weight based dosing over fixed 
dosing and that lighter patients will not be more susceptible to treatment-related adverse 
events arising from marginal increases in exposure.  
Overall, these preliminary population PK simulations indicate that using fixed dosing 
would result in a similar range of exposures as that of body weight-based dosing. Also, 
fixed dosing offers the advantage of reduced dosing errors, reduced drug wastage, 
shortened preparation time, and improved ease of administration. Thus, a feladilimab 
fixed dose based on a reference body weight of 80 kg is reasonable and appropriate. 
Refer to GSK3359609 IB [GSK Document Number 2017N319717_03] for further 
details.  
12.1.3.5.2. Feladilimab Dose Rationale (Arm 3) 
Based on the preliminary PK data described above in Section 12.1.3.5.1 and target 
engagement shown in Figure 8, median CD4 and CD8 receptor occupancy was 
maintained at or above 70% during the dosing interval of first cycle for doses ≥0.3 
mg/kg. Sufficiently high CD4+ RO is expected at peak exposures (89% to >99% RO) as 
well as at trough exposures (69% to >99% RO) at steady-state with the proposed 24 mg 
dose in arm 3. 
Collectively, based on the safety and exposure data from the Phase 1 study and the 
predicted target engagement, a 24-mg dose will be evaluated in combination with 


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ipilimumab in this study. No drug-drug interaction related changes are expected in 
feladilimab PK with ipilimumab co-administration. The currently planned feladilimab 
dose for this arm is the same as that used in the phase II/III studies for recurrent or 
metastatic (R/M) head and neck squamous cell carcinoma/cancer (HNSCC). 
12.1.3.5.3. Ipilimumab Dose Rationale 
The dose for ipilimumab for this study is 1 mg/kg or 3 mg/kg administered intravenously 
every 3 weeks. 
The 1 mg/kg or 3 mg/kg doses were selected based on approvals in multiple tumor types, 
both as monotherapy and in combination with nivolumab. [YERVOY Prescribing 
Information, 2020]. 


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12.1.3.6. 
Study Treatments 
Table 22 
Description and Administration of Arm 3 Study Treatments 
Name 
Ipilimumab 
Feladilimab (GSK3359609; 
ICOS agonist)  
Description 
CTLA-4 inhibitor 
Humanized anti-ICOS IgG4 
mAb 
Dosage form/strength 
50 mg/ 10 mL Solution;  
5 mg/mL 
Solution for injection/ 10 mg/mL  
Dosage 
1 mg/kg, 
3 mg/kg 
24 mg 
Route of administration 
IV infusion 
IV infusiona 
Dosing instructionsa/frequency 
Administer diluted product/once 
Q3W (refer to SRM for infusion 
time) 
Administer diluted product/once 
Q3W 
a: The study reference manual contains the details on product handling, storage, preparation, and administration. 
In the ipilimumab + feladilimab containing arm, feladilimab will be administered first as 
a 30minute IV infusion (infusion time may be adjusted in the event an infusion reaction 
occurs) under medical supervision of an investigator or designee. The administration of 
the ipilimumab must be started at least 30 minutes and no more than one hour following 
the end of the feladilimab infusion under medical supervision of an investigator or 
designee.  
Participants should remain under observation at the study site post-study treatment 
infusion per the judgement of the investigator or as per institutional guidelines. Refer to 
Section 12.1.3.10, Table 24 for details on the management of participants experiencing 
infusion reactions. 
 
The date(s), start time(s) and stop time(s) of administration of each study drug will be 
documented in the source documents and reported in the eCRF. The dose of study 
treatment and study participant identification will be confirmed at the time of dosing by a 
member of the study site staff other than the person administering the study treatment. 
Infusions may be administered up to 72 hours before or after the planned date of 
treatment for administrative reasons only (e.g., scheduling an infusion around a holiday). 
The 72-hour window does not apply to completion of study treatment administration 
interrupted by an infusion reaction. Refer to Section 7.2.1.4 for criteria governing dose 
interruptions or delays.  
Details on preparation and administration of feladilimab and ipilimumab are described in 
the study reference manual (SRM) and ipilimumab package insert, respectively.  


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12.1.3.7. 
Concomitant Therapy 
Please refer to Section 7.7  
12.1.3.8. 
Treatment of Overdose 
12.1.3.8.1. Feladilimab Overdose 
An overdose of feladilimab is defined as administration of a dose that is >240 mg (>10 
times the 24 mg intended dose). In the event of an overdose, the investigator must: 
1. Contact the Medical Monitor immediately. 
2. Closely monitor the participant for adverse events and laboratory abnormalities 
for at least 130 days from the date of the overdose. 
3. Obtain a plasma sample for PK analysis within 28 days from the date of the last 
dose of study treatment if requested by the Medical Monitor (determined on a 
case-by-case basis).  
4. Document the quantity of the excess dose as well as the duration of the 
overdosing in the eCRF.  
Decisions regarding dose interruptions or modifications will be made by the investigator 
in consultation with the Medical Monitor based on the clinical evaluation of the 
participant.  
There is no specific antidote for overdose with the experimental treatments being 
evaluated in this study. In the event of a suspected overdose, it is recommended that the 
appropriate supportive clinical care be instituted as dictated by the participant’s clinical 
status.  
12.1.3.8.2. Ipilimumab Overdose 
According to ipilimumab prescribing information, no information is available on 
overdosage. In case of overdose symptomatic treatment has to be applied; there are no 
known antidotes for the compound. 
In the event of an overdose, the investigator must: 
1. Contact the Medical Monitor immediately. 
2. Closely monitor the participant for adverse events and laboratory abnormalities 
for at least 130 days from the date of the overdose. 
3. Obtain a sample for PK analysis within 28 days from the date of the last dose of 
study treatment if requested by the Medical Monitor (determined on a case-by-
case basis). 
4. Document the quantity of the excess dose as well as the duration of the 
overdosing in the eCRF. 


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Decisions regarding dose interruptions or modifications will be made by the investigator 
in consultation with the Medical Monitor based on the clinical evaluation of the 
participant. 
12.1.3.9. 
 Treatment Duration for Ipilimumab 
Participants enrolled will be treated until disease progression, intolerable toxicity, 
informed consent withdrawal or death. Combination study treatment will continue to be 
administered at the indicated schedule for a maximum duration of approximately 2 years 
or up to 35 treatment visits, whichever comes first. Refer to Section 5.2. for additional 
details regarding follow up after discontinuation of study treatment. 
12.1.3.10. Dose modification and Management Guidelines 
The dose of feladilimab cannot be reduced or modified.  
No dose reductions are allowed for ipilimumab. Dose Modification Guidelines for 
immune related Adverse Events are listed in Section 7.2.1.1.  
If either GSK3359606 or ipilimumab is held or discontinued for any toxicity, the other 
study drug must also be held or discontinued, unless discussed otherwise with Medical 
Monitor. 
12.1.3.10.1. 
General Guidelines for Immune-Related Adverse Events (irAEs) 
AEs associated with immunotherapy treatment may be immune-mediated. These 
immune-related AEs (irAEs) may occur shortly after the first dose or several months after 
the last dose of treatment, or during the treatment course, and may affect more than one 
body system simultaneously. Therefore, early recognition of and initiation of treatment 
for these events is critical to reduce potential complications. Based on existing data from 
the study 204691, most treatment-related AEs were Grade 1 or 2, managed with 
supportive care and if appropriate the administration of corticosteroids. 
For suspected irAEs, ensure adequate evaluation to confirm the etiology or exclude other 
causes. Additional procedures or tests such as, but not limited to, bronchoscopy, 
endoscopy, or skin biopsy may be included as part of the evaluation. Based on the 
severity of irAEs, withhold or permanently discontinue treatment and administer 
corticosteroids. Dose modification and toxicity management guidelines for irAEs 
associated with immunotherapies are provided in Table 23.  
Table 23 
Dose Modification and Toxicity Management Guidelines for Immune-
Related AEs 
General instructions: 
• 
Corticosteroid taper should be initiated upon AE improving to Grade 1 or less and continue to taper over at 
least 4 weeks. 
• 
For situations where immunotherapy treatment has been withheld, treatment can be resumed after AE has 
been reduced to Grade 1 or 0 and corticosteroid has been tapered. Immunotherapy treatment should be 
permanently discontinued if AE does not resolve within 12 weeks of last dose or corticosteroids cannot be 
reduced to ≤ 10 mg prednisone or equivalent per day within 12 weeks.  
• 
For severe and life-threatening irAEs, IV corticosteroid should be initiated first followed by oral steroid. Other 
immunosuppressive treatment should be initiated if irAEs cannot be controlled by corticosteroids. 


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


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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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12.1.3.10.2. 
Dose Modification and Toxicity Management of Infusion-Reactions 
Related to Immunotherapy Treatment 
Table 24 
Immunotherapy Infusion Reaction Dose Modification and Treatment 
Guidelines 
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.
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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12.1.3.10.3. 
Adverse Events of Special Interest (AESI) 
AESI are defined as events of potential immunologic etiology, including irAEs. Such 
events recently reported after treatment with other immune modulatory therapy include, 
but are not limited to, the following: pneumonitis, nephritis, hepatitis, colitis, immune 
related endocrinopathies (such as thyroiditis or hypophysitis) or immune related 
cutaneous toxicities, to include rashes confirmed via biopsy to be immune-mediated.  
AESIs will be reported within 24 hours if the event meets the criteria for a serious event.  
12.1.3.11. Safety Evaluation 
All the regimen qualification activities in Part 1 are based on the premise that a proposed 
dose for each component, informed by prior experience, will be evaluated to go forward 
to Part 2. If the Part 1 regimen qualification process confirms the dose combination, the 
combination will proceed to Part 2. If the Part 1 regimen qualification process does not 
confirm the dose combination, further evaluation in the 205801 platform study of that 
combination will stop. 
 
The combination cohort of feladilimab with ipilimumab will test 24 mg feladilimab in 
combination with either 1mg/kg ipilimumab or 3mg/kg ipilimumab. The arm assessing 
the combination of 24 mg feladilimab with 1 mg/kg ipilimumab will be conducted 
independently from the arm assessing the combination of 3 mg/kg ipilimumab with 24 
mg feladilimab. There will be no dose escalation or de-escalation for either combination 
partner. Further evaluation of a combination demonstrated to result in toxicity as 
described in Table 27 at the rate defined in Table 25, will be stopped.  
 
Safety and tolerability will be guided using a modified toxicity probability interval 
(mTPI) approach with some additional modifications due to only one dose level being 
evaluated. The mTPI design is an extension of the toxicity probability interval method 
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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and employs a simple beta-binomial hierarchic model [Ji, 2010]. Decision rules are based 
on calculating the unit probability mass (UPM) of three intervals corresponding to under 
dosing, proper dosing, and overdosing in terms of toxicity. Specifically, the under-dosing 
interval is defined as (0, pT – ε1), the overdosing interval as (pT + ε2, 1), and the proper 
dosing interval as (pT – ε1, pT + ε2), where pT is the target toxicity rate, ε1 and ε2 are 
small fractions, such as 0.05, to account for the uncertainty around the true target toxicity. 
The three dosing intervals are associated with three different dose decisions. Given an 
interval and a probability distribution, the UPM of that interval is defined as the 
probability of the interval divided by the length of the interval. The mTPI design 
calculates the UPMs for the three dosing intervals, and the one with the largest UPM 
implies the corresponding dose-finding decision. For example, if the over-dosing interval 
has the largest UPM, decision will be to stop further evaluation.  
 
Initial safety and tolerability of the combination will be evaluated within the first 21 days 
(DLT period). Evaluation of the available safety data over the first 21 days of treatment 
for each participant enrolled is required from at least 3 participants before a decision is 
made to enroll additional participants. The maximum number of participants assigned to 
either dose level will be at the discretion of the Sponsor in consultation with the 
investigators. If no more than one of the first three participants treated with 24 mg 
feladilimab + 1 mg/kg ipilimumab experience safety findings (DLTs) meeting the criteria 
described in Table 27, an additional 6-7 participants will be treated with 24 mg 
feladilimab + 1mg/kg ipilimumab.  
If a participant withdraws from the study before the completion of the 21-day DLT 
evaluation period for reasons other than DLT, then the participant may be replaced to 
achieve the three-participant required minimum. The decision to declare the combination 
tolerable will occur following review of the safety, PK and PD data and joint discussion 
by the GSK Medical Monitor and investigators. Membership, roles and accountabilities, 
and the process for safety review and meeting frequency is outlined in the Study 
Reference Manual.  
The mTPI design assumptions include the following: 
(i) 
A maximum of 10 participants will complete the DLT evaluation period; 
(ii) 
The true underlying toxicity rate for feladilimab falls within the range from 25% 
to 33% and targets at 30%. 
(iii) 
Maximum probability that the dose exceeds the target toxicity is 95%; however an 
additional safety rule will be applied if the maximum sample size of 10 is reached 
whereby the dose will be considered non-tolerated if there is greater than 70% 
posterior probability that the true DLT rate is >30% 
Participants will be enrolled in cohorts of 3-4 and decisions will be made after all patients 
within a cohort complete the DLT evaluation period.  
The monitoring rules guiding dose decision are provided in Table 25. The tolerability 
decision framework using the mTPI method were generated based on a beta/binomial 
model and pre-calculated before study initiation. The entries in the Dose Decision Rules 
table below represent dose-finding decision points at which a determination is made 


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whether the combination remains safe for continued testing using the data generated in 
the cohort of interest.. In other studies utilizing mTPI, these points are often denoted as 
“E”, “S”, and “D”, denoting the thresholds governing escalating the dose, staying at the 
same dose, or de-escalating the dose, respectively. However in this study, as there is no 
dose escalation or de-escalation, the thresholds mark the criteria used to determine 
whether the doses of the combination are tolerated and therefore, permit continued 
treatment of additional participants at the same combination dose. If a dose combination 
is not tolerated per Table 25 and Table 27, further evaluation of that dose combination 
will be stopped without exploration of other dose levels of either or both combination 
partners.  
As an example, the scenario in which one of the first three participants in Part 1 
experience a DLT is represented in the cell marking the intersections of row ‘1’ and 
column ‘3’ in Table 25. According to the model underlying the mTPI, such a scenario 
predicts the actual rate of toxicity to be within the acceptable, predetermined range, 
therefore allowing treatment of additional three participants at the same dose 
combination. The scenario in which one of these three additional participants experience 
DLT, is represented in the cell marking the intersection of row ‘2’ and column ‘6’, 
allowing treatment of an additional four participants according to the model. If two of 
these four additional participants experience DLTs, the combination will not be 
considered as tolerated and no additional participants will be treated in this combination. 
not continue because of unacceptable toxicity. If the combination is considered tolerated, 
additional participants will be enrolled to further evaluate safety and PK/PD. No formal 
evaluation of DLTs will be performed after the 21 day period, however other measures of 
safety will continue to be monitored. 


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Table 25 
Dose Decision Rules 
  
Number Treated 
  
  
#DLTs 
3 
6 
10 
0 
Tolerated 
Not applicable 
Not applicable 
1 
Enroll 3 
Tolerated 
Tolerated 
2 
Stop 
Enroll 4 
Tolerated 
3 
Stop 
Stop 
Tolerated 
4 
  
Stop 
Stop 
5 
  
Stop 
Stop 
6 
  
Stop 
Stop 
7 
  
  
Stop 
8 
  
  
Stop 
9 
  
  
Stop 
10 
  
  
Stop 
 
12.1.3.12. Futility evaluation 
Once an arm transitions through the initial safety evaluation as described above, 
additional participants will be enrolled to that arm, up to a maximum of 15 participants to 
provide further evaluation of safety and tolerability and: 
1. Preliminary PK/pharmacodynamic characteristics (i.e., measures of target 
engagement and functional effects such as receptor occupancy and cytokine 
release) and 
2. Evaluation of antitumor activity. 
In these participants, tumor biopsy at Screening and Week 7 will be required (refer to 
SOA tables for each arm Section 12.1 or further details).  
An interim evaluation of futility in terms of ORR will be conducted after the first 10 
participants have had at least two post baseline RECIST assessments. A maximum of 15 
participants will be enrolled to allow for 10 evaluable participants to be assessed for 
futility. If no objective responses are observed in 10 evaluable participants, development 
of the experimental regimen may be stopped. Decisions will be made after evaluation of 
other endpoints and will be based on the totality of data, including the Disease Control 
Rate endpoint. 


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Table 26 
Planned Dose Levels for Feladilimab and Ipilimumab  
Dose Level 
Ipilimumab (mg/kg) 
Feladilimab 
(GSK3356909) (mg) 
Safety (n) 
PK/PD (n) 
Total (n) 
1 
1 
24 
3-6 
6-19 
9-25 
2 
3 
24 
3-10 
N/A 
3-10 
 
The ipilimumab combination cohort will initiate at the 3mg/kg dose in combination with 
feladilimab 24 mg. If the 3mg/kg ipilimumab dose meets the dose limiting toxicity 
definition as described below, a second cohort of 3-10 participants will be dosed at 
1mg/kg ipilimumab plus 24 mg feladilimab to explore a lower dose.  
12.1.3.13. Dose Limiting Toxicity 
The severity of all toxicities will be graded using National Cancer Institute - Common 
Terminology Criteria for Adverse Events (NCI-CTCAE) (version 5.0) [NCI, 2017]. The 
DLT observation period is 21 days in length and begins on the day feladilimab is first 
administrated to the participant. 
 
A DLT is defined as an AE that meets at least one of the criteria listed in Table 27 and is 
considered by the investigator to be clinically relevant and attributed (probably or 
possibly) to the study treatment during the 21-day DLT observation period. An AE 
considered related to the underlying disease under study it is not defined as a DLT. A 
safety event can still be included for DLT consideration after the 21 day window. 
 
Table 27 
Dose-Limiting Toxicity Criteria 
Toxicity 
DLT Definition 
Hematologic 
• Febrile neutropenia as defined by CTCAE v5 
• Grade 4 neutropenia of >7 days in duration or requiring G-CSF 
• Grade 4 anemia of any duration  
• Grade 4 thrombocytopenia of any duration or Grade 3 thrombocytopenia with bleeding 
Non- hematologic 
• Grade 4 toxicity 
• Grade 3 pneumonitis of any duration 
• Grade 3 toxicity that does not resolve to ≤Grade 1 or baseline within 3 days despite optimal 
supportive carea 
• Any Grade 2 ocular toxicity requiring systemic steroids, or any ≥ Grade 3 ocular toxicity 
• Following events are not considered DLTs 
o Grade 3 and Grade 4 asymptomatic electrolyte abnormalities that are corrected within 24 
hours without clinical sequelae 
o Grade 3 nausea, vomiting, or fatigue that resolves to Grade 1 within 7 days with optimal 
supportive care 
o Grade 3 and Grade 4 infusion reactions in participants not receiving prophylaxis for IRRs 
(refer to Section 7.2.1.2 for details on IRR management)  


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Toxicity 
DLT Definition 
Other 
• Toxicity that results in permanent discontinuation of feladilimab monotherapy or feladilimab 
and agent in combination during the first four weeks of treatment 
• Grade 3/Grade 4 toxicity that results in a participant not receiving the expected doses of a 
regimen in Cycle 1, defined by 21 days 
• Any other toxicity considered to be dose-limiting that occurs beyond four weeks will be 
considered in the selection of the dose to recommend for expansion cohorts 
• Any other event which in the judgment of the investigator and GSK Medical Monitor is 
considered to be a DLT 
a. Suggested toxicity management guidelines as described in Section 7.2.1.2 may include systemic corticosteroids 
for immune-related toxicities; if systemic corticosteroids use delays administration of the second dose of study 
treatment and the event does not otherwise meet the DLT criteria for non- hematologic toxicity, the dose delay 
will not be considered a DLT.  
CTCAE=Common Toxicity Criteria for Adverse Events; DLT = Dose-limiting toxicity; G-CSF =Granulocyte colony-
stimulating factor; GSK =GlaxoSmithKline; IRR=infusion related reaction 
 
If a participant experiences a DLT during the DLT observation period, the participant 
may resume dosing provided the toxicity did not meet study treatment discontinuation 
criteria and following approval by the Sponsor. In cases where retreatment is considered, 
refer to Section 12.1.3.10.1 for selection of the dose and schedule of ipilimumab in 
combination with feladilimab. Participants may reduce the dose intensity of ipilimumab 
one or two times.  
 
Toxicity management and dose modification guidelines described in Section 7.2.1.2 are 
provided for those AEs of special interest that, although not observed in nonclinical 
studies, may be expected with the administration of immune directed therapies such as 
feladilimab and ipilimumab.  
 
Guidance for the identification, evaluation, and the established algorithms for the 
treatment management of immune-related adverse events (irAEs) including dose 
modification algorithms are provided in Section 7.1 and Section 7.2. These guidelines are 
based on the experience of irAE management following the development of immune 
check-point inhibitors such as ipilimumab and pembrolizumab.  
 
If there is a delay in administration of study treatment, refer to Section 7.2.1.4 for 
guidance on planning of subsequent study visits. 
 
12.1.3.14. Risk-Benefit Assessment for Ipilimumab combined with Feladilimab 
Feladilimab is intended to be a first-in-class anti-ICOS agonist antibody for the treatment 
of cancers of different histology. It is expected to differentiate from first generation 
immunomodulatory antibodies directed against Cytotoxic T-Lymphocyte-Associated 
Protein 4 (CTLA-4) and Programmed cell death protein 1 (PD-1)/PD-Ligand-1 (PD-L1) 
by targeting a different axis in the antitumor T cell response cascade and promoting 
activation of a co-stimulatory receptor instead of blocking an inhibitory checkpoint 
receptor. The effect of ICOS agonist activity is to promote the expansion and function of 
cytotoxic CD8+, and effector CD4+ T cells, resulting in improved antitumor immune 
responses that are durable. Due to the restricted expression of ICOS on activated T cells, 
it is expected that feladilimab may result in a more favorable safety profile as compared 


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with other antibodies that target co-stimulatory T cell receptors constitutively expressed 
on naïve T cells. 
Nevertheless, some tumors may engage multiple mechanisms to escape immune-
mediated antitumor effects thus combining an ICOS agonist with agents that target 
different pathways within the immune cascade may be required for achieving the desired 
clinical effect. Accordingly, as ICOS agonists stimulate IFN  production which induces 
PD-L1 expression on tumor cells and within the tumor microenvironment [Mimura, 
2018], this may facilitate the therapeutic benefit of PD-1/L1 blockade within tumors that 
have low levels of PDL1 expression. Several studies have underscored the co-expression 
of PD-1 and ICOS on tumor--infiltrating lymphocytes (TILs) and anti-PD-1-responsive 
peripheral T cells, as well as complementarity between inhibition of the PD-1/L1 axis and 
co-stimulation via the ICOS/L axis [Kamphorst, 2017; Gros, 2014; Beyrend, 2019]. 
Clinical studies and a series of nonclinical studies support the combination approach of 
an anti-ICOS agonist with immune checkpoint inhibitors or other agents that modulate 
the immune system distinct from ICOS biology. 
Although there is no clinical experience with the combination of feladilimab with 
ipilimumab, given the currently available safety data and the low likelihood of drug-drug 
interactions between feladilimab with ipilimumab, combination therapy may have an 
acceptable safety profile. Additionally, the combination may provide anti-tumor effect in 
participants with advanced NSCLC. The current nonclinical and clinical safety 
information for feladilimab and ipilimumab, used as single agents, provide support for 
their use in combination in the target patient population. 
This is the first study testing the combination of feladilimab with ipilimumab in 
participants with advanced NSCLC that have been treated with standard therapies. Study 
participants may benefit from medical tests and screening performed during the study. 
Any potential benefit of the addition of ipilimumab to feladilimab is unknown. Data 
obtained in this study may help identify individuals more likely to benefit or have side-
effects from ipilimumab plus feladilimab. 
Based on the status of ipilimumab as a marketed product with documented anticancer 
activity and an acceptable safety profile and feladilimab as an agent with close to a one 
thousand patient experience with preliminary signals of activity in NSCLC and a 
manageable toxicity profile, the potential benefit to risk is favorable to proceed with the 
combination in the context of a controlled monitored study with an initial safety 
clearance and rule out futility screening to confirm the potential risks and benefits. 
 
The following sub sections outline the risks and mitigation strategies for this 
protocol for ipilimumab. Refer to the latest ipilimumab US product insert (USPI) and the 
EU SmPC for additional details. Feladilimab risk assessment and mitigation 
strategies are in the master protocol (Section 3.3). 
 


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Table 28 
Risk Assessment and Mitigation Strategy: Ipilimumab 
Potential Risk of 
Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Immune-related 
AEs 
 
 
 
• Inflammatory AEs such as diarrhea/colitis, 
pneumonitis, nephritis, and hepatotoxicity are 
well established as treatment emergent AEs 
with immune-modulating agents and are 
consistent with the immune-stimulatory 
mechanism of action of these agents. (refer to 
the latest SmPC and/or USPI for YERVOY) 
 
• Participants with the following medical 
history are ineligible for this study 
o Toxicity ( Grade 3) related to prior 
immunotherapy leading to study 
treatment discontinuation  
o Active autoimmune disease (refer to 
Section 6.2 exclusion criterion 6) 
o Severe hypersensitivity to another 
mAb 
• Established management algorithms for 
immune-related adverse events (irAEs)  
• Refer to Section 7.2.1.1 for further details 
on the identification, evaluation, and 
management of toxicities with a potential 
immune etiology.  
Infusion and 
hypersensitivity 
reactions and 
potential CRS 
• 
Risk for infusion reactions and 
hypersensitivity is inherent to many mAbs 
[Brennan, 2010] (refer to the latest SmPC 
and/or USPI for YERVOY) 
 
• Participants with history of severe 
hypersensitivity to another mAb or to the 
chemotherapies under investigation 
including any ingredient used in the 
formulation are ineligible for this study.  
• Refer to Section 7.2.1.2 for further details 
on management of infusion reactions.  
• Refer to Section 7.2.1.2 for further details 
on management of CRS 
Immune complex 
disease 
• Immune complex formation and deposition 
findings (refer to the latest SmPC and/or USPI 
for YERVOY) 
• Clinical laboratory safety assessments 
and immunogenicity testing 
 
Table 29 below provides an outline of the risk assessment and mitigation strategy for 
GSK3359609 (feladilimab). More detailed information about the known and expected 
benefits and risks and reasonably expected adverse events of feladilimab may be found in 
the IB [GSK Document Number 2017N319717_03]. 
 
 
 
 
 
 
 
 


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Table 29 
Risk Assessment and Mitigation Strategy GSK3359609 (feladilimab) 
Potential Risk of 
Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Immune-related 
AEs 
 
 
 
• Inflammatory AEs such as diarrhea/colitis, 
pneumonitis, nephritis, and hepatotoxicity are 
well established as treatment emergent AEs 
with immune-modulating agents and are 
consistent with the immune-stimulatory 
mechanism of action of these agents.  
 
• Participants with the following medical 
history are ineligible for this study 
o Toxicity (Grade 3) related to prior 
immunotherapy leading to study 
treatment discontinuation  
o Active autoimmune disease (refer to 
Section 6.2 exclusion criterion 6) 
o Severe hypersensitivity to another 
mAb 
• Established management algorithms for 
immune-related adverse events (irAEs)  
• Refer to Section 7.2.1.1 for further details 
on the identification, evaluation, and 
management of toxicities with a potential 
immune etiology.  
Infusion-related 
reactions (IRRs) 
which include 
hypersensitivity 
and potential 
cytokine release 
syndrome (CRS) 
• Risk for infusion reactions and hypersensitivity 
is inherent to many mAbs [Brennan, 2010]  
• The overall rate of IRRs with feladilimab is low 
and there have been no cases of CRS 
observed across the clinical program of 
feladilimab [GSK Document Number 
2017N319717_03, 2020]. 
 
• Participants with history of severe 
hypersensitivity to another mAb or to the 
chemotherapies under investigation 
including any ingredient used in the 
formulation are ineligible for this study.  
• Refer to Section 7.2.1.2 for further details 
on management of infusion reactions and 
details on CRS management.  
Immune complex 
disease 
• Immune complex formation and deposition 
findings in nonclinical safety studies [GSK 
Document Number 2017N319717_03, 2020] 
• Clinical laboratory safety assessments 
and immunogenicity testing 
Abbreviations: AE = adverse event; IB = Investigator’s Brochure; ICOS = inducible T-cell co-stimulator; LPS = 
lipopolysaccharide; mAb = monoclonal antibody; TCR = T-cell receptor. 
 
12.1.3.15. Additional Study Population Criteria: Arm 3 
None. 


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12.1.3.16. References 
Beyrend, G., et al., PD-L1 blockade engages tumor-infiltrating lymphocytes to co-express 
targetable activating and inhibitory receptors. J Immunother Cancer, 2019. 7(1): p. 217. 
Fan X, Quezada SA, Sepulveda Ma, Sharma P, Allison JP. Engagement of the ICOS 
pathway markedly enhances efficacy of CTLA-4 blockade in cancer immunotherapy. J 
Exp Med. 2014; 211:715-725. 
Fu T, He Q, Sharma P. The ICOS/ICOSL pathway is required for optimal antitumor 
responses mediated by anti-CTLA-4 therapy. Cancer Res. 2011; 71:5445-5454. 
Gros A., et al., PD-1 identifies the patient-specific CD8(+) tumor-reactive 
repertoire infiltrating human tumors. J Clin Invest, 2014. 124(5): p. 2246-59. 
Hanaizi Z, van Zwieten-Boot B, Calvo G, Lopez AS, van Dartel M, Camarero J, et al. 
The European Medicines Agency review of ipilimumab (Yervoy) for the treatment of 
advanced (unresectable or metastatic) melanoma in adults who have received prior 
therapy: summary of the scientific assessment of the Committee for Medicinal Products 
for Human Use. Eur J Cancer, 2012   
Hutloff A, Dittrich AM, Beier KC, Eljaschewitsch B, Kraft R, Anagnostopoulos I, et al. 
ICOS is an inducible T cell co-stimulator structurally and functionally related to CD28. 
Nature. 1999; 397:263-266. 
Kamphorst, A.O., et al., Proliferation of PD-1+ CD8 T cells in peripheral blood after 
PD-1-targeted therapy in lung cancer patients. Proc Natl Acad Sci U S A, 2017. 114(19): 
p. 4993-4998. 
Mimura K., The JL, Okayama H, et al.. PD-L1 expression is mainly regulated by 
interferon gamma associated with JAK-STAT pathway in gastric cancer. Cancer Sci. 
2018; 109: 43-53. 
Sharpe AH, Freeman GJ. The B7-CD28 Superfamily. Nat Rev Immunol. 2002; 2:116- 
126. 
Wakamatsu E1, Mathis D, Benoist C. Convergent and divergent effects of costimulatory 
molecules in conventional and regulatory CD4+ T cells. PNAS. 2013; 110:1023-1028. 
YERVOY [Prescribing Information]. Princeton, NJ. Bristol-Myers Squibb Company; 
2020. 
YERVOY [Summary of Product Characteristics]. Dublin, Ireland. Bristol-Myers Squibb 
Company; 2020. 
 


This section contains detailed information on upcoming sub-studies in this program which are 
currently recruiting. Hence, pages from this section are being removed since they are commercially 
confidential in nature. 

SAP_001.pdf: 
 
CONFIDENTIAL 
 
The GlaxoSmithKline group of companies 
 
205801 
 
1 
 
Division 
: Worldwide Development 
Information Type 
: Reporting and Analysis Plan (RAP) 
 
Title 
: Reporting and Analysis Plan for a Phase II, Randomized, 
Open-label Platform Trial Utilizing a Master Protocol to Study 
Novel Regimens Versus Standard of Care Treatment in 
NSCLC Participants 
Compound Number  : GSK3359609 
Effective Date  
: Refer to Document Date 
 
Description: 
• 
The purpose of this RAP is to describe the planned final analyses and outputs for 
each substudy in the Clinical Study Report (CSR) for 205801. Separate CSRs will be 
produced for each substudy.  
• 
This RAP will be provided to the study team members to convey the content of the 
Statistical Analysis Complete (SAC) deliverable. 
 
RAP Author(s): 
Author 
, 
Junior Statistician, Biostatistics 
 
Statistics Leader, Biostatistics 
 
 
 
 
 
Copyright 2021 the GlaxoSmithKline group of companies. All rights reserved.  
Unauthorised copying or use of this information is prohibited
 
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The GlaxoSmithKline group of companies 
 
205801 
 
2 
 
RAP Team Review Confirmations (Method: E-mail) 
Reviewer 
Date 
 
03-Mar-2021  
Clinical Investigation Lead (Oncology, Clinical) 
 
02-Mar-2021  
Safety Lead (SMG, Pharma Safety) 
 
Physician, ICOS (Oncology) 
05-Mar-2021  
 
Study Data Manager (SDM), Clinical Data Management  
03-Mar-2021  
 
Patients Centered Outcomes, VEO 
04-Mar-2021  
 
02-Mar-2021  
Programming Leader (Oncology, Clinical Programming) 
 
Clinical Statistics & Clinical Programming Line Approvals  (Method: Pharma TMF 
eSignature) 
Approver 
 
 (Biostatistics, GSK) 
 
 Programming (Biostatistics, GSK) 
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TABLE OF CONTENTS 
PAGE 
TABLE OF CONTENTS .................................................................................................. 3 
1. 
INTRODUCTION ...................................................................................................... 7 
2. 
SUMMARY OF KEY PROTOCOL INFORMATION .................................................. 7 
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan ............................ 7 
2.2. 
Study Objective(s) and Endpoint(s)............................................................... 7 
2.3. 
Study Design .............................................................................................. 10 
2.4. 
Statistical Hypotheses / Statistical Analyses ............................................... 12 
2.4.1. 
Hypothesis ................................................................................... 12 
2.4.2. 
Sample Size ................................................................................ 12 
3. 
PLANNED ANALYSES .......................................................................................... 15 
3.1. 
Interim Analyses ......................................................................................... 15 
3.1.1. 
Interim Analyses for Overall Survival (OS) ................................... 15 
3.2. 
Primary and Final Analyses ........................................................................ 16 
4. 
ANALYSIS POPULATIONS ................................................................................... 17 
4.1. 
Protocol Deviations ..................................................................................... 17 
5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA HANDLING 
CONVENTIONS ..................................................................................................... 18 
5.1. 
Study Treatment & Sub-group Display Descriptors ..................................... 18 
5.2. 
Baseline Definitions .................................................................................... 18 
5.3. 
Multicentre Studies ..................................................................................... 18 
5.4. 
Examination of Covariates, Other Strata and Subgroups ............................ 19 
5.4.1. 
Covariates and Other Strata ........................................................ 19 
5.4.2. 
Examination of Subgroups ........................................................... 19 
5.5. 
Multiple Comparisons and Multiplicity ......................................................... 19 
5.6. 
Other Considerations for Data Analyses and Data Handling 
Conventions ................................................................................................ 20 
6. 
STUDY POPULATION ANALYSES ....................................................................... 21 
6.1. 
Overview of Planned Study Population Analyses ........................................ 21 
6.2. 
Disposition of Subjects ................................................................................ 21 
6.3. 
Demographic and Baseline Characteristics ................................................. 22 
6.4. 
Prior Medical Condition and Disease Characteristics .................................. 22 
6.5. 
Prior and Subsequent Anti-cancer Therapy ................................................ 22 
6.6. 
Concomitant Medications ............................................................................ 23 
7. 
EFFICACY ANALYSES .......................................................................................... 24 
7.1. 
Primary Efficacy Analyses .......................................................................... 24 
7.1.1. 
Endpoint / Variables ..................................................................... 24 
7.1.2. 
Summary Measure ...................................................................... 24 
7.1.3. 
Population of Interest ................................................................... 24 
7.1.4. 
Strategy for Intercurrent (Post-Randomization) Events ................ 24 
7.1.5. 
Statistical Analyses / Methods ..................................................... 24 
7.2. 
Secondary Efficacy Analyses ...................................................................... 30 
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7.2.1. 
Endpoint / Variables ..................................................................... 30 
7.2.2. 
Summary Measure ...................................................................... 35 
7.2.3. 
Population of Interest ................................................................... 36 
7.2.4. 
Statistical Analyses / Methods ..................................................... 36 
7.2.4.1. 
Statistical Methodology Specification .......................... 36 
8. 
SAFETY ANALYSES ............................................................................................. 38 
8.1. 
Extent of Exposure ..................................................................................... 38 
8.2. 
Adverse Events Analyses ........................................................................... 41 
8.3. 
Adverse Events of Special Interest Analyses .............................................. 41 
8.4. 
Deaths and Serious Adverse Events ........................................................... 46 
8.5. 
Adverse Events Leading to Discontinuation of Study Treatment 
and/or Withdrawal from the Study and Other Significant Adverse 
Events ........................................................................................................ 47 
8.6. 
Pregnancies ................................................................................................ 47 
8.7. 
Clinical Laboratory Analyses ....................................................................... 48 
8.8. 
Liver Function Analyses .............................................................................. 49 
8.9. 
Other Safety Analyses ................................................................................ 49 
9. 
PHARMACOKINETIC ANALYSES ......................................................................... 52 
9.1. 
Primary Pharmacokinetic Analyses ............................................................. 52 
9.2. 
Secondary Pharmacokinetic Analyses ........................................................ 52 
9.2.1. 
Endpoint / Variables ..................................................................... 52 
9.2.1.1. 
Drug Concentration Measures .................................... 52 
9.2.1.2. 
Derived Pharmacokinetic Parameters......................... 52 
9.2.2. 
Summary Measure ...................................................................... 52 
9.2.3. 
Population of Interest ................................................................... 53 
9.2.4. 
Strategy for Intercurrent (Post-Randomization) Events ................ 53 
10. SECONDARY ANALYSES ..................................................................................... 53 
10.1. 
Immunogenicity Analyses ........................................................................... 53 
10.2. 
Patient Reported Outcomes ........................................................................ 54 
10.2.1. 
Endpoint / Variables ..................................................................... 54 
10.2.2. 
Population of Interest ................................................................... 54 
10.2.3. 
Statistical Measures ..................................................................... 54 
10.2.3.1. Summary Measure ..................................................... 54 
11. REFERENCES ....................................................................................................... 57 
12. APPENDICES ........................................................................................................ 59 
12.1. 
Appendix 1: Protocol Deviation Management and Definitions for Per 
Protocol Population ..................................................................................... 59 
12.2. 
Appendix 2: Schedule of Activities .............................................................. 60 
12.2.1. 
Protocol Defined Schedule of Events ........................................... 60 
12.3. 
Appendix 3: Assessment Windows ............................................................. 61 
12.4. 
Appendix 4: Study Phases and Treatment Emergent Adverse 
Events ........................................................................................................ 62 
12.4.1. 
Study Phases .............................................................................. 62 
12.4.1.1. Study Phases for Concomitant Medication ................. 62 
12.4.2. 
Treatment Emergent Flag for Adverse Events ............................. 63 
12.5. 
Appendix 5: Data Display Standards & Handling Conventions .................... 64 
12.5.1. 
Reporting Process ....................................................................... 64 
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12.5.2. 
Reporting Standards .................................................................... 64 
12.5.3. 
Reporting Standards for Pharmacokinetic .................................... 65 
12.6. 
Appendix 6: Derived and Transformed Data ............................................... 66 
12.6.1. 
General ........................................................................................ 66 
12.6.2. 
Study Population .......................................................................... 67 
12.6.3. 
Safety .......................................................................................... 68 
12.6.4. 
Patient Reported Outcomes (PRO) .............................................. 68 
12.7. 
Appendix 7: Reporting Standards for Missing Data ..................................... 76 
12.7.1. 
Premature Withdrawals ................................................................ 76 
12.7.2. 
Handling of Missing Data ............................................................. 76 
12.7.2.1. Handling of Missing and Partial Dates ........................ 76 
12.8. 
Appendix 8: Values of Potential Clinical Importance ................................... 79 
12.9. 
Appendix 9: Abbreviations & Trade Marks .................................................. 80 
12.9.1. 
Abbreviations ............................................................................... 80 
12.9.2. 
Trademarks ................................................................................. 81 
12.10. Appendix 10: List of Data Displays.............................................................. 82 
12.10.1. Data Display Numbering .............................................................. 82 
12.10.2. Mock Example Shell Referencing ................................................ 82 
12.10.3. Deliverables ................................................................................. 82 
12.10.4. Study Population Tables .............................................................. 83 
12.10.5. Efficacy Tables ............................................................................ 87 
12.10.6. Efficacy Figures ........................................................................... 91 
12.10.7. Safety Tables ............................................................................... 92 
12.10.8. Safety Figures ............................................................................. 98 
12.10.9. Pharmacokinetic Tables ............................................................... 99 
12.10.10. Pharmacokinetic Figures ........................................................... 100 
12.10.11. Patient Reported Outcomes Tables ........................................... 101 
12.10.12. Patient Reported Outcomes Figures .......................................... 104 
12.10.13. ICH Listings ............................................................................... 105 
12.10.14. Non-ICH Listings ........................................................................ 110 
12.11. Appendix 11: Example Mock Shells for Data Displays .............................. 111 
12.12. Appendix 12: SDAC REPORTING PLAN .................................................. 112 
13. INTRODUCTION .................................................................................................. 113 
13.1. 
References to External Documents........................................................... 113 
13.2. 
OVERVIEW OF ANALYSES SPECIFIED IN THE IDMC CHARTER ......... 113 
13.3. 
GENERAL SDAC REPORTING CONVENTIONS ..................................... 114 
13.3.1. 
Sample Report ........................................................................... 114 
13.3.2. 
Open and Closed Session Reports ............................................ 114 
13.3.3. 
General Analysis Conventions ................................................... 115 
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13.3.4. 
Graphical Conventions ............................................................... 115 
13.3.5. 
P-values .................................................................................... 116 
13.3.6. 
Use of Listings when Data Are Limited ...................................... 116 
13.3.7. 
Considerations for Analysis of Interim Data ............................... 116 
13.4. 
PROPOSED DETAILED TABLE OF CONTENTS ..................................... 117 
13.4.1. 
Accrual and Study Status ........................................................... 117 
13.4.2. 
Baseline Characteristics ............................................................ 117 
13.4.3. 
Adverse Events.......................................................................... 118 
13.4.4. 
Central Laboratory Measures ..................................................... 118 
13.4.5. 
Other Follow-up Measures ......................................................... 119 
13.4.6. 
Efficacy and Interim Analyses .................................................... 119 
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1. 
INTRODUCTION 
The purpose of this reporting and analysis plan (RAP) is to describe the analyses to be 
included in the Clinical Study Report for Protocol: 
Revision Chronology: 
2017N337080_00 
23-JUL-2018 
Original 
2017N337080_01 
20-SEP-2018 
Amendment No.1 Protocol was amended at the request 
of the regulatory authority to provide additional 
clarification and guidance on specific aspects of the 
protocol 
2017N337080_02 
15-JUL-2019 
Amendment No.2 Protocol was amended based on 
regulatory and ethics committee feedback to provide 
additional clarification and guidance on specific aspects 
of the protocol as described in the table in the protocol 
2017N337080_03 
29-OCT-2020 
Amendment No.3 . Protocol was amended to add new 
substudies  
TMF-11698443 
02-FEB-2021 
Amendment No. 4. Protocol was amended to change 
the primary analysis criteria. 
2. 
SUMMARY OF KEY PROTOCOL INFORMATION 
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan 
There were no changes or deviations to the originally planned statistical analysis 
specified in the protocol amendment 4 (Dated: 02/FEB/2021). 
2.2. 
Study Objective(s) and Endpoint(s) 
Part 1: 
Objectives 
Endpoints 
Primary Objectives 
Primary Endpoints 
• 
To determine the safety and 
tolerability of novel regimens 
• 
AEs, SAEs, DLTs, changes in safety/laboratory 
assessment parameters, dose modifications 
Secondary Objectives 
Secondary Endpoints 
• 
To provide a preliminary evaluation 
of the efficacy of feladilimab in 
combination with novel regimens 
• Objective Response Rate (ORR) 
• 
Disease Control Rate (DCR) 
• Characterize the pharmacokinetic 
properties of feladilimab (ICOS 
Agonist) or investigational 
feladilimab combination partners 
• PK parameters that include Cmax and Cmin for 
feladilimab and in combination (and investigational 
agent/s included in other arms), as data permit. 
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Objectives 
Endpoints 
Exploratory Objectives 
Exploratory Endpoints 
 
Part 2: 
Objectives 
Endpoints 
Primary Objectives 
Primary Endpoints 
• 
Determine whether experimental 
regimens provide evidence for 
improved survival over SoC 
therapy 
• 
Overall survival as measured by time from 
randomization to death 
Secondary Objectives 
Secondary Endpoints 
• 
Evaluate milestone survival in 
participants treated with 
experimental regimens versus SoC 
therapy for NSCLC 
• 
Milestone survival rate at 12 and 18 months 
• Evaluate other measures of 
antitumor activity of the 
experimental regimens compared 
      with SoC therapy for NSCLC 
      (RECIST 1.1 and iRECIST)                
• CR, PR, SD, PD, PFS, ORR, DOR, DCR 
        iCR, iPR, iUPD, iCPD, iSD 
        iPFS; iORR; iDOR 
• 
Evaluate the safety and tolerability 
of the experimental regimens 
compared with SoC therapy for 
NSCLC 
• 
Frequency and severity of AEs, AESI; SAEs and 
AE/SAEs leading to dose 
modifications/delays/withdrawals; changes in 
laboratory, vital signs, and safety assessment 
parameters, including immunogenicity (ADA) 
• 
Characterize the pharmacokinetic 
properties of feladilimab /SoC, or 
investigational feladilimab 
combination partners 
• 
PK parameters that may include Cmax and Cmin for 
feladilimab and SoC in combination (and 
investigational agent/s included in other arms) and 
for SoC alone, as data permit.. 
• Determine immunogenicity of 
experimental regimens 
• ADA incidence for feladilimab and combination 
partners (where appropriate) 
Exploratory Objectives 
Exploratory Endpoints 
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Objectives 
Endpoints 
 Note: The prefix “i”,used for response related abbreviations in the above table indicates immune 
responses assigned using iRECIST. 
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2.3. 
Study Design 
Overview of Study Design and Key Features 
 
ICOS: Inducible T-Cell Co-Stimulator; NSCLC: non-small cell lung cancer; PD(L)1: Programmed Cell Death 
Protein 1 or Programmed Cell Death Ligand 1.  
Note: Randomization of participants to experimental treatment regimens/arms may not occur in parallel.  It 
should also be noted that the terms ‘regimen’ and ‘arm’ may be used interchangeably throughout the 
document. 
 
Design 
Features 
• A  randomized, open-label, platform trial utilizing a master protocol  
• The study is structured as a series of substudies that share a common 
control arm 
• The study has 2 parts, i.e. part 1 and part 2. 
• Part 1 is a non-randomized part based on safety and 
pharmacokinetics/pharmacodynamics (PK/PD) evaluation. 
• Part 2 is a randomized, Phase II part comparing the efficacy and safety of 
these novel regimens with SoC. 
• Sub-study 1 has only part 2 and subsequent sub-studies (sub-studies 2,3 
and 4) have both part 1 and 2  
• Additional regimens may be added based on emerging nonclinical and 
clinical data, via future protocol amendment(s). This RAP will be upated as 
new arms are added. 
• The study will evaluate the efficacy of feladilimab (ICOS Agonist) in 
combination with other treatment regimens compared with SoC (docetaxel) 
alone as the standard subsequent line chemotherapy Within Part 2 of each 
sub-study, patients will be randomized to receive either SoC or the 
experimental treatment; the randomisation ratios may change depending on 
the number of sub-studies running in parallel. 
• 
Additional treatment arms may be added as sub-studies via future protocol 
amendments, and ongoing treatment arms may be dropped based on interim 
OS results or emerging safety information 
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Overview of Study Design and Key Features 
Dosing 
 
Sub-
study 
Treatment 
Arm 
Dosage 
Route of 
Administration 
Dosing 
Frequency 
SoC 
Docetaxel 
75 
mg/m2 
IV infusion 
Once Q3W 
Sub-study 
1 
feladilimab 
80 mg 
IV infusion 
Once Q3W 
Docetaxel 
75 
mg/m2 
IV infusion 
Once Q3W 
Sub-study 
2 
Ipilimumab 
1 mg/kg 
 
3 mg/kg 
IV infusion 
Once Q3W 
feladilimab 
24mg 
IV infusion 
Once Q3W 
Sub-study 
3 
Niraparib 
200 mga 
300 mgb 
Oral 
Daily 
feladilimab 
24mg 
IV infusion 
Once Q3W 
Sub-study 
4 
Dostarlimab 
500 mg 
IV infusion 
Once Q3W 
Cobolimab 
300 mg 
IV infusion 
Once Q3W 
feladilimab 
24mg 
IV infusion 
Once Q3W 
a: For participants with a baseline body weight <77 kg or baseline platelet count 
<150,000/μL. 
b: For participants with baseline body weight ≥77 kg and baseline platelet count 
≥150,000/μL. 
 
• 
Experimental treatment (combination) will continue to be administered at 
the indicated schedule with the maximum duration as specified in the 
protocol for each combination arm, or until disease progression as 
determined by iRECIST, death, unacceptable toxicity, or other protocol-
defined criteria are met. 
• Single agent SoC treatment may continue until disease progression, 
death, unacceptable toxicity, withdrawal of consent, or per insitiutional 
standard for docetaxel. 
 
Time & 
Events 
• [Refer to Appendix 2: Schedule of Activities] 
Treatment 
Assignment 
At study start, participants will be randomized 1:2 to Arm 1 (SoC) and Arm 2, i.e., 
33% and 67%, respectively. Between 10-20% of newly enrolled participants in 
subsequent sub-studies (depending upon the number of experimental arms in the 
trial) will be randomized to SoC once the initial 35 participants have been enrolled 
on control. Once determined to be eligible for the study, all participants will be 
centrally randomized using RAMOS, an Interactive Web Response System 
(IWRS). 
Interim 
Analysis 
• No interim analysis is involved in part 1 
• In part 2, interim analyses focusing on safety (also including OS) will be 
performed approximately every 3 to 6 months depending on the amount 
of additional data accrued. These interims would be conducted across all 
substudies, reported by treatment and SoC will be combined across all 
substudies.  
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Overview of Study Design and Key Features 
• 
An interim analysis of OS will be conducted for each experimental arm 
after approximately 45 events (experimental arm and SoC combined) 
and a minimum of 18 events from experimental arm have been 
observed.  
• 
Interim analysis will assess futility.  Success will only be declared at the 
final analysis. 
• 
Interim analysis will be performed by an independent third party 
Statistical Data Analysis Center (SDAC) and details of Interim Analysis 
Plan will not be described in this document but will be described in 
SDAC Reporting Plan (Section 12.12) 
 
2.4. 
Statistical Hypotheses / Statistical Analyses 
2.4.1. 
Hypothesis  
Part 1: The primary objective of Part 1 is to establish the safety and tolerability of the 
experimental combination regimen of each substudy. 
Part 2: 
The primary objective of the study is to determine whether the experimental arms 
prolong overall survival relative to standard of care (SoC).  
The null hypothesis is that there is no difference in overall survival between each 
experimental arm and the SoC and alternative hypothesis is that the experimental regimen 
improves overall survival over the SoC. No comparisons will be made between 
experimental arms.  
The predictive probability inference approach will be used as the basis for both interim 
and final success decision making. The predictive probability of Phase III study success 
(defined as a statistically significant log-rank test with1-sided alpha=0.025) will be 
calculated as a measure of the improvement in OS in the experimental arm compared 
with the SoC arm.  
As this is a signal finding study and not confirmatory, each experimental arm will be 
compared to control in a pairwise fashion with no adjustment for multiple comparisons. 
2.4.2. 
Sample Size 
Part 1: 
A maximum of 15 participants will be enrolled to each scheduled regiment in Part 1.     
Part 2: 
In Part 2, 70 participants in each experimental arm and a minimum of 35 participantes in 
the SoC arm will be randomized. Sample size and associated operating characteristics 
were evaluated via simulation. 
 
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The 8-month milestone survival in the SoC arm is estimated to be ~40% in advanced 
squamous cell lung cancer (Brahmer, 2015), ~60% in advanced non-squamous lung cancer 
(Borghaei, 2015), and ~50% in PD-L1 positive population (Herbst, 2016). The participant 
population in the current study is expected to be a mixed population with both squamous 
and nonsquamous lung cancer participants; therefore, mean target rate is assumed to be 
~50% (Figure 1). 
 
For the target effect of experimental regimens, there is a potential delayed effect at 
treatment start and sustained effect after prolonged follow-up (Brahmer, 2015; Borghaei, 
2015). The survival probability in these arms is expected to overlap that in the SoC arm for 
up to 4 months from start of treatment followed by a separation. It is hypothesized that 
percentage of surviving participants is maintained at 20% after 24 months (Figure 1). 
 
Under the alternative hypothesis, three-piece piecewise Weibull distributions are used to 
describe the survival distribution of each experimental arm and two-piece piecewise 
Weibull distributions are used to describe the survival curve of docetaxel (Table 48 in 
Section 12.13.1 of the protocol describes the simulation parameters ). Using this modelling 
approach for the primary endpoint of OS, the assumed survival curve for the SoC arm is 
presented using blue dashes and the target survival curve for the experimental arm is 
presented as the solid red curve in Figure 1.  Based on these two curves, the hazard ratio is 
approximately 0.58. 
 
Sample size was chosen by simulating the a study in which 4 experimental arms enter the 
master protocol at different points in time. Enrollment of 9 participants per month is 
assumed. Interim and final analyses are performed based on predetermined decision rules 
as specified in Section 3. The planned Phase III sample size is 300 (150 participants per 
arm and a total of 210 events).   The future phase 3 trial will use the log-rank (frequentist) 
test and the decision rule at interim and end of phase 2 will use the (Bayesian) predictive 
probability, given the results in phase 2, that the future log-rank test in phase 3 will be 
significant, thus, resulting in a methodology that is a mixture of Bayesian and frequentist. 
Simulations assess the Operating Characteristics of the predictive probability decision 
criteria under the null and alternative hypotheses. A cutoff of 43% or greater for the 
predictive probability of phase 3 success is used to define success for each experimental 
arm. Sample size was calculated under the simulated survival curves shown below (Figure 
1).  
The final analysis of OS for a substudy will be performed when approximately 85 death 
events have occurred in the experimental arm and SoC arm combined, and the last 
participant in that substudy has been randomized for at least 6 months. In the case death 
events occur at a rate lower than expected due to potentially prolonged survival benefit, to 
avoid substantial delay of final analysis for a substudy, the primary analysis for a substudy 
may be conducted once approximately 75 events have occurred and the last participant in 
that substudy has been randomized for at least 6 months, at the discretion of the Sponsor. 
A minimum of 35 events are needed from the experimental arm for both primary and final 
analysis. 
Assuming the true HR≈0.58, 85 death events will provide 94.2% probability (power) of 
achieving the predictive probability success criteria for future phase 3 success of ≥ 43%. 
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In the case of primary analysis being performed with 75 death events, it will provide 88.3% 
probability of achieving the predictive probability success criteria. If the true HR is 1, 85 
and 75 death events will provide 16.6% and 18.2% probability of achieving the predictive 
probability success criteria (Type I error), respectively 
Figure 1 
Assumed Survival Probability Under Alternative Hypothesis in 
Experimental Regimnes (Red) and Docetaxel (Blue) 
 
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3. 
PLANNED ANALYSES 
3.1. 
Interim Analyses 
Part 1: 
No interim analysis will be performed in part 1 of the study 
Part 2: 
This is a platform study utilizing a master protocol designed so that experimental arms 
may enter and leave the trial independently at different time points as determined by pre-
specified decision criteria. This study will be conducted under the auspices of an IDMC 
and Steering Committee. The IDMC will review all available interim safety and efficacy 
(OS only) data as the study progresses. The details of the data that will be reviewed by 
IDMC is described in the IDMC charter and/or the SDAC Reporting Plan (Section 
12.12). The Steering Committee will provide guidance over key decision points during 
the conduct of the study including, but not limited to, the introduction of new 
experimental arms into the master protocol, graduation of existing arms for further 
development in other studies, and end of study. The SoC may be changed during the 
course of the study and this may require update to the RAP and study protocol.  
Interim analyses will be performed approximately every 3 to 6 months depending on the 
amount of additional data accrued.  
For each experimental arm, an interim analysis of OS will be performed. The study may 
be stopped for futility at this interim analysis.  
3.1.1. 
Interim Analyses for Overall Survival (OS) 
Interim Analysis will be performed by Statistical Data Analysis Center (SDAC) for IDMC. 
OS is defined as the interval from date of randomization to the date of death, irrespective 
of the cause of death.  If a participant does not have a documented date of death or is lost 
to follow-up, time of death will be censored at the date of last contact. 
An interim analysis of OS will be conducted for each experimental arm after approximately 
45 events (experimental arm and SoC combined) and a minimum of 18 events from 
experimental arm have been observed. Interim analyses will not be used to declare success 
of any experimental arm. 
 
The study will employ a Bayesian decision-making framework based on the predictive 
probability of observing a significant improvement in OS in a future Phase III trial.  The 
predictive probability inference approach will be used as the basis for interim analyses. 
The predictive probability of Phase III study success (defined as a statistically significant 
improvement in OS, 1-sided alpha=0.025) will be calculated as a measure of the 
improvement in OS in the experimental arm compared with the SoC arm.  Each 
experimental arm will be compared to the SOC arm in a pairwise fashion with no 
adjustment for multiple comparisons. 
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If the predictive probability of phase 3 success for a particular experimental arm is very 
low (as defined in the IDMC charter and/or SDAC Reporting Plan (Section 12.12), that 
experimental arm may be considered for termination. Final decision on termination of an 
experimental arm will be based on the totality of the data, which will include the calculated 
predictive probability of success and the available safety data for that experimental arm. 
 
3.2. 
Primary and Final Analyses 
The final planned primary analyses for each experimental arm will be performed after the 
completion of the following sequential steps: 
Part 1: 
1. A futility analysis of ORR will be conducted after 10 participants have had at 
least two post baseline RECIST assessments. 
2. All required database cleaning activities have been completed and final database 
release (DBR) and database freeze (DBF) has been declared by Data 
Management. 
3. Randomization codes have been distributed according to RandAll NG. 
 
Part 2: 
1. The final analysis for each experimental arm will occur after observing approximately 
85 events (experimental regimen and SoC combined) with minimum of 35 events in 
the experimental arm. 
2. All required database cleaning activities have been completed and final database 
release (DBR) and database freeze (DBF) has been declared by Data Management. 
3. Randomization codes have been distributed according to RandAll NG. 
The rest of the data on remaining subjects will be reported appropriately at study end. 
The RAP will be updated accordingly for each sub study.  
In the case death events occur at a rate slower than expected due to potentially prolonged 
survival benefit, to avoid substantial delay of final analysis for a substudy, primary 
analysis for a substudy may be conducted once approximately 75 events have occurred 
and at least 35 events observed in the experimental arm, and the last participant in that 
substudy has been randomized for at least 6 months, at the discretion of the Sponsor. 
 
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4. 
ANALYSIS POPULATIONS 
Population 
Definition / Criteria 
Analyses Evaluated 
Screened 
• 
All participants who were screened for eligibility.  
• 
Study Population 
Safety 
• 
All randomized participants who received at least one 
dose of SoC or experimental regimen based on actual 
treatment received. 
 
• 
Safety 
Intent-To-Treat 
(ITT) 
• 
All participants who were randomized to treatment 
regardless of whether the participants actually 
received study treatment. 
• 
Study Population 
• 
Efficacy 
Pharmacokinetic 
(PK) 
• 
All participants in the safety population from whom at 
least one blood sample was obtained and analysed for 
PK concentration.  
• 
PK Concentration 
and PK 
parameters 
DLT Evaluable 
• 
A subset of participants in part 1 who have 
received the first course of treatment containing 
both agents within a sub-study and followed up for 
a 21-day period or withdrawn within 21 days due 
to an AE meeting the definition of a DLT. 
• 
For oral dosing, a participant is considered DLT 
evaluable if they received at least 80% the first 
course of treatment containing both agents within 
a sub-study and followed up for a 21-day period 
or withdrawn within 21 days due to an AE meeting 
the definition of a DLT 
• 
DLT  
Refer to Appendix 10 : List of Data Displays which details the population used for each display. 
4.1. 
Protocol Deviations 
Important and non-important protocol deviations (including deviations related to study 
inclusion/exclusion criteria, conduct of the trial, patient management or patient 
assessment) will be summarised and important protocol deviations will be listed. 
 
Protocol deviations will be tracked by the study team throughout the conduct of the study 
in accordance with the Protocol Deviation Management Plan. 
o Data will be reviewed prior to freezing the database to ensure all important 
deviations are captured and categorised on the protocol deviations dataset.  
o This dataset will be the basis for the summaries and listings of protocol 
deviations. 
A separate listing of all inclusion/exclusion criteria deviations will also be provided. This 
summary will be based on data as recorded on the inclusion/exclusion page of the eCRF. 
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5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA 
HANDLING CONVENTIONS 
5.1. 
Study Treatment & Sub-group Display Descriptors 
Treatment Group Descriptions 
RandAll NG  
Data Displays for Reporting  
Code 
Description 
Description 
Order in TFL  
S 
Standard of Care Docetaxel 75 
mg/m2 
Docetaxel 
1 
A 
GSK3359609 (ICOS Agonist) 
80 mg plus docetaxel 
(Treatment Regimen 1) 
GSK3359609 80 mg 
plus Docetaxel 75 
mg/m2 
2 
E 
GSK3359609 (ICOS Agonist) 
plus 1 mg/kg Ipilimumab 
(Treatment Regimen 2) 
Feladilimab 24 mg plus 
Ipilimumab 1 mg/kg  
2 
F 
GSK3359609 (ICOS Agonist) 
plus 3 mg/kg Ipilimumab 
(Treatment Regimen 3) 
Feladilimab 24 mg plus 
Ipilimumab 3 mg/kg 
3 
G 
GSK3359609 (ICOS Agonist) 
plus Niraparib (Treatment 
Regimen 4) 
Feladilimab 24 mg plus 
Niraparib 
2 
H 
 
GSK3359609 (ICOS Agonist) 
plus Dostarlimab plus 
Cobolimab (Treatment 
Regimen 5) 
Feladilimab 24 mg plus 
Dostarlimab 500 mg 
plus Cobolimab 300 mg 
2 
5.2. 
Baseline Definitions 
• For all endpoints the baseline value will be the latest pre-dose assessment with a non-
missing value, including those from unscheduled visits. For laboratory data, baseline 
will be the latest non-missing pre-dose value from local lab will be used.  
• Unless otherwise stated, if baseline data is missing no derivation will be performed 
and baseline will be set to missing. 
5.3. 
Multicentre Studies 
In this multicentre and multi-country study, enrolment will be presented by country and 
investigative site. All centres will be pooled prior to analysis.  
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Additional displays on specific region may be explored as data warrants. 
 
5.4. 
Examination of Covariates, Other Strata and Subgroups 
Part 1:  
No stratification and subgroup analysis is performed in part 1. 
Part 2: 
5.4.1. 
Covariates and Other Strata 
The list of covariate and strata described below may be used in descriptive summaries 
and statistical analyses, some of which may also be used for subgroup analyses if data 
permits. Additional covariates and other strata of clinical interest may also be considered 
as data warrants. 
Category 
Details 
Strata 
Squamous vs. Non-squamous  
Line of PD(L)1 therapy 1st vs. 2nd 
5.4.2. 
Examination of Subgroups 
Subgroups may be explored as the study progresses. Subgroup analysis may be 
performed if data permits. In addition to the strata listed above, subgroups of interest may 
include Gender and Age.   
Subgroup 
Categories 
Gender 
Male; Female 
Age 
<65; ≥65 
. 
5.5. 
Multiple Comparisons and Multiplicity 
Each experimental arm will be compared to control in a pairwise fashion with no 
adjustment for multiple comparisons. No formal comparisons will be made between 
experimental arms. 
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5.6. 
Other Considerations for Data Analyses and Data Handling 
Conventions 
Other considerations for data analyses and data handling conventions are outlined in the 
appendices: 
Section 
Component 
12.3 
Appendix 3: Assessment Windows 
12.4 
Appendix 4: Study Phases and Treatment Emergent Adverse Events 
12.5 
Appendix 5: Data Display Standards & Handling Conventions 
12.6 
Appendix 6: Derived and Transformed Data 
12.7 
Appendix 7: Reporting Standards for Missing Data 
12.8 
Appendix 8: Values of Potential Clinical Importance 
 
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6. 
STUDY POPULATION ANALYSES 
6.1. 
Overview of Planned Study Population Analyses 
The study population analyses will be based on the ITT, unless otherwise specified. 
 Study population analyses including analyses of subject’s disposition, protocol    
deviations, demographic and baseline characteristics, past and current medical conditions, 
prior and concomitant medications, disease characteristics at initial diagnosis and at 
screening, prior and follow-up anti-cancer therapy, surgical/medical procedures, substance 
use, duration of follow up, will be based on GSK Core and Oncology Data Standards. 
Details of the planned displays are presented in Appendix 10: List of Data Displays. 
6.2. 
Disposition of Subjects  
A summary of the number of subjects in each of the analysis populations described in 
Section 4 will be provided. Number of subjects based on the ITT will be summarized by 
country and site for each cohort.  
 
A summary of subject status and reason for study withdrawal will be provided. This 
display will show the number and percentage of subjects who have completed the study 
or have withdrawn from the study, including primary and secondary (if any) reasons for 
study withdrawal. Reasons for study withdrawal will be presented in the order they are 
displayed in the eCRF (Electronic Case Report Form). Subjects who die for any reason 
during on-treatment period will be considered to have completed the study. 
 
A summary of study treatment status will be provided. This display will show the number 
and percentage of subjects who discontinued study treatment and a summary of the 
primary reasons for discontinuation of study treatment. Reasons for study treatment 
discontinuation will be presented in the order they are displayed in the eCRF.  
A listing of treatment discontinuation will be generated. The listing will include last dose 
date and primary reasons for study treatment discontinuation. 
The number and percentage of subjects who passed screening and entered the study, who 
failed screening and therefore were not entered into the study, and subjects who met 
eligibility criteria but were not needed will be summarized along with the reasons for 
failure will be summarized for those subjects who failed screening.  A subject may have 
more than one reason for screen failure. 
Since screen failures are not assigned to treatment groups, the display has only one 
subject-group column regardless of study design. Also, since screen failures cannot be 
attributed to any of the sub-studies repeat reporting may occur in different sub-
studies/parts. This summary will be based on the Screened population.  
 
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The number of subjects will be summarized by Country, Site ID and Investigator ID. This 
summary must be produced based on the all enrolled population.  The total column, 
summarizing subjects regardless of treatment, should always be included.  Rows should be 
sorted alphabetically by country, then in numerical order by Site ID 
6.3. 
Demographic and Baseline Characteristics  
The demographic characteristics (e.g., age, race, ethnicity, sex, height, and baseline body 
weight) will be listed and summarized. Age, height and weight will be summarized using 
the mean, standard deviation, minimum, median, and maximum. In addition, age will also 
be categorized and summarized by 18-64, 65-74, 75-84, and ≥85. The count and 
percentage will be computed for race, ethnicity and sex.  
A separate summary of age ranges based on the ITT population will be provided. Age will 
be summarized in categories: 18-64, 65-84, and ≥85. Race and racial combinations will 
also be summarized. Listing of Race will also be provided. 
6.4. 
Prior Medical Condition and Disease Characteristics   
Disease history and characteristics (primary tumor type, lesion status, time since initial 
diagnosis, stage at initial diagnosis, time since last progression) will be summarized. 
Indicators (yes/no) for the following, collected at screening, will also be summarized: 
measurable disease, non-target lesions, and metastatic disease. Medical conditions 
present at screening will be listed and will be summarized by past and current. Disease 
history and characteristics, as well as these medical conditions, will be presented in data 
listings.  
A summary of disease burden at baseline will be provided. Information on sites of 
metastatic disease at screening will be summarized.  
Prior cancer related surgeries will be summarized and listed. 
6.5. 
Prior and Subsequent Anti-cancer Therapy 
Anti-cancer therapy will be coded using GSK Drug dictionary version 1.6 or higher. Prior 
anti-cancer therapy will be coded using GSK Drug coding dictionary, then summarized 
by type of therapy and listed. A listing of prior anti-cancer therapy will show the 
relationship between Anatomical Therapeutic Chemical (ATC) Level 1, ingredient, and 
verbatim text; therapies will be classified by type (chemotherapy, immunotherapy, 
hormonal therapy, biologic therapy, radioactive therapy, small molecule targeted 
therapy,surgery and radiotherapy).  
ATC classification Level 1 (Body System) information will be included in the dataset 
created but will not appear on the listing or summary.  
The prior and follow-up anti-cancer therapies will be summarised by ingredient. The 
number and percentage of subjects that received different types of anti-cancer therapies 
((chemotherapy, immunotherapy, hormonal therapy, biologic therapy, radioactive 
therapy, small molecule targeted therapy,surgery and radiotherapy) as prior therapy and 
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follow-up therapy will be summarised separately. A subsequent listing of the type of 
Anti-cancer therapy received will be provided with an indicator variable(Yes/No) for 
Prior and Follow-up anti-cancer therapy and prior radio therapy 
 
6.6. 
Concomitant Medications  
Prior medications will be coded using GSK Drug coding dictionary and summarized. The 
summary of prior medications will show the number and percentage of subjects taking 
prior medications by Ingredient. 
Concomitant medications will be coded using GSK Drug coding dictionary and 
summarized. 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.  
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 “Amoxycillin”. In the summary of 
concomitant medications, the ingredients will be summarized by the base only, using 
CMBASECD and CMBASE.  
Concomitant medications will be summarized separately for medications with onset date 
within the on-therapy period and for medications with onset date within the pre-therapy 
period. Note: In order to be considered a concomitant medication, the concomitant 
medication must have been taken at some point during the on-therapy window.  
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 
treatment will be provided. Supportive listings will also be provided. 
 
 
 
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7. 
EFFICACY ANALYSES 
7.1. 
Primary Efficacy Analyses 
7.1.1. 
Endpoint / Variables 
There is no primary efficacy analysis or endpoint for Part 1.  
The primary efficacy analyses for Part 2 will be based on the ITT population, unless 
otherwise specified and all summaries and data listings will use treatment labels as 
specified in Section 5.1.  
 
Primary endpoint is OS and primary analysis is based on the predictive probability of 
Phase III study success. 
 
Overall Survival (OS) is defined as the time from randomization to the date of death for 
any cause. In the absence of confirmation of death, survival time will be censored at the 
last date the subject is known to be alive (i.e., at their last known alive date from long 
term follow-up). 
The length of OS will be calculated as 
OS = death date or last known alive date – date of randomisation + 1 
Subjects lacking data beyond date of  randomisation will have their survival times 
censored at date of  randomisation. 
7.1.2. 
Summary Measure 
Hazard Ratio for OS will be estimated using the cox proportional hazard model stratified 
by the histology(squamous vs. non-squamous) and line of PD-L1 therapy(1st line vs. 2nd 
line) with treatment arm as the sole explanatory variable. 
 
The distribution of OS for each treatment arm will be estimated using the Kaplan-Meier 
method. The median, 25th and 75th percentiles of OS will be estimated and corresponding 
95% confidence intervals will be estimated using the Brookmeyer-Crowley method 
(Brookmeyer, 1982).  
7.1.3. 
Population of Interest  
The primary efficacy analyses will be based on the ITT population, unless otherwise 
specified. 
7.1.4. 
Strategy for Intercurrent (Post-Randomization) Events 
Not applicable  
7.1.5. 
Statistical Analyses / Methods 
Details of the planned displays are provided in Appendix 10: List of Data Displays and 
will be based on GSK data standards and statistical principles. 
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Unless otherwise specified, endpoints / variables defined in Section 7.1.1 will be 
summarised using descriptive statistics, graphically presented (where appropriate) and 
listed. 
Endpoint / Variables 
• 
OS  
Model Specification 
• 
Hazard ratio for OS and corresponding 95% confidence interval will be estimated 
using the Cox’s proportional hazard model stratified by stratified by the 
histology(squamous vs. non-squamous) and line of PD-L1 therapy(1st line vs. 2nd 
line) with treatment arm as the sole explanatory variable. 
 
• 
The predictive probability of Phase III study success (defined as a statistically 
significant log-rank test with 1-sided alpha=0.025) will be calculated as a measure 
of the improvement in OS in the experimental arm compared with the SoC arm.   
 
• 
The predictive probability of success in a future Phase III study will be calculated 
using the posterior predictive distribution of log(HR in phase 3), given log(HR from 
phase 2), assuming that both the observed log(HR) and prior for mean of log(HR) 
follow normal distributions as outlined below. 
 
• 
Let us assume that the prior of hazard ratio (in logarithm scale) follows normal 
distribution with mean as θ0 and a standard deviation of sqrt(4/n0) 
 
 
 
𝜃~𝑁(𝜃0, 𝑉0) 
 
where V0 ~ 4/n0, n0 = some number that could be interpreted as the number of events in 
a trial where the prior information came from; a small value corresponds to a large 
variance for the prior distribution and thus, the prior is considered non-informative.  
The expression for the variance comes from (Parmar, 1998) if the trial where the prior 
info was obtained has equal sample size allocation between the 2 groups. 
 
• 
The posterior distribution is also normal (Gelman, 2013) and is given by: 
 
 
 
 
𝜃|𝑥 ~ 𝑁(
𝑉0
𝑉𝑝2 + 𝑉0
𝑥+ 
𝑉𝑝2
𝑉𝑝2 + 𝑉0
𝜃0 ,
1
1 𝑉0
⁄
+ 1 𝑉𝑝2
⁄
). 
• 
The posterior predictive distribution, given the observed data in phase 2, is normal 
(Gelman, 2013) and is of the form 
 
𝑦|(𝑋= 𝑥) ~ 𝑁(
𝑉0
𝑉𝑝2 + 𝑉0
𝑥+ 
𝑉𝑝2
𝑉𝑝2 + 𝑉0
𝜃0 ,
1
1 𝑉0
⁄
+ 1 𝑉𝑝2
⁄
+ 𝑉𝑝3) 
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𝑤ℎ𝑒𝑟𝑒 𝑉𝑝3 = 𝑉[log(𝐻𝑅
̂ 𝑝3)] 
 
• 
and 𝑉𝑝3 is assumed to be known.  If the numerator and denominator of the 
expression for the mean is divided by (𝑉0𝑉𝑝2), the posterior predictive distribution 
is of the form 
𝑌|𝑥 ~ 𝑁
(
 
𝑉0
𝑉0𝑉𝑝2
𝑉𝑝2
𝑉0𝑉𝑝2 +
𝑉0
𝑉0𝑉𝑝2
𝑥+ 
𝑉𝑝2
𝑉0𝑉𝑝2
𝑉𝑝2
𝑉0𝑉𝑝2 +
𝑉0
𝑉0𝑉𝑝2
𝜃0 ,
1
1 𝑉0
⁄
+ 1 𝑉𝑝2
⁄
+ 𝑉𝑝3
)
  
• 
and could be expressed as 
𝑌|𝑥 ~ 𝑁(
1
𝑉𝑝2
1
𝑉0 + 1
𝑉𝑝2
𝑥+ 
1
𝑉0
1
𝑉0 + 1
𝑉𝑝2
𝜃0 ,
1
1 𝑉0
⁄
+ 1 𝑉𝑝2
⁄
+ 𝑉𝑝3) 
or equivalently 
𝑌|𝑥 ~ 𝑁(
𝑥
𝑉𝑝2 + 𝜃0 
𝑉0
1
𝑉0 + 1
𝑉𝑝2
,
1
1 𝑉0
⁄
+ 1 𝑉𝑝2
⁄
+ 𝑉𝑝3). 
 
• 
The planned future phase 3 trial will have equal sample size allocation for the 2 
groups and the total number of events in this phase 3 trial is m. We also assume that 
𝑉𝑝3 is known with value given by its estimate from (Parmar, 1998) 
𝑉𝑝3 ≈4
𝑚. 
• 
The predictive posterior distribution, with 𝑉𝑝3 replaced by its estimate, is of the 
form given in protocol Section 10.5.1 and as shown below 
𝑌|𝑥~𝑁(
𝑥
𝑉𝑝2 + 𝜃0 
𝑉0
1
𝑉0 + 1
𝑉𝑝2
,
1
1 𝑉0
⁄
+ 1 𝑉𝑝2
⁄
+ 4
𝑚). 
 
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• 
If we assume that the prior distribution is non-informative such that 𝑉0 is a very 
large number relative to 𝑉𝑝2,then the posterior predictive distribution (Gelman, 
2013) is given could be reduced to 
𝑌|𝑥 ≈ 𝑁(𝑥, 𝑉𝑝2 + 𝑉𝑝3). 
• 
Success in future phase 3 is defined as “observing a statistically significant one-
sided 2.5% alpha-level log-rank test in a trial where sample size allocation in 2 
groups is equal and the total number of events in the trial is m.”  The log-rank test 
statistic in the future phase 3 trial could be expressed as 
𝑍𝑝3 = (log(𝐻𝑅
̂ 𝑝3) ∗ √𝑚
4  ) ≈𝑁(0,1). 
• 
Under the null hypothesis of equality of hazard in phase 3, the one-sided 2.5% 
alpha-level log-rank test is statistically significant if  
𝑍𝑝3 < −1.96   𝑜𝑟 𝑒𝑞𝑢𝑖𝑣𝑎𝑙𝑒𝑛𝑡𝑙𝑦,      𝑦=  log(𝐻𝑅
̂ 𝑝3) < −1.96 ∗√4
𝑚 . 
• 
The probability of phase 3 success given phase 2 data is calculated using the 
predictive distribution of Y given X=x.  This is the area under the posterior 
predictive distribution of Y given X=x in the region 𝑌< −1.96 ∗√4 𝑚
⁄
, by virtue 
of the additional assumption that 𝑉𝑝2 and 𝑉𝑝3 are known.  If Φ(∙) denotes the 
standard normal distribution function (i.e., Φ(−𝑍𝛼) = 𝛼), then the predictive 
probability of phase 3 success, given phase 2 data, is calculated as 
• 
Φ
(
 
 
−1.96∗√4
𝑚−(
𝑥
𝑉𝑝2+ 𝜃0 
𝑉0
1
𝑉0+ 1
𝑉𝑝2
)
√
1
1 𝑉0
⁄
+ 1 𝑉𝑝2
⁄
+ 4
𝑚
)
 
 . 
• 
Assuming Non−informtaitve Prior, i.,e. 𝑉0 is very large [relative to 𝑉𝑝2 
𝑌|𝑥 ~ 𝑁([
𝑉0
𝑉𝑝2 + 𝑉𝑝0
] 𝑥+ [
𝑉2
𝑉2 + 𝑉0
] 𝜃0,  (
1
[1 𝑉0
⁄
]  +  [1 𝑉𝑝2
⁄
]
+  𝑉3)) 
𝑌|𝑥 ~ 𝑁([
𝑉0
𝑉𝑝2 + 𝑉𝑝0
] 𝑥+ [
𝑉2
𝑉2 + 𝑉0
] 𝜃0,  (
1
[1 𝑉0
⁄
]  +  [1 𝑉𝑝2
⁄
]
+  𝑉3)) 
𝒀|𝒙  ≈  𝑵(𝒙 ,  (𝑽𝒑𝟐 +  𝑽𝟑)) 
• 
Therefore, Phase 3 PoS given Phase 2 Data is: 
 
 
 
 
𝑃(𝑌< −1.96√𝑉3   | 𝑥) 
 
1 
0 
0
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• 
This is area under Posterior Predictive Distribution of 
 
 
 
 
𝑌|𝑥  ~  𝑁(𝑥 ,  (𝑉𝑝2 +  𝑉3)) 
• 
Equivalently, this is the area under 𝑁(0,1) to the left of  
 
 
 
 
 
(−1.96√𝑉3) − 𝑥
√𝑉𝑝2 + 𝑉3
 
𝑉[𝑙𝑜𝑔(𝑠𝑎𝑚𝑝𝑙𝑒 𝐻𝑅)] =  (
1
# 𝐸𝑣𝑒𝑛𝑡𝑠 𝑖𝑛 𝐶𝑜𝑛𝑡𝑟𝑜𝑙)  +  (
1
# 𝐸𝑣𝑒𝑛𝑡𝑠 𝑖𝑛 𝑇𝑟𝑒𝑎𝑡𝑚𝑒𝑛𝑡) 
• 
Therefore: 
 
 
 
𝑉𝑝2 = 𝑉[𝑙𝑜𝑔(𝑠𝑎𝑚𝑝𝑙𝑒 𝐻𝑅) 𝑓𝑟𝑜𝑚 𝑝ℎ𝑎𝑠𝑒 2]   ≈ 
1
𝑛𝑐 +   
1
𝑛𝑡 
 
 
             𝑉3 = 𝑉[𝑙𝑜𝑔(𝑠𝑎𝑚𝑝𝑙𝑒 𝐻𝑅) 𝑖𝑛 𝑝ℎ𝑎𝑠𝑒 3]   ≈ 
4
𝑚 
 
 
 
note: m = total # events in a 2-arm study with equal allocation 
• 
At final analysis, PoS is area under 𝑁(0,1) to the left of  
(−1.96√𝑉3 ) − 𝑥
√𝑉𝑝2 +  𝑉3
 
   or equivalently 
(−1.96√4
𝑚 )  −𝑙𝑜𝑔(𝑠𝑎𝑚𝑝𝑙𝑒 𝐻𝑅 𝑓𝑟𝑜𝑚 𝑝𝑙𝑎𝑡𝑓𝑜𝑟𝑚 𝑡𝑟𝑖𝑎𝑙)
√1
𝑛𝑐  +    1
𝑛𝑡  +   4
𝑚
 
 
Model Checking & Diagnostics 
• 
Before using the cox proportional hazard model, the proportional hazards assumption will be 
assessed using the following methods: 
o Kaplan-Meier plot by treatment arm 
o Plot of log(time) against log(-log(survival)) by treatment arm 
o Plot of Schoenfeld residuals for treatment  
o Evaluation of time-dependency of treatment effect by adding an interaction term of 
treatment and time in the Cox model. If the interaction term is significant (p< 0.05), it is 
considered that the proportional hazards assumption is violated. 
• 
If one or more of the tests above demonstrates clear violation of the proportional hazards 
assumption, it is considered the proportional hazards assumption does not hold. Hazard 
ratio and corresponding 95% CI estimated from the Cox model will still be reported.  
 
Model Results Presentation 
• Cox proportional hazard model results will be summarised in tables accounting for the 
stratification factors.  The median, 25th and 75th percentiles of OS will be estimated and 
corresponding 95% confidence intervals will be estimated using the Brookmeyer-Crowley 
method (Brookmeyer, 1982) and presented in tables. In addition Kaplan Mier figures will 
presented to show the distribution of OS. 
Sensitivity and Supportive Analyses 
• If the proportional hazard assumption does not hold, additional analysis based on 
(Restricted Mean Survival Time) RMST may be explored. 
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• Sensitivity analyses will be conducted to evaluate time-dependency in the SoC arm.  The 
exchangeability assumption will be examined by comparing overall survival between non-
concurrent and concurrent SoC data, by using Cox’s proportional hazard model with 
indicator in control data (0: nonconcurrent, 1: concurrent data) as a covariate. If there is a 
difference in OS between non-concurrent and concurrent SoC, this difference will be further 
investigated or examined.  Sensitivity analysis will be conducted if there is evidence of a 
violation of the exchangeability assumption. An example of a sensitivity analysis is one 
where only the concurrent data will be included (i.e., no non-concurrent data are used) in 
evaluating the treatment effect of the experimental regimen at data analysis. 
• A sensitivity analysis may be performed to adjust for the impact of COVID 19. The censoring 
rule as described below will be followed. 
a. Participants will be censored at the earliest date of, 
i. 
Treatment discontinuation related to COVID -19 and not associated with 
disease progression 
ii. 
Death due to COVID-19 infection and not associated with disease under 
study 
b. If none of the above events (i & ii) occurs and an event death occurs, the event will 
be based on the date of death due to any cause other than COVID-19 infection.  
c. Else if both a and b didn’t occur then the participants will be censored at last known 
alive date, as per the primary analysis censoring rules. 
 
 
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7.2. 
Secondary Efficacy Analyses 
7.2.1. 
Endpoint / Variables 
Part 1: 
The secondary efficacy analyses for Part 1 will be based on safety population unless 
otherwise specified. The secondary endpoints in part 1 are, Overall Response Rate (ORR) 
and Disease Control Rate (DCR). 
ORR is defined as the percentage of participants with a best overall confirmed CR or PR 
at any time as per RECIST1.1 
DCR is defined as the percentage of participants with best overall confirmed complete 
response, partial response or stable disease at any time as per RECIST1.1 
Summary measures for ORR and DCR will be provided as mentioned in Section 7.2.3. 
Part 2: 
The secondary efficacy analyses for Part 2 will be based on the ITT population, unless 
otherwise specified and all summaries and data listings will use treatment labels as 
specified in Section 5.1. The key secondary efficacy endpoint is Milestone Survival rate 
at 12 and 18 months. Other secondary endpoints are CR, PR,SD, PD, PFS, ORR, DOR, 
iCR, iPR, iUPD, iCPD, iSD, iPFS, iORR and iDOR which were used to evaluate 
anticancer activity. 
• Milestone Survival rate at 12 months is defined as the percentage of people 
alive until 12 months after randomisation. It is the time from date of 
randomization to the date of death due to any cause during the period of 12 
months. In the absence of confirmation of death during the period of 12 months, 
survival time will be censored at the last contact date. If the death date or date of 
last contact date is after 12 months then the censor date will be randomisation date 
+ 12 months. 
 
• Milestone Survival rate at 18 months is defined as the percentage of people 
alive until 18 months after  randomisation. It is the time from date of 
randomization to the date of death due to any cause during the period of 18 
months. In the absence of confirmation of death during the  period of 18 months, 
survival time will be censored at the last contact date. If the death date or date of 
last contact date is after 18 months then the censor date will be randomisation date 
+ 18 months. 
 
The length of Milestone Survival will be calculated as 
Milestone Survival = death date or last available date (during the period of 12 or 18 
months) – date of randomization + 1 
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Subjects lacking data beyond date of randomisation will have their survival times 
censored at date of  randomisation 
The Milestone Survival Rate will be calculated as the (Kaplan Meir survival 
probabilities at time points 12 months/18 months)  * 100. 
For Anti-cancer activity Analyses, ITT population will be used  unless otherwise 
specified. Anticancer activity will be evaluated based on clinical evidence and response 
criteria. The response data will be summarized by each treatment (iRECIST will be used 
for response endpoints and disease measurements for iORR, iDOR and iPFS; RECIST 
1.1 guidelines will be used for response endpoints and disease measurements for ORR, 
DOR and PFS). 
 
ORR, DCR,  DOR and PFS as well as iORR, iDCR, iDOR and iPFS will be calculated 
and summarized. 
 
ORR or iORR is defined as the percentage of participants with a best overall confirmed 
CR or PR at any time as per RECIST1.1/iRECIST. 
 
DCR or iDCR is defined as the percentage of participants with best overall confirmed 
complete response, partial response or stable disease at any time as per 
RECIST1.1/iRECIST 1.1. 
Best overall response (BOR) or iBOR will be derived on investigator assessments of 
oveall response at each visit recorded from the start of treatment until the criteria for 
progression are met (considering any requirement for confirmation when needed), or the 
date of initiation of new anti-cancer therapy (Note: This excludes palliative radiotherapy), 
or death date, whichever is earliest, as assessed by the investigator per RECIST 1.1 
/iRECIST criteria.  
 
For RECIST 1.1, 
 
To be assigned a status of confirmed CR/PR, a confirmatory disease assessment should be 
performed no less than 4 weeks (28 days) after the criteria for  response are first met.  
 
Responses of CR/PR that do not meet the requirements of confirmed CR/PR are still 
eligible to be considered SD if it has met the SD criteria. 
 
For RECIST 1.1, to be assigned a status of SD, follow-up disease assessment(s) must 
have met the SD criteria at least once after the first dose at a minimum of 8 weeks (56 
days) from baseline. If the minimum of 8 weeks (56 days) for SD is not met, the best 
overall 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 8-
week requirement the best response will be PD. Alternatively, subjects lost to follow-up 
after an SD assessment not meeting the minimum time criteria will be considered not 
evaluable. 
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For iRECIST, confirmatory disease assessment of PR or CR will be performed no less 
than 4 weeks (28 days) after the criteria for response are first met. In addition, a 
confirmatory disease assessment of PD will be performed no less than 4 weeks and up to 
8 weeks later to confirm PD.  
If NE (Not Evaluable) is recorded in between initial and confirmatory (i)CR or (i)PR or 
inbetween iUPD and iCPD then it can disregarded to obtain the Best Response 
A SD in between an intial PR and confirmation PR can also be disregarded to obtain the 
Best Response of PR (see below table) 
An iUPD between initial (i)CR/(i)PR and confirmed (i)CR/(i)PR can also be disregarded, 
as this can be considered to be a pseudo-progression 
Assessment 
1 (overall 
reponse) 
Assessment 
2 (overall 
reponse) 
Assessment 3 (>= 
4 weeks after) 
(overall reponse) 
Assessment 
4 (overall 
reponse) 
Best Response  
(i)CR 
NE 
(i)CR 
- 
(i)CR 
(i)PR 
NE 
(i)PR 
- 
(i)PR 
(i)PR 
SD 
(i)PR 
- 
(i)PR 
(i)CR 
NE 
NE 
(i)CR 
(i)CR 
(i)PR 
NE 
NE 
(i)PR 
(i)PR 
iUPD 
NE 
NE 
iCPD 
iCPD 
(i)CR 
iUPD 
(i)CR 
- 
(i)CR 
(i)PR 
iUPD 
(i)PR 
- 
(i)PR 
(i)PR 
iUPD 
iUPD 
(i)PR 
(i)PR 
 
DOR or iDOR is defined as the time from first documented evidence of CR or PR until 
disease progression or death due to any cause among participants who achieve an overall 
response (i.e., unconfirmed or confirmed CR or PR). Censoring rules will follow those of 
the PFS analysis.  
 
PFS or iPFS defined as time from the date of randomization to the date of disease 
progression per clinical or radiological assessment or death due to any cause, 
whichever occurs earlier. For the analysis of PFS, if the participant received 
subsequent anticancer 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 participant does 
not have a documented date of event, PFS will be censored at the date of the last 
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adequate assessment. 
 
The censoring rules for PFS and DOR are given below in Table 1: 
 
Table 1 
Censoring Rules for PFS and DOR 
Situation 
Date of Event 
(Progression/Death due to 
any cause) or Censored1  
Event (Progression/Death 
due to any cause) 
Or Censored 
Death due to any cause before 
first assessment (or Death at 
baseline or without any 
adequate assessments) 
Date of death 
Event 
No adequate baseline 
assessments and the 
participant has not died due to 
any cause (if the participant 
has died due to any cause 
follow the rules for death 
indicted at the top of the 
table) 
Randomization date 
Censored 
No post-baseline assessments 
and the participant has not 
died due to any cause (if the 
participant has died due to 
any cause follow the rules for 
death due to any cause 
indicated at the top of the 
table) 
Randomization date 
Censored 
No adequate post-baseline 
assessment before start of new 
anticancer therapy 
Randomization date 
Censored 
With post-baseline assessment 
but no progression (or death 
due to any cause)  
Date of last ‘adequate’ 
assessment of response prior to 
any anti-cancer therapy 
Censored 
With adequate post-baseline 
assessment and new 
anticancer treatment started 
(prior to documented disease 
progression)2 or death. 
Date of last ‘adequate’ 
assessment of response (on or 
prior to starting anti-cancer 
therapy)  
Censored 
Death due to any cause or 
progression after missing two 
Date of last ‘adequate’ 
assessment of response3 (prior 
to missed assessments): If the 
disease assessment is every 6 
Censored 
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Situation 
Date of Event 
(Progression/Death due to 
any cause) or Censored1  
Event (Progression/Death 
due to any cause) 
Or Censored 
or more scheduled 
assessments 
weeks, a window of 91 days 
([12=6*2] weeks + 7 day 
window) will be used to 
determine whether there is 
extended time without adequate 
assessment. If the time 
difference between PD/death 
due to any cause and last 
adequate disease assessment is 
more than 91 days, PFS will be 
censored at the last adequate 
disease assessment prior to 
PD/death due to any cause. 
For scans conducted after 49 
weeks, a window of 175 days 
([24=12*2]weeks + 7 day 
window) will be used to 
determine whether there is 
extended time without adequate 
assessment. 
Progression documented4  
Date of assessment of 
progression 
Event5 
Death due to any casue4  
Date of death 
Event 
 
Notes: 
1 Event or censored are based on confirmed responses. 
2 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).  
3  An adequate assessment is defined as an assessment where the response is (i)CR, (i)PR, (i)SD or any 
pseudo-progression (iUPD)  
4 If both progression and Death due to any cause are documented then take the earliest date 
5 If last response is iUPD and participant is still on treatment with no further response evaluation, then the 
participant will be censored at the last iUPD date for iPFS, else the participant will be considred for the 
event. 
 
For iPFS, iRECIST requires the confirmation of progression and uses the terms 
unconfirmed progressive disease (iUPD) and confirmed progressive disease (iCPD). 
 
The progression event date (iPD date) to be used in the calculation of PFS per iRECIST 
should be the first date of documented iUPD provided that iCPD is confirmed at the next 
assessment.  
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If more than one assessment is recorded as iUPD then the final occurrence prior to iCPD 
will be used. The exception to the rule would be when consecutive iUPDs followed by 
iCPD, the first occurrence of iUPDs in a row prior to iCPD will be used. For example, if 
a participant has iUPD at time points 1 and 2 and iCPD at time point 3, then iPD date 
would be the date of time point 1. If iUPD occurs, but is disregarded because of later iSD, 
iPR, or iCR, that iUPD date should not be used as the progression event date. 
If progression is not confirmed and there is no subsequent iSD, iPR, or iCR, then the 
iUPD date will be used as iPD date in the following scenarios: 
• Participant discontinues study intervention because the participant was judged not 
to be clinically stable  
• Participant does not undergo further response assessments due to any reason (i.e., 
participant refusal, protocol non-compliance, or participant death) 
• Next timepoint response of iUPD, and iCPD never occurs 
 
7.2.2. 
Summary Measure 
ORR  
The number and percentage of participants with the BOR in the following response 
categories will be summarized: CR, PR,iCR,iPR. The corresponding exact 95% CI for 
ORR and iORR will also be provided. Participants with unknown or missing responses 
will be treated as non-responders, i.e., these participants will be included in the 
denominator when calculating percentages of response. A figure displaying maximum 
reduction in tumor size and listing of subject level responses will be generated. 
DCR 
The number and percentage of participants with the BOR in the following response 
categories will be summarized: CR, PR, SD, iCR,iPR, iSD. The corresponding exact 95% 
CI for DCR and iDCR will also be provided. Participants with unknown or missing 
responses will be treated as non-responders, i.e., these participants will be included in the 
denominator when calculating percentages of response.  
DOR  
The distribution of DOR will be summarized using the Kaplan-Meier method by 
treatment arm. The median, 25th and 75th percentiles of DOR will be estimated and 
corresponding 95% confidence intervals will be estimated using the Brookmeyer-
Crowley method (Brookmeyer, 1982). Results from this will be descriptively summarised 
in tables and plotted, alogn with subject level listing of DOR. 
 
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PFS  
The distribution of PFS for each treatment arm at will be estimated using the Kaplan-
Meier method. The median, 25th and 75th percentiles of PFS will be estimated and 
corresponding 95% confidence intervals will be estimated using the Brookmeyer-
Crowley method (Brookmeyer, 1982). Results from this will be descriptively summarised 
in tables and plotted, along with subject level listing of PFS. 
Milestone survival rate  
The distribution of Milestone survival rate for each treatment arm at 12 months and 18 
months will be estimated using the Kaplan-Meier method. The median, 25th and 75th 
percentiles of OS will be estimated and corresponding 95% confidence intervals will be 
estimated using the Brookmeyer-Crowley method (Brookmeyer, 1982). Results from this 
will be descriptively summarised in tables and plotted, along with subject level listing of 
milestone survival. 
7.2.3. 
Population of Interest  
The secondary efficacy analyses will be based on the ITT population, unless otherwise 
specified. 
7.2.4. 
Statistical Analyses / Methods 
Details of the planned displays are provided in Appendix 10: List of Data Displays and 
will be based on GSK data standards and statistical principles. 
Unless otherwise specified, endpoints / variables defined in Section 7.2.1 will be 
summarised using descriptive statistics, graphically presented (where appropriate) and 
listed. Key secondary endpoints, such as PFS, DOR and milstone survival rate will be 
analysed (see Section 7.2.4.1). Response rates estimates will be reported with 95% exact 
CI in the summary tables. 
7.2.4.1. 
Statistical Methodology Specification 
Endpoint / Variables 
• 
PFS, DoR 
Model Specification 
• 
Hazard ratio for PFS and DoR and corresponding 95% confidence interval will be estimated 
using the Cox’s proportional hazard model stratified by the randomization factor(s) with 
treatment arm as the sole explanatory variable. 
 
Model Checking & Diagnostics 
The proportional hazards assumption will be assessed using the following methods: 
o Kaplan-Meier plot by treatment arm 
o Plot of log(time) against log(-log(survival)) by treatment arm 
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o Plot of Schoenfeld residuals for treatment  
o Evaluation of time-dependency of treatment effect by adding an interaction term of 
treatment and time in the Cox model. If the interaction term is significant (p< 0.05), it is 
considered that the proportional hazards assumption is violated. 
• 
If one or more of the tests above demonstrates clear violation of the proportional hazards 
assumption, it is considered the proportional hazards assumption does not hold. Hazard 
ratio and corresponding 95% CI estimated from the Cox model will still be reported.  
• 
Additional analysis of PFS and DoR are based on RMST, which does not require the 
proportional hazard assumption may be conducted.  
Text below describes RMST Option 1: Commonly used pre-specified time-point:  
Minimum of last event time in treat and control 
Minimum of last observed time in treat and control 
Time of clinical interest, e.g., 2 yrs.  
SAS macro for calculation is available at: http://bcb.dfci.harvard.edu/~huno/computer-
program/rmst2_ver003.sas   
Text below describes RMST Option 2: The time interval should be between “larger 
than the maximum of smallest event time” and “smaller than the minimum of largest 
follow up time”. R code for calculation is available at: 
http://onlinelibrary.wiley.com/doi/10.1111/biom.12384/abstract 
Model Results Presentation 
Cox proportional hazard model results will be summarised in tables accounting for the 
stratification factors.  The median, 25th and 75th percentiles of PFS/DoR will be estimated 
and corresponding 95% confidence intervals will be estimated using the Brookmeyer-
Crowley method (Brookmeyer, 1982) and presented in tables. In addition Kaplan Mier 
figures will presented to show the distribution of PFS and DoR. 
Sensitivity and Supportive Analyses 
If the proportional hazard assumption does not hold additional analysis based on RMST may 
be explored. 
 
Endpoint / Variables 
• 
ORR and DCR  
Model Specification 
• 
ORR and DCR will be compared between treatment arms using Cochran’s Mantel Haenszel 
test stratified by randomization factors. The exact 95% confidence interval for the difference 
will be calculated.  
 
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8. 
SAFETY ANALYSES 
The safety analyses will be based on the Safety population, unless otherwise specified. 
8.1. 
Extent of Exposure 
Extent of exposure to SOC and experimental arm will be summarized by Number of 
cycles, relative dose intensity and duration of exposure (see Section 12.6.2 for derivation 
details).  
Relative dose intensity (RDI) is the percentage of the actual dose delivered relative to the 
intended dose. Relative dose intensity (RDI) is defined as (Actual cumulative dose 
delivered up to treatment discontinuation)/(Planned cumulative dose up to treatment 
discontinuation)*100. The planned cumulative dose is the total dose that would be 
delivered, if there were no modification to dose or schedule. An RDI of 100% indicates 
that the drug was administered at the dose planned per protocol, without delay or 
reductions. 
 
Treatment compliance is defined as (Actual cumulative dose/Scheduled cumulative 
dose)*100. The scheduled dose accounts for any dose reductions, for example, if a 
participant had a dose reduction from 75 mg/m2 to 60 mg/m2, then the scheduled dose is 
60 mg/m2. 
 Summary statistics will be produced for extent of exposure. 
 
Duration of Exposure in weeks is defined as (treatment stop date – treatment start date + 
1) divided by 7. 
For ITT Population, if subjects were randomized but did not receive any dose they will be 
counted as having zero duration of exposure. Duration of Study treatment will be plotted.  
If the dose was not given at a particular visit , missed doses will be summarised and will 
include: 
• number and percent of subjects with any missed doses. Each subject will 
only be counted once. The percentage will be based on “N”. 
 
• total number of missed doses (events). 
 
• number and percent of subjects with any missed doses by category. 
Number of missed doses will be categorized as 0, 1, 2, 3 or more, and Not 
Evaluable. Not evaluable row is for subjects who did not receive any drug 
in any succeeding time period after the first dose. Each subject will only 
be counted once. The number from each row will add up to N. The 
percentage will be based on “N”.  
• number and percentage of missed doses (events) categorized by the 
reasons for missing a dose.  Subject may be counted in multiple times in 
the same ‘reason’ row if the subject missed the dose multiple times for the 
same reason. Also, note that the same subject may be counted in multiple 
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reason rows, since they could have been missed a dose at different time 
points for different reasons. Therefore, the total number of events counted 
in different reasons must add up to the total number of missed doses (i.e. 
the number in the 2nd section of the table). The percentage will be based 
on the total number of missed doses (events).  
Dose reductions will be summarised by treatment.The summary will include : 
• number and percent of subjects with any reduction. Each subject will only be 
counted once. The percentage will be based on “N”. 
• total number of dose reductions (events). 
• number and percent of subjects with any dose reduction by category. Number of 
dose reductions will be categorized as 0, 1, 2, 3 or more, and Not Evaluable. Not 
evaluable row is for subjects who did not receive any drug in any succeeding time 
period after the first dose. Each subject will only be counted once. The number 
from each row will add up to N. The percentage will be based on “N”.  
• number and percentage of dose reductions (events) categorized by the reasons.  
Subject may be counted in multiple times in the same ‘reason’ row if the subject 
had multiple dose reductions for the same reason. Also, note that the same subject 
may be counted in multiple reason rows, since their doses could have been 
reduced at different time points for different reasons. Therefore, the total number 
of events counted in different reasons must add up to the total number of dose 
reductions (i.e. the number in the 2nd section of the table). The percentage will be 
based on the total number of dose reductions (events).  
   
Dose delays will be summarized by treatment and this will include: 
• number and percent of subjects with any delay. Each subject will only be 
counted once. The percentage will be based on “N”. 
• total number of delays (events). 
• number and percent of subjects with any dose delays by category. Number 
of dose delays will be categorized as 0, 1, 2, 3 or more, and Not Evaluable. 
Not evaluable row is for subjects who did not receive any drug in any 
succeeding time period after the first dose. Each subject will only be 
counted once. The number from each row will add up to N. The 
percentage will be based on “N”. 
• number and percent of dose delays (events) categorized by duration  in 
days (e.g. 1-7, >=8 etc.). The percentages will be based on the total 
number of dose delays (i.e. the number from the 2nd section of the table). 
Subject may be counted in multiple times in the same ‘duration’ row if the 
subject had multiple dose delays for the same duration. Also, note that the 
same subject may be counted in multiple duration rows, since their doses 
could have been delayed at different time points for different lengths of 
time. 
• number and percentage of dose delays (events) categorized by the reasons.  
Subject may be counted in multiple times in the same ‘reason’ row if the 
subject had multiple dose delays for the same reason. Also, note that the 
same subject may be counted in multiple reason rows, since their doses 
could have been delayed at different time points for different reasons. 
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Therefore, the total number of events counted in different reasons must 
add up to the total number of dose delays (i.e. the number in the 2nd 
section of the table). The percentage will be based on the total number of 
dose delays (events).  
Dose delay duration will be calculated as [start date of delayed dose - (start date of 
previous dose + 21)]  
 
If the infusions were stopped early and not completed it will be collected as incomplete 
infusions. Summary of Incomplete Infusion (by treatment) will include: 
 
• number and percent of subjects with any incomplete infusion. Each 
subject will only be counted once. The percentage will be based on “N”. 
• total number of incomplete infusions (events). 
• number and percent of subjects with any incomplete infusion by category. 
Number of incomplete infusion will be categorized as 0, 1, 2, 3 or more.   
Each subject will only be counted once. The number from each row will 
add up to N. The percentage will be based on “N”.  
• number and percentage of incomplete infusions (events) categorized by 
the reasons for stopping an infusion.  Subject may be counted in multiple 
times in the same ‘reason’ row if the subject had incomplete infusion 
multiple times for the same reason. Also, note that the same subject may 
be counted in multiple reason rows, since they could have had incomplete 
infusions at different time points for different reasons. Therefore, the total 
number of events counted in different reasons must add up to the total 
number of incomplete infusions (i.e. the number in the 2nd section of the 
table). The percentage will be based on the total number of incomplete 
infusion (events).  
 
If the infusions were intermittently interrupted but ultimately the infusion was completed 
it will be collected as infusion interruption. Summary of Infusion Interruptions (by 
treatment) will include: 
• number and percent of subjects with any infusion interruptions. Each 
subject will only be counted once. The percentage will be based on “N”.  
• total number of infusion interruptions (events). 
• number and percent of subjects with an infusion interruption by category. 
Number of infusion interruptions will be categorized as 0, 1, 2, 3 or more.  
Each subject will only be counted once. The number from each row will 
add up to N. The percentage will be based on “N”.  
• number and percentage of infusion interruptions (events) categorized by 
the reasons for interruption. Subject may be counted in multiple times in 
the same ‘reason’ row if the subject has infusion interruptions multiple 
times for the same reason. Also, note that the same subject may be 
counted in multiple reason rows, since they could have had infusion 
interruptions at different time points for different reasons. Therefore, the 
total number of events counted in different reasons must add up to the 
total number of infusion interruptions (i.e. the number in the 2nd section of 
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the table). The percentage will be based on the total number of infusion 
interruptions (events).  
 
All dose reductions, infusion interruptions and incomplete infusions, and dose delays will 
be listed separately by treatment. 
8.2. 
Adverse Events Analyses 
Adverse events analyses including the analysis of adverse events (AEs), Serious adverse 
events (SAEs) and other significant AEs will be based on GSK Core Data Standards. 
Details on treatment emergent AEs are provided in Section 12.4.2. Dose modifications, 
dose interruptions, dose reduction dose delays will also be summarized and listed according 
to GSK Oncology Data Standards. The details of the planned displays are provided in 
Appendix 10: List of Data Displays. 
AEs will be coded using the standard MedDRA v.21.1. and grouped by system organ class. 
AEs will be graded by the investigator according to the NCI-CTCAE (version 5.0). 
 
Summary of all Adverse Events and Drug related Adverse events by System Organ Class 
and Preferred Term and Maximum Grade will be reported. Summary of Grade 3-5 AEs 
and drug related Grade 3-5 AEs that occurred in ≥5% of participants will be provided by 
Overall frequency. 
 
A summary of non-serious AEs that occurred in strictly 5% of the participants or above 
will be provided (no rounding for the percentage will be used in terms of 5% threshold, 
e.g. events with 4.9% incidence rate should not be included in this table).  
A summary of number and percentage of participants with any adverse events by maximum 
grade will be produced. AEs will be sorted by PT in descending order of total incidence. 
The summary will use the following algorithms for counting the participant: 
• 
Preferred term row: Participants experiencing the same AE preferred term several 
times with different grades will only be counted once with the maximum grade. 
• 
Any event row: Each participant with at least one adverse event will be counted only 
once at the maximum grade no matter how many events they have. 
• 
Summary of non-serious drug related adverse events by  overall frequency by PT will 
be produced. 
All AEs will be listed. Additionally, a listing of subject IDs for each individual AE will be 
produced. Listing of relationship of adverse event System Organ Class (SOC), Preferred 
term (PT) and verbatim text will be produced. 
AEs with missing date of onset will be considered treatment-emergent. 
8.3. 
Adverse Events of Special Interest Analyses 
A comprehensive list of MedDRA terms based on clinical review will be used to identify 
each type of event. Changes to the MedDRA dictionary may occur between the start of 
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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 details of the 
planned displays are provided in Appendix 10: List of Data Displays. 
AESI are currently defined as events of potential immunologic etiology (irAEs) (however 
this may change over time due to emerging data and analysies). Such events recently 
reported after treatment with other immune modulatory therapy include but not limited 
to: 
 
AE of 
Special 
Interest 
AE of Special 
Interest - Sub 
class  
Preferred Term 
(MedDRA 
Version 21.1) 
System Organ 
Class 
MedDRA 
Code 
The following is the synonyms of AEs of special interest will be combined under the PT 
as shown below.  Note the AE of special interest groups may overlap to each other, 
i.e., one PT may be accounted for multiple AE of special interest groups.  
Potential 
Immune-
Mediated 
Disorders 
Pneumonitis 
Pneumonitis 
Respiratory, 
thoracic and 
mediastinal 
disorders 
10035742 
Dyspnoea 
Respiratory, 
thoracic and 
mediastinal 
disorders 
10013968 
Cough 
Respiratory, 
thoracic and 
mediastinal 
disorders 
10011224 
Dyspnoea 
exertional 
Respiratory, 
thoracic and 
mediastinal 
disorders 
10013971 
Rales 
Respiratory, 
thoracic and 
mediastinal 
disorders 
10037833 
Upper-airway 
cough syndrome 
Respiratory, 
thoracic and 
mediastinal 
disorders 
10070488 
Wheezing 
Respiratory, 
thoracic and 
mediastinal 
disorders 
10047924 
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AE of 
Special 
Interest 
AE of Special 
Interest - Sub 
class  
Preferred Term 
(MedDRA 
Version 21.1) 
System Organ 
Class 
MedDRA 
Code 
Pneumonia 
Infections and 
infestations 
10035664 
Pneumothorax 
Respiratory, 
thoracic and 
mediastinal 
disorders 
10035759 
Respiratory distress 
Respiratory, 
thoracic and 
mediastinal 
disorders 
10038687 
Hypoxia 
Respiratory, 
thoracic and 
mediastinal 
disorders 
10021143 
Myocarditis 
Myocarditis 
 
 
Troponin Increased 
 
 
Cardiac Ischemia  
 
 
Myocardial 
Infarction 
 
 
Colitis 
Colitis 
Gastrointestinal 
disorders 
10009887 
Diarrhea 
Gastrointestinal 
disorders 
10012735 
Hepatitis 
Alanine 
aminotransferase 
increased 
Investigations 
10001551 
Aspartate 
aminotransferase 
increased 
Investigations 
10003481 
Blood alkaline 
phosphatase 
increased 
Investigations 
10059570 
Blood bilirubin 
increased 
Investigations 
10005364 
Hepatocellular 
injury 
Hepatobiliary 
disorders 
10019837 
Immnue-mediated 
hepatitis 
Hepatobiliary 
disorders 
10078962 
Hepatitis 
Hepatobiliary 
disorders 
10019717 
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AE of 
Special 
Interest 
AE of Special 
Interest - Sub 
class  
Preferred Term 
(MedDRA 
Version 21.1) 
System Organ 
Class 
MedDRA 
Code 
Hepatic function 
abnormal 
Hepatobiliary 
disorders 
10019670 
Transaminases 
increased 
Investigations 
10054889 
Gamma-
glutamyltransferase 
increased 
Investigations 
10017693 
Endocrinopathies Hypophysitis 
Endocrine 
disorders 
10062767 
Hypopituitarism 
Endocrine 
disorders 
10021067 
Hypothyroidism 
Endocrine 
disorders 
10021114 
Hyperthyroidism 
Endocrine 
disorders 
10020850 
Hyperglycaemia 
Metabolic and 
nutrition 
disorders 
10020635 
Nephritis and 
Renal Function 
Renal impairment 
Renal and 
urinary disorders 
10062237 
Acute kidney injury 
Renal and 
urinary disorders 
10069339 
Blood creatinine 
increased 
Investigations 
10005483 
Proteinurea 
Renal and 
urinary disorders 
10037032 
Nephritis 
Renal and 
urinary disorders 
10029117 
Pyelonephritis 
acute 
Infections and 
infestations 
10037597 
Urinary retention 
Renal and 
urinary disorders 
10046555 
Uninary 
incontinence 
Renal and 
urinary disorders 
10046543 
Micturition urgency 
Renal and 
urinary disorders 
10027566 
Skin Adverse 
Reactions 
Rash 
Skin and 
subcutaneous 
tissue disorders 
10037844 
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AE of 
Special 
Interest 
AE of Special 
Interest - Sub 
class  
Preferred Term 
(MedDRA 
Version 21.1) 
System Organ 
Class 
MedDRA 
Code 
Rash maculo-
papular 
Skin and 
subcutaneous 
tissue disorders 
10037868 
Rash Papular 
Skin and 
subcutaneous 
tissue disorders 
10037876 
Pruritus 
Skin and 
subcutaneous 
tissue disorders 
10037087 
Erythema 
Skin and 
subcutaneous 
tissue disorders 
10015150 
Dermatitis 
Skin and 
subcutaneous 
tissue disorders 
10012431 
Palmar-plantar 
erythrodysaesthesia 
syndrome 
Skin and 
subcutaneous 
tissue disorders 
10033553 
Skin infection 
Infections and 
infestations 
10040872 
Skin ulcer 
Skin and 
subcutaneous 
tissue disorders 
10040943 
Urticaria 
Skin and 
subcutaneous 
tissue disorders 
10046735 
Vulvovaginal 
pruritus 
Reproductive 
system and 
breast disorders 
10056530 
Cellulitis 
Infections and 
infestations 
10007882 
Eye Pruritus 
Eye disorders 
10052140 
Skin fissures 
Skin and 
subcutaneous 
tissue disorders 
10040849 
Other Immune-
Mediated 
Adverse Events 
Pancreatitis 
Gastrointestinal 
disorders 
10033645 
Lipase increased 
Investigations 
10024574 
Amylase increased 
Investigations 
10002016 
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AE of 
Special 
Interest 
AE of Special 
Interest - Sub 
class  
Preferred Term 
(MedDRA 
Version 21.1) 
System Organ 
Class 
MedDRA 
Code 
Arthritis 
Musculoskeletal 
and connective 
tissue disorders 
10003246 
Infusion-
Related 
Reactions 
Chills 
General 
disorders and 
administration 
site conditions 
10008531 
Wheezing 
Respiratory, 
thoracic and 
mediastinal 
disorders 
10047924 
Pruritus 
Skin and 
subcutaneous 
tissue disorders 
10037087 
Flushing 
Vascular 
disorders 
10016825 
Rash 
Skin and 
subcutaneous 
tissue disorders 
10037844 
Hypotension 
Vascular 
disorders 
10021097 
Infusion related 
reaction 
Injury, poisoning 
and procedural 
complications 
10051792 
Orthostatic 
hypotension 
Vascular 
disorders 
10031127 
 
Summaries of the number and percentage of subjects with AESI will be provided for each 
type of event separately by preferred term and maximum grade. 
Summary of Onset and Duration of the First Occurrence of AESI will also be produced. 
8.4. 
Deaths and Serious Adverse Events 
All deaths will be summarised based on the number and percentage of participants. This 
summary will classify participants by time of death relative to the last dose of medication 
(>30 days or 30 days) and primary cause of death (disease under study, SAE related to 
study treatment, or other). A supportive listing will be generated to provide participant-
specific details on participants who died.  
All SAEs will be tabulated based on the number and percentage of participants who 
experienced the event. The summary table will be displayed in descending order of total 
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incidence by SOC and PT.Summary of Drug related SAE, fatal SAE, drug-related fatal 
SAE will also be produced 
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.  
A listing of reasons for considering an SAE will be provided. 
8.5. 
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 
participant level details for those participants: 
• 
AEs Leading to Discontinuation of Study Treatment  
• 
AEs Leading to Withdrawal from the Study 
• 
AEs Leading to Dose Interruptions 
• 
AEs Leadings to Dose Reductions 
•       AEs Leading to Missed Doses 
An AE leading to dose modification is an AE for which the action with respect to dosing 
is recorded as reduction or interruption of dose. AEs that lead to both a dose modification 
and a discontinuation of study treatment will only appear in the AEs leading to 
discontinuation of study treatment summary.  
8.6. 
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 subjects become pregnant while on the study, the 
information will be included in the narratives and no separate table or listing will be 
produced. 
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8.7. 
Clinical Laboratory Analyses 
Laboratory grades will be reported using the Common Terminology Criteria for Adverse 
Events (CTCAE v5.0). The assessment of laboratory toxicities will examine the 
following laboratory tests performed by local laboratories:  
Laboratory Assessments 
Parameters 
Hematology 
RBC Indices 
WBC count with Differential 
Platelets 
Hemoglobin 
Neutrophils 
 
Hematocrit 
Lymphocytes 
 
RBC count 
Monocytes 
 
 
Eosinophils 
 
 
Basophils 
 
Clinical Chemistry 
 
BUNa 
Potassium 
Bilirubin 
AST (SGOT) 
Creatinineb 
Sodium 
Total protein 
ALT (SGPT) 
Glucose 
Calcium 
Albumin 
Alkaline phosphatase 
LDH 
 
 
 
Coagulation 
INR or PT 
PTT/aPTT 
Cardiac Function 
Troponin I or Troponin T 
Thyroid Function 
Thyroid stimulating hormone 
Free T4 
Free T3 (when clinically indicated) 
Routine Urinalysis 
Specific gravity 
pH, glucose, protein, blood and ketones by dipstick (Note: routine urinalysis by 
method other than dipstick is acceptable, in accordance with local practice).  
Other Screening Tests 
Hepatitis B surface antigen (HBsAg) 
Hepatitis C (Hep C antibody)c 
Serum -hCG Pregnancy test (for women of child bearing potential) 
Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; -hCG = beta-human chorionic 
gonadotropin; BUN = blood urea nitrogen; HBsAg = Hepatitis B surface antigen; RBC = red blood cells; SGOT = serum 
glutamic oxaloacetic transaminase; SGPT = serum glutamic pyruvic transaminase; T3 = triiodothyronine; T4 = 
thyroxine; WBC = white blood cells; INR = International Normalized Ratio; PT = Prothrombin Time; aPTT = Activated 
Partial Thromboplastin Time 
a. 
Required if local laboratory testing is available 
b. 
Creatinine clearance is also required to be calculated using the formula provided in Appendix 9 of the protocol. 
c. 
Participants with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory 
negative Hepatitis C RNA test is obtained.  Hepatitis C RNA Test is optional with negative Hepatitis C antibody 
test. 
d. 
Coagulation factors (PT/INR and aPTT/PTT) should be tested as part of the screening procedures for all 
participants. Any participant receiving anticoagulant therapy should have coagulation factors monitored closely 
throughout the study 
 
 
Change from baseline by scheduled visits will be summarised using mean, median, 
standard deviation, minimum, and maximum. 
 
Summaries of worst case grade increase from baseline grade will be provided for all the 
lab tests that are gradable by CTCAE v5.0. These summaries will display the number and 
percentage of participants with a maximum post-baseline grade increasing from their 
baseline grade. Any increase in grade from baseline will be summarized along with any 
increase to a maximum grade of 3 and any increase to a maximum grade of 4. Missing 
baseline grade will be assumed as grade 0. In addition, the summary will include grade 
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increase from baseline by scheduled visits. For laboratory tests that are graded for both 
low and high values, summaries will be done separately and labelled bi-direction, e.g. 
sodium will be summarized as hyponatremia and hypernatremia.  
For lab tests that are not gradable by CTCAE v5.0, 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 at each  
scheduled visit as well as for the worst case post-baseline. . If a participant has a “Decrease  
to low” and an “Increase to high” during the same time interval, then the participant is  
counted in both the “Decrease to Low” category and the “Increase to High” category. In  
addition, the summary will include worst case changes from baseline with respect to  
normal range by scheduled visits. 
 
Separate summary tables for hematology and chemistry laboratory tests will be produced. 
 
Listing of Laboratory values of Potential Clinical Importance and listing of all laboratory 
values for any value of potential clinical importance will be produced 
 
A separate listing of laboratory data with character values will also be provided. Unless 
otherwise specified, the denominator in percentage calculation at each scheduled visit will 
be based on the number of participants with non-missing value at each visit.   
 
Urinalysis Results will be summarised. Worst-case Urinalysis Results Post-Baseline 
Relative to Baseline will be summarised 
 
A character lab value starting with ‘<X’ or ‘>X’ will be displayed in listings but will not 
be imputed with a numeric value thus will not be included for summaries. 
 
8.8. 
Liver Function Analyses  
Summaries of hepatobiliary laboratory abnormalities will be produced 
 
Possible Hy’s law cases are defined as any elevated (ALT ≥3×ULN and overall 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 subjects receiving 
anticoagulants.  
 
8.9. 
Other Safety Analyses 
The analyses of non-laboratory safety test results including vital signs will be based on 
GSK Core Data Standards, unless otherwise specified. The details of the planned displays 
are presented in Appendix 10: List of Data Displays. 
Unless otherwise specified, the denominator in percentage calculation at each scheduled 
visit will be based on the number of subjects with non-missing value at each particular 
visit. 
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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 supporting listing will also be provided.  
Vital Signs 
 
The following summaries will be provided for vital signs data: 
• Summary of Changes in Heart Rate from Baseline 
• Summary of Increases in Blood Pressure from Baseline 
• Summary of Changes in Temperature from Baseline 
The following listing will also be produced 
• Listing of Vital Signs with Values of Potential Clinical Importance 
The oncology standard categories for Heart Rate in bpm is: 
• Heart Rate in bpm: ‘Decrease to <60’, ‘Increase to >100’   
The oncology standard categories for Systolic Blood Pressure in mmHg are: 
• ‘Any Grade Increase’ 
• ‘Increase to Grade 2 (140-159)’  
• ‘Increase to Grade 3 (>=160)’ 
Note: ‘Any Grade Increase’ will be footnoted as Grade 0 (<120), Grade 1 
(120-139), Grade 2 (140-159), Grade 3 (>=160). 
The oncology standard categories for Diastolic Blood Pressure in mmHg are: 
• ‘Any Grade Increase’ 
• ‘Increase to Grade 2 (90-99)’  
• ‘Increase to Grade 3 (>=100)’ 
Note: ‘Any Grade Increase’ will be footnoted as Grade 0 (<80), Grade 1 
(80-89), Grade 2 (90-99), Grade 3 (>=100). 
The oncology standard category ‘Decrease to < 90’ will be used for the Summary of 
decreases in Systolic Blood Pressure from Baseline. 
 
The oncology standard categories of clinical concern for Temperature are: 
• Temperature in C: ‘Decrease to <=35’, ‘Increase to >= 38’ 
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COVID-19 Assessments 
Confirmed, probable and suspected COVID 19 cases will be summarized and listed. 
Visits impacted by COVID-19 Pandemic will be summarized. Number of subjects with 
missed visits, site visits with one or more assessment missed, remote visit with no 
assessments missed and remote visit with one or more assessments missed will be 
summarized with primary reason for the impact.  
Dose Limiting Toxicity 
For part 1 of the study, a listing of adverse events recorded as dose-limiting toxicities 
during the determinative period will be provided. Additionally, a summary of the number 
of patients experiencing DLTs will be provided. 
 
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9. 
PHARMACOKINETIC ANALYSES 
9.1. 
Primary Pharmacokinetic Analyses 
There are no primary pharmacokinetic analyses for this study. 
9.2. 
Secondary Pharmacokinetic Analyses 
9.2.1. 
Endpoint / Variables 
9.2.1.1. 
Drug Concentration Measures 
Details are included in  Appendix 5: Data Display Standards & Handling Conventions 
(Section 12.5.3 Reporting Standards for Pharmacokinetic) 
9.2.1.2. 
Derived Pharmacokinetic Parameters 
Pharmacokinetic parameters for GSK3359609 and Docetaxel will be calculated by 
standard non-compartmental analysis according to current working practices and using 
the currently supported version of Phoenix WinNonlin.  
All calculations of non-compartmental parameters will be based on actual sampling 
times. Pharmacokinetic parameters listed will be determined from the GSK3359609 and 
Docetaxel concentration-time data, as data permits. 
In addition to non-compartmental PK analysis, a preliminary population PK model 
developed from Phase I study 204691 may also be used to overlay observations from this 
study on PK model predictions (visual predictive check plots), and covariates may be 
explored to understand the variability in Cmax and Cmin parameters. To further support 
interpretation of PK data collected on 205801, PK information may be pooled with data 
from other trials and indications, including the phase I first-time-in-human (FTIH) study 
to develop and evaluate a basic structural PK model. This may be reported separately.  
Parameter 
Parameter Description 
AUC(0-t) 
Area under the concentration-time curve from time 0 to the time of last quantifiable 
concentration will be calculated using the linear trapezoidal rule for each incremental 
trapezoid and the log trapezoidal rule for each decremental trapezoid. 
Cmax 
Maximum observed plasma concentration, determined directly from the concentration-time 
data. 
Cmin 
Minimum observed concentration 
Ctau 
Pre-dose (trough) drug concentration, where tau is the end of the dosing interval 
NOTES: 
• 
Additional parameters may be included as required. 
 
9.2.2. 
Summary Measure 
Plasma Concentration data will be summarised separately for GSK3359609 and 
Docetaxel. Corresponding listing of the plasma concentration values will also be 
produced. Individual plasma concentration-time plots by subject, mean concentration-
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time plots and median concentration time plots will be produced for GSK3359609 and 
Docetaxel separately. 
For each of these parameters for GSK3359609 and Docetaxel separately, the following 
summary statistics will be calculated for each treatment and presented separately: 
median, minimum, maximum, arithmetic mean, 95% confidence interval for the 
arithmetic mean, standard deviation, coefficient of variation (%CV = 100*(sqrt (exp(SD2) 
- 1))) [NOTE: SD = SD of natural log (loge) transformed data]), geometric mean, 95% 
confidence interval for the geometric mean and standard deviation of natural 
logarithmically transformed data. 
 
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. 
All derived PK parameters will be listed. 
9.2.3. 
Population of Interest  
The secondary pharmacokinetic analyses will be based on the Pharmacokinetic 
population, unless otherwise specified. 
9.2.4. 
Strategy for Intercurrent (Post-Randomization) Events 
Not Applicable 
10. 
SECONDARY ANALYSES 
10.1. 
Immunogenicity Analyses 
Serum samples will be collected and tested for the presence of antibodies that bind to 
GSK3359609 (ICOS agonist). These samples may also be tested for presence of 
antibodies that bind to Chinese Hamster Ovary (CHO) host cell proteins such as 
phospholipase B- like (PLBL2). 
 
The actual date and time of each blood sample collection will be recorded. Details of 
blood sample collection (including volume to be collected), processing, storage, and 
shipping procedures are provided in the SRM. 
 
Immunogenicity testing will occur in dosed subjects then analyzed, summarized 
descriptively and/or presented graphically. 
Immunogenicity information will be listed by subject and a summary of the number of 
subjects that are negative and positive for the presence of the antibodies will be provided 
at each timepoint and overall for the subject.  Drug tolerance of the assays will be taken 
into account in categorizing results at each timepoint as positive, negative, or inconclusive.  
A positive result at any timepoint means that the subject’s overall category is positive. 
 
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10.2. 
Patient Reported Outcomes  
Patient reported outcomes will be summarized in part 2 of the study. 
10.2.1. 
Endpoint / Variables 
10.2.2. 
Population of Interest  
The PRO analyses will be based on the ITT population, unless otherwise specified. 
10.2.3. 
Statistical Measures 
10.2.3.1. 
Summary Measure 
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11. 
REFERENCES 
Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al. Nivolumab 
versus docetaxel in advanced nonsquamous non–small-cell lung cancer. New England 
Journal of Medicine. 2015;373(17):1627-39.  
Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, et al. 
Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N 
Engl J Med. 2015; 373:123-35. 
Brookmeyer R, Crowley J. A confidence interval for the median survival time. 
Biometrics, 1982; 38:29-41. 
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New 
response evaluation criteria in solid tumours: revised RECIST guidelines (version 1.1). 
Eur J Cancer. 2009; 45:228-47. 
Gelman A, Carlin J, Stern H, et al. Bayesian Data Analysis. Third Edition. Boca Raton: 
CRC Press; 2013, page 41. 
GlaxoSmiteKline Document Number  2017N337080_02: A Phase II, Randomized, Open-
label Platform Trial Utilizing a Master Protocol to Study Novel Regimens Versus 
Standard of Care Treatment in NSCLC Participants. 
Herbst RS, Baas P, Kim D-W, Felip E, Perez-Gracia JL, Han J-Y, et al. Pembrolizumab 
versus docetaxel for previously treated, PD-L1-positive, advanced non-small cell lung 
cancer (KEYNOTE-010): a randomised controlled trial. The Lancet. 
2016;387(10027):1540-50. 
Parmar M, Torri V, Stewart L. Extracting Summary Statistics to Perform Meta-Analysis 
of the Published Literature for Survival Endpoints. Statistics in Medicine. 1998; 17:2815-
2834. 
Seymour L, Bogaerts J, Perrone A, Ford R, Schwartz LH, Mandrekar S et al. iRECIST: 
guidelines for response criteria for use in trials testing immunotherapeutics. The Lancet 
Oncology. 2017 Mar 1;18(3):e143-e152. https://doi.org/10.1016/S1470-2045(17)30074-8 
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Zhao L, Claggett B, Tian L, et al. On the restricted mean survival time curve in survival 
analysis. Biometrics. 2016; 72:215-221.Appendices 
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12. 
APPENDICES 
12.1. 
Appendix 1: Protocol Deviation Management and Definitions 
for Per Protocol Population 
There is no planned per protocol analysis for this study. 
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12.2. 
Appendix 2: Schedule of Activities 
12.2.1. 
Protocol Defined Schedule of Events 
The Schedules of Activities can be found in the corresponding substudy appendix in 
Section 12.1 
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12.3. 
Appendix 3: Assessment Windows 
The visit assigned to the assessment as entered in the CRF (nominal visit) will be used for 
reporting. 
 
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12.4. 
Appendix 4: Study Phases and Treatment Emergent 
Adverse Events 
12.4.1. 
Study Phases 
Adverse events, serious adverse events, death and other safety domains will be assigned 
to the study phases defined below. Partial dates will be imputed into full dates, if 
applicable, for slotting data to the appropriate categories below. Flag variables (time in 
relation to study phase) indicating the study time periods will be added to the ADaM 
variable APHASE, and the treatment emergent AE flag will be created to ADAE variable 
TRTEMFL.  
Assessments and events will be classified according to the time of occurrence relative to 
Study Treatment Start Date. 
Study Phase 
Definition 
Pre-Treatment  Date < Study Treatment Start Date  
On-Treatment  Study Treatment Start Date ≤ Date ≤ Study Treatment Stop Date + 30 
days  
Post-
Treatment  
Date > Study Treatment Stop Date + 30 days  
 
For parameters where time is not collected, Day 1 assessments are assumed to be taken 
prior to first dose and used as baseline.  
Study Phase 
Definition 
Pre-Treatment  Date < Study Treatment Start Date  
On-Treatment  Study Treatment Start Date ≤ Date ≤ Study Treatment Stop Date  
Post-
Treatment  
Date > Study Treatment Stop Date 
 
12.4.1.1. 
Study Phases for Concomitant Medication 
Study Phase 
Definition 
Prior 
If medication end date is not missing and is before 28 days prior to study treatment 
start date  
Concomitant 
Any medication that is not a prior 
NOTES:  
• 
Please refer to Appendix 7: Reporting Standards for Missing Data for handling of missing and partial 
dates for concomitant medication. Use the rules in this table if concomitant medication date is 
completely missing. 
 
 
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12.4.2. 
Treatment Emergent Flag for Adverse Events 
Flag 
Definition 
Treatment 
Emergent 
Non-serious AEs 
In general, all AEs with a start date after treatment are considered 
emergent regardless of AE start date is before or after treatment stop 
date.  
• 
If AE onset date is on or after treatment start date & on or before treatment stop 
date + 30 days  
o Study Treatment Start Date ≤ AE Start Date ≤ Study Treatment Stop Date 
+ 30 days 
o AE Start Date is missing 
Serious AE/AESI 
o If AE onset date is on or after treatment start date & on or before treatment 
stop date + 30 days Study Treatment Start Date ≤ AE Start Date ≤ Study 
Treatment Stop Date + 30 days 
o AE Start Date is missing 
Missing AE Start Date will be imputed following rules in Section 12.7.2.1 for 
determining Treatment Emergent AEs. 
NOTES:  
• 
[If the study treatment stop date is missing, then the AE will be considered to be On-Treatment.] 
• 
If the study treatment stop date is missing, then the AE will be On-Treatment. 
• 
Time of study treatment dosing and start[/stop] time of AEs should be considered, if collected. 
 
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12.5. 
Appendix 5: Data Display Standards & Handling 
Conventions 
12.5.1. 
Reporting Process 
Software 
• 
The currently supported versions of SAS software will be used. 
Reporting Area 
HARP Server 
: US1SALX00259 
HARP Compound 
: Compound: GSK3359609, study: mid205801  
Each IDMC interim and SAC relevant to eah substudy will be reported under 
mid205801 with a unique reporting effort.  
Analysis Datasets  
• 
Analysis datasets will be created according to SDTM IG Version 3.2 & ADaM IG Version 1.1. 
Generation of RTF Files 
• 
RTF files will  be generated for final SAC per substudy 
12.5.2. 
Reporting Standards 
General 
• 
The current GSK Integrated Data Standards Library (IDSL) will be applied for reporting, unless 
otherwise stated (IDSL Standards Location: 
https://spope.gsk.com/sites/IDSLLibrary/SitePages/Home.aspx): 
• 
4.03 to 4.23: General Principles 
• 
5.01 to 5.08: Principles Related to Data Listings 
• 
6.01 to 6.11: Principles Related to Summary Tables 
• 
7.01 to 7.13: Principles Related to Graphics  
• 
Do not include subject level listings in the main body of the GSK Clinical Study Report. All subject 
level listings should be located in the modular appendices as ICH or non-ICH listings 
• 
All data displays (Tables, Figures & Listings) will use the term “Subject” which reflects CDISC and 
GSK Data Display Standards terminology 
Formats 
• 
GSK IDSL Statistical Principles (5.03 & 6.06.3) for decimal places (DP’s) will be adopted for 
reporting of data based on the raw data collected, unless otherwise stated. 
• 
Numeric data will be reported at the precision collected on the eCRF. 
• 
The reported precision from non eCRF sources will follow the IDSL statistical principles but may be 
adjusted to a clinically interpretable number of DP’s. 
Planned and Actual Time 
• 
Reporting for tables, figures and formal statistical analyses: 
o Planned time relative to dosing will be used in figures, summaries, statistical analyses and 
calculation of any derived parameters, unless otherwise stated. 
o The impact of any major deviation from the planned assessment times and/or scheduled visit 
days on the analyses and interpretation of the results will be assessed as appropriate. 
• 
Reporting for Data Listings:  
o Planned and actual time relative to study drug dosing will be shown in listings (Refer to IDSL 
Statistical Principle 5.05.1). 
o Unscheduled or unplanned readings will be presented within the subject’s listings.  
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Unscheduled Visits 
• 
All unscheduled visits will be included in listings.  
• 
Unscheduled visits will not be included in summary tables and/or figures, except for worst case 
summary tables and/or figures.  
 
Descriptive Summary Statistics 
Continuous Data 
Refer to IDSL Statistical Principle 6.06.1 
Categorical Data 
N, n, frequency, % 
Graphical Displays 
• 
Refer to IDSL Statistical Principals 7.01 to 7.13. 
12.5.3. 
Reporting Standards for Pharmacokinetic 
Pharmacokinetic Concentration Data 
PC Windows Non-
Linear (WNL) File 
PC WNL file (CSV format) for the non compartmental analysis by Clinical 
Pharmacology Modelling and Simulation function will be created  
Note: Concentration values will be imputed as per GUI_51487 
Descriptive 
Summary Statistics, 
Graphical Displays 
and Listings 
Refer to IDSL PK Display Standards. 
Refer to IDSL Statistical Principle 6.06.1. 
Note: Concentration values will be imputed as per GUI_51487 for descriptive 
summary statistics/analysis and summarized graphical displays only.  
NONMEM/Pop PK 
File 
Not Applicable. 
NONMEM/PK/PD 
File 
Not applicable. 
 
Pharmacokinetic Parameter Data 
Is NQ impacted PK 
Parameters Rule 
Being Followed 
 
Yes, refer to GUI_51487  
Descriptive 
Summary Statistics, 
Graphical Displays 
and Listings 
Refer to IDSL PK Display Standards.  
Refer to GUI_51487  
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12.6. 
Appendix 6: Derived and Transformed Data 
12.6.1. 
General 
Multiple Measurements at One Analysis Time Point 
• 
Mean of the measurements will be calculated and used in any derivation of summary statistics but if 
listed, all data will be presented. 
• 
If there are two values within a time windowthe value closest to the target day for that window will be 
used. If values are the same distance from the target, then the mean will be taken. 
• 
Participants having both High and Low values for Normal Ranges at any post-baseline visit for safety 
parameters will be counted in both the High and Low categories of “Any visit post-baseline” row of 
related summary tables. This will also be applicable to relevant Potential Clinical Importance 
summary tables. 
Study Day for Safety and PK 
• 
Calculated as the number of days from First Dose Date: 
o Ref Date = Missing              → Study Day = Missing  
o Ref Date < First Dose Date → Study Day = Ref Date – First Dose Date 
o Ref Date ≥ First Dose Date → Study Day = Ref Date – (First Dose Date) + 1     
Study Day for ITT 
• 
Calculated as the number of days from Randomization Date: 
o Ref Date = Missing                                                 → Study Day = Missing  
o Ref Date < Randomization Date → Study Day = Ref Date – Randomization Date 
o Ref Date ≥Randomization Date → Study Day = Ref Date – Randomization Date + 1     
Change from Baseline 
• 
Change from Baseline = Post-Baseline Visit Value – Baseline 
• 
% Change from Baseline= 100 x (Post-Baseline Visit Value – Baseline) / Baseline 
• 
Maximum Increase/Decrease from Baseline = maximum (Increase/Decrease from Baseline) 
• 
If either the Baseline or Post-Baseline Visit Value is missing, Change from Baseline and % Change 
from Baseline is set to missing 
Date of Response 
• For post-baseline disease assessments, the date of response (PR or better) is assigned to the latest 
date of disease assessments; for other response categories (SD [or Non-CR/Non-PD], NE, PD), the 
date of response is assigned to the earliest date of disease assessments.    
Date of New Anti-Cancer Therapy 
• 
Derived as the earliest date of new anti-cancer therapy, radiotherapy (where applicable) or surgical 
procedure (where applicable) 
• Missing or partial dates will be imputed for derivation of new anti-cancer therapy following rules 
specified in Section 12.7.2.1. 
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): 
o If the reference date is on or after the event date, then the elapsed time is the reference date 
minus the event date + 1 
o If the reference date is before the event date, then the elapsed time is the reference date minus 
the event date 
• 
For time to event (TTE) durations such as PFS  
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o To report in months, divide the number of days by 30.4375 
o To report in weeks, divide the number of days by 7 
o 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: 
o To report the duration in weeks divide the number of days by 7 
o To report the duration in months use: (YEAR(stopdate + 1) - YEAR(startdate)) * 12 + 
(MONTH(stopdate + 1) - month(startdate) - 1) + (DAY(stopdate + 1) > = DAY(startdate)) 
o 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))) 
These algorithms 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. 
 
12.6.2. 
Study Population 
Demography 
Age  
• 
Age calculation will be based on Screening Date as the reference Date 
• 
Birth date will be imputed as follows: 
                        Any subject with a missing day will have this imputed as day ‘15’. 
                       Any subject with a missing date and month will have this imputed as ‘30JUN’. 
 
 
Extent of Exposure 
• 
The cumulative dose will be based on the formula: 
Cumulative Dose = Sum of (the actual dose administered during each infusion) 
• 
The relative dose intensity (%) is the infusion dose intensity divided by planned dose per week. 
Relative Dose Intensity = (Cumulative Dose /Planned Dose)*100 
Actual Treatment 
• Participant’s actual treatment will be derived from exposure data. If a participant’s actual treatment is 
the same as assigned treatment, actual treatment is the assigned treatment; if a participant received 
treatment different from assigned treatment for the entire duration of treatment, actual treatment is 
different from assigned treatment. 
Time since Initial Diagnosis 
• 
Calculated as the number of [Days] from the Date of Initial Diagnosis: 
o First Dose Date = Missing           → Elapse Time = Missing  
o Date of Initial Diagnosis = Completely/partially Missing       → Elapse Time = Missing  
o Otherwise       → Elapse Time = First Dose Date – Date of Initial Diagnosis + 1            
 
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12.6.3. 
Safety 
Adverse Events 
AE’S OF Special Interest 
Refer to Section 8.2 
Duration of AE 
• 
Calculated as the number of [days] from AE Start Date to AE Stop Date: 
o AE Start Date = Missing              → Elapse Time = Missing  
o AE Stop Date = Missing              → Elapse Time = Missing 
o Otherwise                                    → Elapsed Time = AE Stop Date – AE Start Date + 1     
 
Laboratory Parameters 
 
• 
If a laboratory value which is expected to have a numeric value for summary purposes, has a non-
detectable level reported in the database, where the numeric value is missing, but typically a 
character value starting with ‘<x’ or ‘>x’ (or indicated as less than x or greater than x in the comment 
field) is present, the number of significant digits in the observed values will be used to determine how 
much to add or subtract in order to impute the corresponding numeric value.  
• 
Example 1: 2 Significant Digits =  ‘< x ‘ becomes x – 0.01 
• 
Example 2: 1 Significant Digit   =  ‘> x’ becomes x + 0.1 
• 
Example 3: 0 Significant Digits = ‘< x’ becomes x – 1 
 
12.6.4. 
Patient Reported Outcomes (PRO) 
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12.7. 
Appendix 7: Reporting Standards for Missing Data 
12.7.1. 
Premature Withdrawals 
Element 
Reporting Detail 
General 
A participant will be considered to have completed the study if the participant dies 
during the study treatment period or follow-up period, whichever is sooner, or is still in 
followup at the time of the final analysis. 
• 
A participant will be considered to have withdrawn from the study if the participant has 
not died and is lost to follow-up, has withdrawn consent, at the investigator’s discretion 
is no longer being followed or if the study is closed/terminated. 
• 
Participants who discontinue will not be replaced in this study. All available data from 
participants who were withdrawn from the study will be listed and all available planned 
data will be included in summary tables and figures, unless otherwise specified.  
12.7.2. 
Handling of Missing Data 
Element 
Reporting Detail 
General 
• 
Missing data occurs when any requested data is not provided, leading to blank 
fields on the collection instrument: 
o These data will be indicated by the use of a “blank” in participant listing 
displays. Unless all data for a specific visit are missing in which case the data 
is excluded from the table.  
o Answers such as “Not applicable” and “Not evaluable” are not considered to be 
missing data and should be displayed as such. 
Outliers 
• 
Any participants excluded from the summaries and/or statistical analyses will be 
documented along with the reason for exclusion in the clinical study report. 
12.7.2.1. 
Handling of Missing and Partial Dates 
Element 
Reporting Detail 
General 
• 
Partial dates will be displayed as captured in participant listing displays. However, 
where necessary, display macros may impute dates as temporary variables for 
sorting data in listings only. In addition, partial dates may be imputed for ‘slotting’ 
data to study phases (see Section 12.4.1) or for specific analysis purposes as 
outlined below. 
• 
Imputed partial dates will not be used to derive study day, time to onset or 
duration (e.g., time to onset or duration of adverse events), or elapsed time 
variables (e.g., time since diagnosis). In addition, imputed dates are not used for 
deriving the last contact date in overall survival analysis dataset. 
Adverse Events 
• 
Imputations in the adverse events dataset are used for slotting events to the 
appropriate study time periods and for sorting in data listings. 
• 
Partial dates for AE recorded in the CRF will be imputed using the following 
conventions: 
 
Missing start day 
• 
If study treatment start date is missing (i.e. participant 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 
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Element 
Reporting Detail 
▪ 
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. 
Missing start day 
and month 
• 
If study treatment start date is missing (i.e. participant 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. 
Missing stop day  
Last day of the month will be used. 
Missing stop day 
and month 
No Imputation 
Completely missing 
start/end date 
No imputation 
Concomitant 
Medications/ 
Blood Supportive 
Products 
• 
Partial dates for any concomitant medications recorded in the CRF will be imputed 
using the following convention: 
 
Missing start day 
• 
If study treatment start date is missing (i.e. participant 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. 
Missing start day 
and month 
• 
If study treatment start date is missing (i.e. participant 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.       
• 
Else set start date = January 1. 
Missing end day 
A '28/29/30/31' will be used for the day (dependent on the month 
and year)  
Missing end day and 
month 
A '31' will be used for the day and 'Dec' will be used for the month. 
Completely missing 
start/end date 
No imputation 
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Element 
Reporting Detail 
New Anti-Cancer 
Therapy/ 
Radiotherapy/ 
Surgical 
Procedures for 
Efficacy 
Evaluation (e.g., 
response rate, 
time to event) 
• 
Completely missing start dates will remain missing, with no imputation applied; 
• 
Partial start dates will be imputed using the following convention: 
• 
If both month and day are missing, no imputation will be applied; 
• 
If only day is missing:  
o If the month of partial date is the same as the month of last dosing date, 
minimum of (last dosing date + 1, last day of the month) will be used for 
the day; 
o If the month of partial date is the same as the month of last disease 
assessment and the last disease assessment is PD, minimum of (last 
date of disease assessment + 1, last day of the month) will be used for 
the day; 
o If both conditions above are met, the later date will be used for the day; 
o Otherwise, a ‘01’ will be used for the day; 
• 
Completely or partial missing end dates will remain missing, with no imputation 
applied; 
ECG 
• 
Missing baseline values are assumed to have baseline value <450  for 
QTc 
 
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12.8. 
Appendix 8: Values of Potential Clinical Importance 
To identify values of potential clinical importance, National Cancer Institute Common 
Terminology Criteria for Adverse Events (NCI-CTCAE v [5.0]) will be used to assign 
grades for laboratory parameters including clinical chemistry, hematology, liver function 
tests, QTc (Fridericia’s) values, LVEF and vital signs (heart rate, blood pressure, 
temperature). 
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. 
 
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12.9. 
Appendix 9: Abbreviations & Trade Marks 
12.9.1. 
Abbreviations 
Abbreviation 
Description 
ADaM 
Analysis Data Model 
ADA 
Anti-drug antibodies 
AE 
Adverse Event 
A&R 
Analysis and Reporting  
CDISC 
Clinical Data Interchange Standards Consortium 
CI 
Confidence Interval 
CPMS 
Clinical Pharmacology Modelling & Simulation 
CR 
Complete Response 
DOB 
Date of Birth 
DOR 
Duration of Response 
DP 
Decimal Places 
eCRF 
Electronic Case Record Form 
FA 
Final Analysis 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Clinical Results Disclosure Requirements 
GSK 
GlaxoSmithKline 
(i)CR 
Complete Response as per (i)RECIST 1.1 
(i)PR 
Partial Response as per (i)RECIST 1.1 
iUPD 
Unconfirmed Progressive disease as per iRECIST 1.1 
iCPD 
Confirmed Progressive Disease as per iRECIST 1.1 
(i)SD 
Stable Disease as per (i)RECIST 1.1 
(i)PFS 
Progression free survival as per (i)RECIST 1.1 
(i)ORR 
Overall response rate as per (i)RECIST 1.1 
(i)DOR 
Duration of Response as per (i)RECIST 1.1 
IA 
Interim Analysis 
ICH 
International Conference on Harmonization 
IDMC 
Independent Data Monitoring Committee  
IDSL 
Integrated Data Standards Library 
IMMS 
International Modules Management System 
ITT 
Intent-To-Treat 
IV 
Intravenous 
IWRS 
Interactive web response system 
LFT 
Liver function test 
LVEF 
Left ventricular ejection fraction 
NCI-CTCAE 
National Cancer Institute - Common Terminology Criteria for Adverse Events 
NSCLC 
Non-small-cell lung cancer 
 
 
ORR 
Overall Response Rate 
OS 
Overall Survival  
PA 
Primary Analysis 
PCI 
Potential Clinical Importance  
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Abbreviation 
Description 
PD 
Progressive Disease 
PFS 
Progression Free Survival 
PDMP 
Protocol Deviation Management Plan 
PK 
Pharmacokinetic 
PP 
Per Protocol 
PR 
Partial Response 
PRO 
Patient-reported outcome  
 
 
 
 
 
 
 
QoL 
Quality of Life 
QTcF 
Frederica’s QT Interval Corrected for Heart Rate 
QTcB 
Bazett’s QT Interval Corrected for Heart Rate 
RAP 
Reporting & Analysis Plan 
RAMOS 
Randomization & Medication Ordering System  
RECIST  
Response evaluation criteria in solid tumours 
SAC 
Statistical Analysis Complete 
SD 
Stable Disease 
SDTM 
Study Data Tabulation Model 
SoC 
Standard of Care 
SOC 
System Organ Class 
SOP 
Standard Operation Procedure 
TA 
Therapeutic Area 
TFL 
Tables, Figures & Listings  
12.9.2. 
Trademarks 
Trademarks of the GlaxoSmithKline 
Group of Companies 
 
Trademarks not owned by the 
GlaxoSmithKline Group of Companies 
NONE 
 
SAS 
 
 
WinNonLin 
 
 
 
 
 
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12.10. 
Appendix 10: List of Data Displays 
12.10.1. 
Data Display Numbering 
The following numbering will be applied for RAP generated displays: 
Section 
Tables 
Figures 
Study Population 
1.1 to 1.23 
 
Efficacy 
2.1 to 2.12 
2.1 to 2.6 
Safety 
3.1 to 3.34 
3.1 to 3.2 
Pharmacokinetic 
4.1 to 4.4 
4.1 to 4.6 
Patient Reported Outcome 
5.1 to 5.12 
5.1 to 5.6 
Section 
Listings 
ICH Listings 
1 to 35 
Other Listings 
36 to 44 
 
12.10.2. 
Mock Example Shell Referencing 
Non IDSL specifications will be referenced as indicated and if required example mock-up 
displays provided in Section 12.11: Example Mock Shells for Data Displays. 
 
Section 
Figure 
Table 
Safety 
 
SAFE_Tn 
Patient Reported Outcome 
PRO_Fn 
PRO_Tn 
 
12.10.3. 
Deliverables 
Delivery  
Description 
Part 1 
Futility analysis 
IDMC  
Independent Data Monitoring Committee Open session 
PA 
Primary Analysis 
FA 
Final Statistical Analysis Complete 
 
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12.10.4. 
Study Population Tables 
Study Population Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Subject Disposition 
1.1. 
ITT/Safety 
ES8  
 
Summary of Subject Status and Reason for Study Withdrawal 
ICH E3, FDAAA, EudraCT 
Part 1 is based on Safety population 
Part 2 is based on ITT population 
PART1, 
IDMC/PA. 
FA,(Headline) 
1.2. 
Safety 
SD4 
Summary of Treatment Status and Reasons for Discontinuation 
of Study Treatment 
ICH E3 
 
PART1, IDMC/ 
PA. FA, 
(Headline) 
1.3. 
Screened 
ES6 
Summary of Screening Status and Reasons for Screen Failure 
Journal Requirements 
 
PART1, IDMC/ 
PA. FA, 
1.4. 
ITT/Safety 
NS1 
Summary of Number of Participant by Country and Site ID 
EudraCT/Clinical Operations 
Part 1 is based on Safety population 
Part 2 is based on ITT population 
PART1, IDMC/ 
PA. FA, 
1.5. 
Screened 
SP1  
 
Summary of Study Populations  
IDSL 
 
PART1, PA. FA, 
Protocol Deviation 
1.6. 
ITT/Safety 
DV1 
Summary of Protocol Deviations 
ICH E3 
Part 1 is based on Safety population 
Part 2 is based on ITT population 
 
Separate the page by important and 
non-important deviations 
PART1, PA. FA, 
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Study Population Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Demographics  
1.7. 
ITT/Safety 
DM1  
Summary of Demographic Characteristics 
ICH E3, FDAAA, EudraCT 
Include baseline stratification factors 
Part 1 is based on Safety population 
Part 2 is based on ITT population 
PART1, IDMC/ 
PA. FA, 
(Headline) 
1.8. 
ITT/Safety 
DM11 
Summary of Age Ranges 
EudraCT 
Part 1 is based on Safety population 
Part 2 is based on ITT population 
PART1, IDMC/ 
PA. FA, 
1.9. 
ITT/Safety 
DM5 
Summary of Race and Racial Combinations 
ICH E3, FDA, FDAAA, EudraCT  
Part 1 is based on Safety population 
Part 2 is based on ITT population 
PART1, IDMC/ 
PA. FA, 
Prior and Concomitant Medications 
1.10. 
ITT/Safety 
MH1  
 
Summary of Past Medical Conditions 
ICH E3  
Part 1 is based on Safety population 
Part 2 is based on ITT population 
PART1, IDMC/ 
PA. FA, 
1.11. 
ITT/Safety 
MH1  
 
Summary of Current Medical Conditions 
ICH E3  
Part 1 is based on Safety population 
Part 2 is based on ITT population 
PART1, IDMC/ 
PA. FA, 
1.12. 
ITT/Safety 
CM1  
 
Summary of Concomitant Medications  
ICH E3 
Part 1 is based on Safety population 
Part 2 is based on ITT population 
PART1, PA. FA, 
Disease Characteristics 
1.13. 
ITT 
DC1 
Summary of Disease Characteristics at Initial Diagnosis 
ICH E3 
IDMC/ PA. FA, 
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Study Population Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.14. 
ITT 
DC2 
Summary of Disease Characteristics at Baseline 
ICH E3  
Add definitions for progression 
and recurrence 
IDMC/ PA. FA, 
(Headline) 
1.15. 
ITT 
MD1 
Summary of Metastatic Disease at Screening 
 
IDMC/ PA. FA, 
1.16. 
ITT 
LA1 
Summary of Disease Burden at Baseline 
ICH E3 
 
IDMC/ PA. FA, 
Anti-Cancer Therapy 
1.17. 
ITT/Safety 
AC1  
 
Summary of Prior Anti-Cancer Therapy 
IDSL 
Part 1 is based on Safety population 
Part 2 is based on ITT population 
PART1, IDMC/ 
PA. FA, 
1.18. 
ITT/Safety 
CM1 
Summary of Prior Dictionary Coded Anti-Cancer Therapy 
IDSL 
Part 1 is based on Safety population 
Part 2 is based on ITT population 
PART1, IDMC/ 
PA. FA, 
1.19. 
ITT/Safety 
AC3 
Summary of Number of Prior Anti-Cancer Therapy Regimens 
IDSL 
Part 1 is based on Safety population 
Part 2 is based on ITT population 
PART1, IDMC/ 
PA. FA, 
1.20. 
ITT/Safety 
FAC1 
Summary of Follow-up Anti-Cancer Therapy 
IDSL 
Part 1 is based on Safety population 
Part 2 is based on ITT population 
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Study Population Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Surgical/Medical Procedures 
1.21. 
ITT/Safety 
OSP1  
 
Summary of Prior Surgical Procedures 
IDSL 
Part 1 is based on Safety population 
Part 2 is based on ITT population 
PART1, IDMC/ 
PA. FA, 
Substance Use 
1.22. 
ITT 
SU1 
Summary of Substance Use  
IDSL 
 
IDMC/ PA. FA, 
Follow-up 
1.23. 
ITT 
FAC2 
Summary of Duration of Follow-up 
 
PA. FA, 
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12.10.5. 
Efficacy Tables 
Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Responses  
2.1.  
ITT /Safety 
RE1a  
 
Summary of Confirmed Investigator-Assessed Best Response 
(RECIST1.1)  
 
Add rows for DCR 
(CR+PR+SD), Odds ratio for 
DCR, 95% CI and p-Value 
Part 1 is based on Safety population 
Part 2 is based on ITT population 
 
PART1,  PA. 
FA,(Headline) 
2.2.  
ITT 
RE1a 
Summary of Confirmed Investigator-Assessed Best Response 
(iRECIST Criteria) 
Add rows for DCR 
(CR+PR+SD), Odds ratio for 
DCR, 95% CI and p-Value 
PA. FA, 
2.3.  
ITT 
RE2 
Summary of Investigator Assessed Response Rate with 
confirmation (RECIST1.1 Criteria) by Stratification Factors  
 
• 
Histology (squamous vs. non 
squamous) and line of PD(L)1 
therapy (1st vs. 2nd line). 
• 
Add Count and percentages 
for DCR ( CR+PR+SD) 
PA. FA, 
2.4.  
ITT 
RE2 
Summary of Investigator Assessed Response Rate with 
confirmation (iRECIST Criteria)  by Stratification Factors  
 
Add Count and percentages for DCR ( 
CR+PR+SD) 
PA. FA, 
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Time-to-event Endpoints 
2.5.  
ITT 
TTE3 
Summary of Kaplan-Meier Estimates of Progression-Free 
Survival  
 
Using RECIST1.1 followed by iRECIST 
on next page 
Do not report p-values 
PA. 
FA,(Headline) 
2.6.  
ITT 
TTE3 
Summary of Kaplan-Meier Estimates of Overall Survival  
 
Do not report p-values 
PA. 
FA,(Headline) 
2.7.  
ITT 
TTE6 
Summary of Kaplan-Meier Estimates of Overall Survival at 12 
and 18 Months  
 
PA. FA, 
2.8.  
ITT 
TTE1 
Summary of Kaplan-Meier Estimates of Duration of Response  
in Subjects with Objective Response 
 
 
Page by RECIST1.1 then iRECIST 
PA. 
FA,(Headline) 
2.9.  
ITT 
TTE4 
Summary of Cox Proportional Hazards Regression Model for 
Overall Survival 
Remove p-value column 
Include a row for predictive probability 
of Phase 3 success as the last segment 
 
 
PA. 
FA,(Headline) 
2.10. 
 
 
Model Diagnostic SAS outputs from Cox Proportional Hazards 
model for Overall Survival 
RTF format of SAS results output 
PA. FA, 
2.11. 
ITT 
TTE4 
Summary of Cox Proportional Hazards Regression Model for 
Overall Survival (Sensitivity Analysis for Adjusting the Impact of 
COVID 19) 
 
PA. FA, 
2.12. 
ITT 
TTE4 
Summary of Cox Proportional Hazards Regression Model for 
Progression Free Survival  
Remove p-value column 
Page by RECIST 1.1 then iRECIST 
PA. FA, 
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Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Responses  
2.1.  
ITT /Safety 
RE1a  
 
Summary of Confirmed Investigator-Assessed Best Response 
(RECIST1.1)  
 
Add rows for DCR 
(CR+PR+SD), Odds ratio for 
DCR, 95% CI and p-Value 
Part 1 is based on Safety population 
Part 2 is based on ITT population 
 
PART1,  PA. 
FA,(Headline) 
2.2.  
ITT 
RE1a 
Summary of Confirmed Investigator-Assessed Best Response 
(iRECIST Criteria) 
Add rows for DCR 
(CR+PR+SD), Odds ratio for 
DCR, 95% CI and p-Value 
PA. FA, 
2.3.  
ITT 
RE2 
Summary of Investigator Assessed Response Rate with 
confirmation (RECIST1.1 Criteria) by Stratification Factors  
 
• 
Histology (squamous vs. non 
squamous) and line of PD(L)1 
therapy (1st vs. 2nd line). 
• 
Add Count and percentages 
for DCR ( CR+PR+SD) 
PA. FA, 
2.4.  
ITT 
RE2 
Summary of Investigator Assessed Response Rate with 
confirmation (iRECIST Criteria)  by Stratification Factors  
 
Add Count and percentages for DCR ( 
CR+PR+SD) 
PA. FA, 
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Time-to-event Endpoints 
2.5.  
ITT 
TTE3 
Summary of Kaplan-Meier Estimates of Progression-Free 
Survival  
 
Using RECIST1.1 followed by iRECIST 
on next page 
Do not report p-values 
PA. 
FA,(Headline) 
2.6.  
ITT 
TTE3 
Summary of Kaplan-Meier Estimates of Overall Survival  
 
Do not report p-values 
PA. 
FA,(Headline) 
2.7.  
ITT 
TTE6 
Summary of Kaplan-Meier Estimates of Overall Survival at 12 
and 18 Months  
 
PA. FA, 
2.8.  
ITT 
TTE1 
Summary of Kaplan-Meier Estimates of Duration of Response  
in Subjects with Objective Response 
 
 
Page by RECIST1.1 then iRECIST 
PA. 
FA,(Headline) 
2.9.  
ITT 
TTE4 
Summary of Cox Proportional Hazards Regression Model for 
Overall Survival 
Remove p-value column 
Include a row for predictive probability 
of Phase 3 success as the last segment 
 
 
PA. 
FA,(Headline) 
2.10. 
 
 
Model Diagnostic SAS outputs from Cox Proportional Hazards 
model for Overall Survival 
RTF format of SAS results output 
PA. FA, 
2.11. 
ITT 
TTE4 
Summary of Cox Proportional Hazards Regression Model for 
Overall Survival (Sensitivity Analysis for Adjusting the Impact of 
COVID 19) 
 
PA. FA, 
2.12. 
ITT 
TTE4 
Summary of Cox Proportional Hazards Regression Model for 
Progression Free Survival  
Remove p-value column 
Page by RECIST 1.1 then iRECIST 
PA. FA, 
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12.10.6. 
Efficacy Figures 
Efficacy: Figures 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Response 
2.1
ITT 
RE8a  
 
Investigator-Assessed Maximum Percent Reduction from 
Baseline in Tumor Measurement (RECIST1.1) 
 
PART1,  PA. 
FA, 
Time-to-Event Endpoints 
2.2.  
ITT 
TTE10 
Graph of Kaplan Meier Survival Curves for Progression Free 
Survival  with 95% Confidence Band   
 
Page by RECIST1.1 then iRECIST.  
PA. 
FA,(Headline) 
2.3.  
ITT 
TTE10 
Graph of Kaplan Meier Curves for Overall Survival 
Include line at 12 months and 18 
months to approximate the rate and 
95% CI. 
 
PA. 
FA,(Headline) 
2.4.  
ITT 
TTE10 
Graph of Kaplan Meier Curves for Duration of Response in 
Subjects with Objective Response 
 
Page by RECIST1.1 then iRECIST 
PA. FA, 
2.5.  
ITT 
TTE11 
Forest Plot of r Overall Survival by Subgroup 
 
PA. 
FA,(Headline) 
2.6.  
ITT 
TTE11 
Forest Plot of  Progression Free Survival by RECIST1.1. by 
Subgroup 
 
PA. FA, 
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12.10.7. 
Safety Tables 
Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Adverse Events (AEs) 
3.1.  
Safety 
 
AE5B 
Summary of Treatment Emergent Adverse Events by System 
Organ Class and Preferred Term and Maximum Grade 
 
 
PART1, PA. FA, 
3.2.  
Safety 
OAE07 
Summary of Treatment Emergent Adverse Events by Preferred 
Term and Maximum Grade 
 
PART1, PA. FA, 
(Headline) 
3.3.  
 
 
 
Safety  
AE13 
Treatment Emergent Adverse Events Overview 
Include Any AE, AEs related to study 
treatment,leading to permanent 
discontinuation of study 
treatment,leading to dose 
reduction,leading to dose 
interruption/delay, Any SAE,SAEs 
related to study treatment,Fatal 
SAEs,Fatal SAEs related to study 
treatment 
Add an additional row to indicate 
frequency and percentage of Treatment 
Related AE’s of grade 3+4+5 
 
 
 
PART1, PA. FA, 
(Headline) 
3.4.  
Safety 
AE3 
Summary of Common (>=5%) Grade 3-5 Treatment Emergent 
Adverse Events by Overall Frequency 
 
PART1, PA. FA, 
(Headline) 
3.5.  
 
Safety 
OAE01 
Summary All Drug-Related Treatment Emergent Adverse Events 
by System Organ Class and Preferred Term and Maximum 
Grade 
 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.6.  
Safety 
AE15 
Summary of Common (>=5%) Non-serious Treatment Emergent 
Adverse Events by System Organ Class and Preferred Term 
(Number of Participant and Occurrences) 
 
PART1, PA. FA, 
3.7.  
Safety 
AE3 
Summary of Common (>=5%) Drug-Related Grade 3-5 
Treatment Emergent Adverse Events by Overall Frequency 
 
PART1, PA. FA, 
3.8.  
Safety 
AE3 
Summary of Non-Serious Drug-Related Treatment Emergent 
Adverse Events by Overall Frequency 
 
PART1, PA. FA, 
Adverse Events of Special Interest 
3.9.  
Safety 
OAE01 
 
Summary of Adverse Event or Condition of Special interest by 
Preferred Term and Maximum Grade 
 
PART1, PA. FA, 
3.10. 
Safety 
ESI2a 
Summary of Onset and Duration of the First Occurrence of AE of 
Special Interest 
 
PART1, PA. FA, 
Serious and Other Significant Adverse Events 
3.11. 
Safety 
AE16 
Summary of Serious Treatment Emergent Adverse Events by 
System Organ Class and Preferred Term (Number of 
Participants and Occurrences) 
FDAAA, EudraCT 
 
PART1, PA. FA, 
(Headline) 
3.12. 
Safety 
AE3 
Summary of Treatment Emergent Adverse Events Leading to 
Permanent Discontinuation of Study Treatment by Preferred 
Term 
 
PART1, PA. FA, 
Deaths 
3.13. 
Safety 
DTH1a 
 
Summary of Deaths 
IDSL 
 
PART1, PA. FA, 
(Headline) 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Laboratory: Chemistry  
3.14. 
Safety 
LB1 
Summary of Chemistry Changes from Baseline  
ICH E3 
 
PART1, PA. FA, 
3.15. 
Safety 
OLB9C 
Summary of Worst Case Chemistry Results by Maximum 
Grade Increase Post-Baseline Relative to Baseline 
ICH E3 
 
 
 
 
PART1, PA. FA, 
3.16. 
Safety 
OLB11C 
Summary of Worst Case Chemistry Results Relative to Normal 
Range Post-Baseline Relative to Baseline 
ICH E3 
 
 
PART1, PA. FA, 
Laboratory: Hematology 
3.17. 
Safety 
LB1 
Summary of Hematology Changes from Baseline 
ICH E3 
 
PART1, PA. FA, 
3.18. 
Safety 
OLB9C 
Summary of Worst Case Hematology Results by Maximum 
Grade Increase Post-Baseline Relative to Baseline 
ICH E3 
 
PART1, PA. FA, 
3.19. 
Safety 
OLB11C 
Summary of Worst Case Hematology Results Relative to Normal 
Range Post-Baseline Relative to Baseline 
ICH E3 
 
PART1, PA. FA, 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Laboratory: Urinalysis 
3.20. 
Safety 
LB1 
Summary of Urinalysis Results 
ICH E3 
 
PART1, PA. FA, 
3.21. 
Safety 
OUR1B 
 
Summary of Worst Case Urinalysis Results (Discrete or 
Character Values) Post-Baseline Relative to Baseline 
ICH E3 
 
PART1, PA. FA, 
Laboratory: Hepatobiliary (Liver) 
3.22. 
Safety 
OLIVER1 
Summary of Hepatobiliary Laboratory Abnormalities 
IDSL 
 
PART1, PA. FA, 
Vital Signs 
3.23. 
Safety 
OVT1B 
Summary of Changes in Vital Signs from Baseline 
 
PART1, PA. FA, 
Exposure/Dose Modifications 
3.24. 
Safety 
SAFE_T1 
Summary of Exposure to Treatment 
Add a footnote defining the “Cycle” 
PART1, PA. FA, 
(Headline) 
3.25. 
Safety 
ODMOD4 
Summary of Missed Doses by Component 
Exclude the last segment “Number of 
Subjects with Missed Doses by 
Planned Time” 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.26. 
Safety 
ODMOD1 
Summary of Dose Reductions  
Exclude the last segment “Number of 
Subjects with Dose Reduction by 
Planned Time”. Count number of 
participants and total number of 
reductions if either component is 
reduced. Summarise details on number 
and reason by component in separate 
rows 
PART1, PA. FA, 
3.27. 
Safety 
ODMOD3 
Summary of Dose Delays  
Exclude the last segment “Number of 
Subjects with Dose Delays by Planned 
Time”. Count number of participants 
and total number of delays if either 
component is delayed. Summarise 
details on number, duration and reason 
by component in separate rows 
PART1, PA. FA, 
3.28. 
Safety 
ODMOD9 
Summary of Incomplete Infusions 
Exclude the last segment “Number of 
Subjects with Incomplete Infusions by 
Planned Time” 
PART1, PA. FA, 
3.29. 
Safety 
ODMOD16 
Summary of Infusion Interruptions 
Exclude the last segment” Number of 
Subjects with Infusion Interruptions by 
Planned Time” 
PART1, PA. FA, 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Performance Status 
3.30. 
Safety 
PS1A  
 
Summary of ECOG Performance Status 
ICH E3 
 
PART1, PA. FA, 
Immunogenecity 
3.31. 
Safety 
IMM1 
Summary of Positive Immunogenecity Results 
 
PART1, PA. FA, 
COVID-19 Assessments 
3.32. 
Safety 
PAN1 
Summary of COVID-19 Assessments for Subjects with COVID-
19 Adverse Events  
 
PART1, PA. FA, 
3.33. 
Safety 
PAN3 
Summary of COVID-19 Symptoms for Subjects with COVID-19 
Adverse Events  
 
PART1, PA. FA, 
Dose Limiting Toxicity (DLT 
3.34. 
DLT 
Evaluable 
AE19 
Summary of Dose-Limiting Toxicities during the Determinative 
Period (DE Phase) 
 
PART1 
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12.10.8. 
Safety Figures 
Safety: Figures 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Exposure 
3.1.  
Safety 
OEX12 
Plot of Duration of Study Treatment 
 
PA. FA, 
Laboratory 
3.2.  
Safety 
Liver9 
Scatter Plot of Maximum Bilirubin versus Maximum ALT – 
eDISH 
 
PA. FA, 
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12.10.9. 
Pharmacokinetic Tables 
Pharmacokinetic: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
PK 
4.1.  
PK 
PK01 
Summary of GSK3359609 Plasma Concentration Time Data 
IDSL 
FA, SAC 
4.2.  
PK 
PK01 
Summary of Docetaxel Plasma Concentration Time Data  
IDSL 
FA, SAC 
4.3.  
PK 
PK06 
Summary of Derived GSK3359609 Pharmacokinetic 
Parameters (non-transformed and log-transformed) 
IDSL 
FA, SAC 
4.4.  
PK 
PK06 
Summary of Derived Docetaxel Parameters (non-transformed 
and log-transformed) 
IDSL 
FA, SAC 
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12.10.10. Pharmacokinetic Figures 
Pharmacokinetic: Figures 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
PK 
4.1.  
PK 
PK16a 
Individual GSK3359609 Plasma Concentration-Time Plot by 
Subject (Linear and Semi-Log)  
 
IDSL 
 
FA, SAC 
4.2.  
PK 
PK16a 
Individual Docetaxel Plasma Concentration-Time Plot by 
Subject (Linear and Semi-Log)  
 
IDSL 
 
FA, SAC 
4.3.  
PK 
PK17 
Mean GSK3359609 Concentration-Time Plots (Linear and 
Semi-log) 
IDSL 
 
FA, SAC 
4.4.  
PK 
PK17 
Mean Docetaxel Concentration-Time Plots (Linear and Semi-
log) 
IDSL 
 
FA, SAC 
4.5.  
PK 
PK18 
Median GSK3359609 Concentration-Time Plots (Linear and 
Semi-log) 
IDSL 
 
FA, SAC 
4.6.  
PK 
PK18 
Median Docetaxel Concentration-Time Plots (Linear and Semi-
log) 
IDSL 
 
FA, SAC 
 
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12.10.11. Patient Reported Outcomes Tables 
Patient Reported Outcome: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
 
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Patient Reported Outcome: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
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Patient Reported Outcome: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
 
 
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12.10.12. Patient Reported Outcomes Figures 
Patient Reported Outcome: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
 
 
 
 
 
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12.10.13. ICH Listings 
ICH: Listings 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Subject Disposition 
1.  
Screened 
ES7 
Listing of Reasons for Screen Failure 
Journal Guidelines 
Part1, IDMC/ 
PA. FA, 
2.  
ITT/Safety 
ES2  
 
Listing of Reasons for Study Withdrawal 
ICH E3 
Part 1 is based on Safety population 
Part 2 is based on ITT population 
Part1, IDMC/ 
PA. FA, 
3.  
Safety 
SD2  
 
Listing of Reasons for Study Treatment Discontinuation 
ICH E3 
 
Part1,IDMC/ PA. 
FA, 
4.  
ITT 
TA1  
 
Listing of Planned and Actual Treatments 
IDSL 
 
PA. FA, 
Protocol Deviations 
5.  
ITT/Safety 
DV2 
Listing of Important Protocol Deviations  
ICH E3 
Part 1 is based on Safety population 
Part 2 is based on ITT population 
Part1, PA. FA, 
6.  
ITT/Safety 
IE3  
 
Listing of Participants with Inclusion/Exclusion Criteria 
Deviations 
ICH E3 
Part 1 is based on Safety population 
Part 2 is based on ITT population 
Part1, IDMC/ 
PA. FA, 
Demographic and Baseline Characteristics 
7.  
ITT/Safety 
DM2  
 
Listing of Demographic Characteristics 
ICH E3 
Part 1 is based on Safety population 
Part 2 is based on ITT population 
Part1, IDMC/ 
PA. FA, 
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ICH: Listings 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
8.  
ITT/Safety 
DM9  
 
Listing of Race 
ICH E3 
Part 1 is based on Safety population 
Part 2 is based on ITT population 
Part1, IDMC/ 
PA. FA, 
Prior and Concomitant Medications 
9.  
ITT/Safety 
CP_CM3  
Listing of Prior/Concomitant Medications 
IDSL 
Part 1 is based on Safety population 
Part 2 is based on ITT population 
Part1, PA. FA, 
10.  
ITT/Safety 
MH2 
Listing of Past/Current Medical Conditions 
Oncology specific template to be 
used 
Part 1 is based on Safety population 
Part 2 is based on ITT population 
Part1, IDMC/ 
PA. FA, 
Exposure and Treatment Compliance 
11.  
Safety 
OEX8a 
Listing of Exposure to Docetaxel 
ICH E3 
 
PA. FA, 
12.  
Safety 
OEX8b 
Listing of Exposure to GSK3359609 
ICH E3 
 
Part1, PA. FA, 
13.  
Safety 
COMP2 
Listing of Overall Compliance 
 
Part1, IDMC/ 
PA. FA, 
Dose Modifications 
14.  
Safety 
 
ODMOD10A  
 
Listing of Dose Reductions 
Exclude Cycle  
Part1, PA. FA, 
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ICH: Listings 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
15.  
Safety 
ODMOD17A  
 
Listing of Infusion Interruptions 
Exclude Cycle  
Part1, PA. FA, 
16.  
Safety 
ODMOD14A 
Listing of Incomplete Infusions 
Exclude Cycle Day 
Part1, PA. FA, 
17.  
Safety 
ODMOD12A  
 
Listing of Dose Delays 
Exclude Cycle Day 
Part1, PA. FA, 
18.  
Safety 
ODMOD13A  
 
Listing of Missed Doses 
Exclude Cycle  
Part1, PA. FA, 
Response 
19.  
ITT/Safety 
LA5 
Listing of Investigator Assessed Lesion Assessments 
(RECIST 1.1 Criteria) 
Include Target Lesions,Non-Target 
Lesions and New  
Part 1 is based on Safety population 
Part 2 is based on ITT population 
Part1, PA. FA, 
20.  
ITT 
LA5 
Listing of Investigator Assessed Lesion Assessments 
(iRECIST Criteria) 
Include Target Lesions,Non-Target 
Lesions and New Lesions 
PA. FA, 
21.  
ITT/Safety 
RE5 
Listing of Investigator Assessed Responses with confirmation 
(RECIST 1.1 Criteria) 
Part 1 is based on Safety population 
Part 2 is based on ITT population 
Part1, PA. FA, 
22.  
Safety/ITT 
RE5 
Listing of Investigator Assessed Responses with confirmation 
(iRECIST Criteria) 
Part 1 is based on Safety population 
Part 2 is based on ITT population 
Part1, PA. FA, 
Adverse Events 
23.  
Safety 
AE8  
Listing of All Adverse Events 
ICH E3 
Part1, PA. FA, 
24.  
Safety 
AE7 
Listing of Subject Numbers for Individual Adverse Events 
ICH E3 
Part1, PA. FA, 
25.  
Safety 
AE2 
Listing of Relationship Between Adverse Event System 
Organ Classes, Preferred Terms, and Verbatim Text 
IDSL 
Part1, PA. FA, 
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ICH: Listings 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Adverse Events of Special Interest 
26.  
Safety 
AE8  
Listing of AE of Special Interest 
 
Part1, PA. FA, 
Serious and Other Significant Adverse Events 
27.  
Safety 
AE14 
Listing of Reasons for Considering as a Serious Adverse 
Event 
ICH E3 
Part1, PA. FA, 
28.  
Safety 
AE8  
Listing of Adverse Events Leading to Withdrawal from Study / 
Permanent Discontinuation of Study Treatment 
ICH E3 
Part1, PA. FA, 
Deaths 
29.  
Safety 
DTH3  
 
Listing of Deaths 
ICH E3 
 
Part1, PA. FA, 
Hepatobiliary (Liver) 
30.  
Safety 
MH2 
Listing of Medical Conditions for Participants with Liver 
Stopping Events 
IDSL 
Part1, PA. FA, 
31.  
Safety 
SU2 
Listing of Substance Use for Participants with Liver Stopping 
Events 
IDSL 
Part1, PA. FA, 
All Laboratory 
32.  
Safety 
LB5  
 
Listing of All Laboratory Data for Participants with Any Value 
of Potential Clinical Importance 
ICH E3 
 
Part1, PA. FA, 
33.  
Safety 
LB14 
Listing of Laboratory Data with Character Results 
ICH E3 
Part1, PA. FA, 
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ICH: Listings 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Performance Status 
34.  
Safety 
PS5A 
Listing of Performance Status 
 
Part1, PA. FA, 
Dose-Limiting Toxicities 
35.  DLT Evaluable 
MTD_DLDL1 
Listing of Dose-Limiting Toxicities (DLT) during the 
determinative period (DE Phase)  
 
Part1 
 
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12.10.14.  Non-ICH Listings 
Non-ICH: Listings 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Disease Characteristics 
36.  
ITT 
DC3 
Listing of Disease Characteristics at Initial Diagnosis 
 
IDMC/ PA. FA, 
37.  
ITT 
DC4 
Listing of Disease Characteristics at Screening 
 
IDMC/ PA. FA, 
Anti-Cancer Therapy 
38.  
ITT 
AC6 
Listing of Prior Anti-Cancer Therapy 
 
IDMC/ PA. FA, 
39.  
ITT 
AC7 
Listing of Prior Anti-Cancer Radiotherapy 
 
IDMC/ PA. FA, 
40.  
ITT 
FAC3 
Listing of Follow-Up Anti-Cancer Therapy 
 
PA. FA, 
Surgical Procedures 
41.  
ITT 
OSP3 
Listing of Prior Surgical Procedures 
 
PA. FA, 
Immunogenecity 
42.  
Safety 
IMM2 
Listing of Immunogenicity Results 
 
PA. FA, 
PK 
43.  
PK 
PK07  
Listing of Pharmacokinetic Concentration-Time Data by Analyte 
IDSL 
PA. FA, 
44.  
PK 
PK13  
Listing of Derived Pharmacokinetic Parameters by Analyte 
IDSL 
PA. FA, 
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12.11. 
Appendix 11: Example Mock Shells for Data Displays 
Data Display Specification will be made available on request. 
 
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12.12. 
Appendix 12: SDAC REPORTING PLAN  
GSK Protocol 205801 - GSK3359609 ENTREE Study  
Version:  Final  
Date:  20 February 2020  
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13. 
INTRODUCTION  
This document, the SDAC Reporting Plan for GSK Protocol 205801, describes SDAC’s 
proposal for the initial content and structure of Independent Data Monitoring Committee 
(IDMC) reports.  It includes general statistical analysis conventions and a detailed 
proposed table of contents.  Mock tables, figures, and listings are provided in a 
companion document, the SDAC Sample Report.  
This document is the final version of SDAC Reporting Plan for GSK Protocol 205801. 
The drafted version (and the companion SDAC Sample Report) has been distributed to the 
DMC and GSK prior to the first IDMC meeting for review and discussion.    
The IDMC, SDAC, and GSK recognize that for the IDMC to effectively execute their 
responsibility to oversee the safety of subjects enrolled in the study, they will require 
interim reporting that meets their needs as those needs evolve over the duration of the 
studies.  As such, this proposal is intended as a general guide for the content and structure 
of initial reports to be produced by SDAC for the IDMC and it is not intended to either 
limit the scope of the analyses the IDMC may request or to require a particular form or 
structure for an analysis.  It is understood that the IDMC will have the final authority to 
specify, on an ongoing basis, the content and structure of the reports they receive.  
13.1. 
References to External Documents  
Where this document excerpts or references external documents, the following versions 
have been used:  
• 
IDMC Charter (Version 001, dated December 19, 2018)   
• 
SDAC Sample Report (dated September 20, 2016)  
• 
Study Protocol (205801 Amendment #1 dated September 20, 2018)  
• 
Study RAP (Statistical Analysis Plan Reporting and Analysis Plan dated December 
13, 2018)  
• 
AESI Listing (GSK3359609 AESI list FINAL 03Apr19 - Version 1.xlsx)  
13.2. 
OVERVIEW OF ANALYSES SPECIFIED IN THE IDMC 
CHARTER  
SDAC will prepare both open session and closed session reports containing summaries of 
safety and/or efficacy data for data review meetings starting when adequate data are 
available. Data review meetings will be held at least every 6 months, but more frequent 
meetings may be held.   
As described in the IDMC Charter, the IDMC will review the following data for study 
205801: “Summarized unblinded safety data including AEs, SAEs, immune-related 
adverse events (irAEs), adverse events of special interest (AESI), and laboratory data for 
all active substudies. Summarized unblinded efficacy data primary endpoints and selected 
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secondary endpoints such as ORR, PFS, etc.  Note that if a substudy or treatment arm has 
been discontinued, this data will not require further review.”  
As such, the safety reports from each of the studies will contain, at a minimum, analyses 
of all adverse events, serious adverse events (including deaths and SUSARs if recorded), 
withdrawals due to adverse events, laboratory values, and available efficacy data. All 
IDMC recommendations will be made based on a review of the totality of evidence.   
As stated in the IDMC Charter, Section 3.5, “At the planned interim analyses in the 
205801 study, the IDMC may make the recommendation to halt an individual substudy or 
study treatment arm (other than SoC) due to safety concerns and/or lack of efficacy.” 
Additionally, the IDMC may recommend the discontinuation of an experimental regimen 
based on the totality of evidence to protect the safety, in relation to efficacy, of 
participating subjects. As such, closed session reports will include primary interim 
efficacy measures. Open session reports will omit these analyses to preserve blinding.  
  
The details of these reports are described in Section 13.4.  
13.3. 
GENERAL SDAC REPORTING CONVENTIONS  
13.3.1. 
Sample Report  
The separate document titled SDAC Sample Report provides an example of IDMC report 
content and format for a single, fictitious protocol based on simulated data.  This 
fictitious protocol is patterned after a typical cardiovascular study, and therefore the 
example analyses are not tailored to the specifics of this study’s design.  
Actual reports for the GSK 205801 study will include initial content as proposed in detail 
in Section 4 below.  
In the remainder of this document, references in doubled square brackets are to pages 
of the Sample Report (e.g., [[Figure ACCR-1, p. 18]]).  
13.3.2. 
Open and Closed Session Reports  
SDAC will produce Closed Session and Open Session versions of IDMC reports.  
Closed Session reports will include analyses of all relevant data by treatment group.  
These reports will be only for review by the IDMC and will not be shared with other 
parties prior to database lock for the study.  Treatment groups will be identified by single-
letter codes with assignment of codes to treatment arms provided to the IDMC members 
in a separate document.  Codes will be consistent between reports over the life of the 
trial.  
Open session reports will include displays of aggregate data only (no treatment group 
information) and so will be fully blinded.  Open session reports will also exclude efficacy 
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analyses and any additional analyses requested by the IDMC on the basis of their 
unblinded review.  Open session reports will be provided to all open session participants, 
including the IDMC and GSK.  
13.3.3. 
General Analysis Conventions  
Reports will include analyses of all randomized subjects restricted to (1) post-
randomization event data and (2) baseline and post-randomization data from other 
sources.  In particular, analyses will exclude subjects that are screened but not 
randomized and will exclude any adverse events occurring prior to randomization.  
All analyses will be performed on an intention-to-treat basis with subjects analyzed as 
randomized irrespective of adherence to treatment.  In particular, analyses will include 
data collected for subjects who discontinue treatment but remain on study.   
In general, for follow-up data collected on a per-visit basis (e.g., laboratory 
measurements and vital signs) that include a visit code and a visit date, analyses by 
scheduled visit will use the visit code rather than applying a windowing algorithm to the 
visit date, and unscheduled visits will be excluded.  Analyses that aggregate postbaseline 
data (e.g., plots showing numbers of subjects who ever had a post-baseline, abnormal 
value for a laboratory measurement) will use all post-baseline measurements, whether 
scheduled or unscheduled.  
13.3.4. 
Graphical Conventions  
The primary mode of presentation in SDAC IDMC reports is graphical; most presented 
graphics have supporting back-up tables in the Supporting Material section of the report 
(see SDAC Sample Report, p. 74).  
Categorical data will be presented as simple or stacked bar charts where the height of the 
bar or bar segment, respectively, represents the percent of subjects in a particular 
category (e.g., see Gender, Race, and NYHA Class in [[Figure DEMO-1, p. 28]]).  
Continuous data will be presented as boxplots where the bottom whisker, bottom edge of 
the box, horizontal line through the box, top edge of the box, and top whisker indicate the 
5th, 25th (Q1), 50th (median), 75th (Q3), and 95th percentiles of the data, respectively, 
and a plotting symbol indicates the mean (e.g., see Age and Left Ventricular Ejection 
Fraction in [[Figure DEMO-1, p.28]]).  
Time-to-event data will be presented as Kaplan-Meier plots of cumulative incidence 
(e.g., [[Figure ENDPT-3, p. 71, top panel]]). In the Closed Session Reports, treatment 
comparisons for time-to-event analyses across different endpoints or for a single 
endpoint across different subgroups will be presented as forest plots showing point 
estimates and 95% confidence intervals (CIs) for hazard ratios (HRs), as in [[Figure 
ENDPT-4, p. 73]].  
A section of Supporting Material [[p. 74]] will contain back-up tables for the graphical 
displays of the previous chapters.  These tables will be cross-referenced to and from the 
corresponding graphical pages.  
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13.3.5. 
P-values  
In the closed session report, p-values for treatment comparisons will be provided for most 
post-baseline analyses.  These p-values should be viewed as screening tools, rather than 
formal hypothesis tests, as no adjustment will be made for multiple tests performed.  
Given the large number of tests to be considered, it would be expected that a number of 
p-values will appear statistically significant (<0.05) simply by chance.  
Except where otherwise noted, p-value calculations for continuous or ordered categorical 
data will use the nonparametric Wilcoxon-rank sum test (or Kruskal-Wallis test as 
appropriate), p-values for dichotomous and unordered categorical data will use Pearson's 
chi-square test without continuity correction, and p-values for time-to-event data will use 
a log-rank test.  
13.3.6. 
Use of Listings when Data Are Limited  
The study is expected to enroll 105 patients in the initial treatment arms, but early IDMC 
reports may include displays incorporating limited data on a small number of randomized 
patients. The detailed table of contents below and the Sample Report companion to this 
document assume a sufficient amount of data to support the use of graphical and tabular 
summaries. However, for initial reports where data for some displays are very limited, 
listings may be more appropriate and useful. SDAC will exercise its judgment in its use 
of graphics and tables versus listings in initial reports. On an ongoing basis, the IDMC, in 
consultation with SDAC, will evaluate the relative suitability of listings alone, summaries 
supplemented by listings, and summaries alone to communicate the results of interim 
analyses, and SDAC will adapt its reporting accordingly.  
13.3.7. 
Considerations for Analysis of Interim Data  
IDMC reports will be based on data from interim snapshots of the study database and 
other interim sources of data.  These sources are likely to include so-called “dirty” data: 
records that are incomplete, inconsistent, entered in error, not yet adjudicated or coded, 
and otherwise under query.  As a general approach, SDAC will include all available data 
in interim analyses, implementing reasonable conventions to resolve inconsistencies and 
handle incomplete records while utilizing statistical approaches that are robust in the face 
of errors.  
Detailed conventions for handling dirty data will be documented in the introductory 
material of IDMC reports, but general approaches will include:  
• 
Removing implausible or impossible values or assuming an appropriate unit 
conversion (e.g., height of 180 inches)  
• 
Using simple hierarchical definitions for potentially contradictory sources of 
information (e.g., calculating a death date using the adjudicated result if available 
and falling back on dates included in the clinical endpoint dataset, from fatal 
adverse event records in the adverse event dataset, etc.)  
• 
Presenting uncoded adverse events (AEs) in a separate category using the 
investigator-supplied verbatim term in tables and listings  
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• 
Completing partial dates using a sensible algorithm (e.g., middle of month if day 
is missing; middle of year if day and month are missing; with appropriate 
truncation for dates known or likely to be postrandomization)  
• 
Use of statistical techniques that are robust in the face of gross errors such as use 
of quantile-based descriptive statistics (medians, quartiles, and 5th and 95th 
percentiles) and non-parametric tests (Wilcoxon)  
13.4. 
PROPOSED DETAILED TABLE OF CONTENTS  
The list below represents the proposed content for the Closed Session Report.  The Open 
Session Report will have similar content (with analyses for randomized trials performed 
in aggregate only without respect to treatment group) but will exclude certain analyses as 
indicated above.  
In the following, references are given to representative examples of content in the Sample 
Report, though analyses in actual reports may be presented in a different form (e.g., 
listings in place of summaries where data are limited). Example graphics are presented 
with two treatment groups, though graphics for GSK 205801 may be modified to include 
three or more contrasts as applicable (see Sample Report, Chapter A3, p. 127).  
13.4.1. 
Accrual and Study Status  
[See the Sample Report Chapter 1 for illustrative examples.]  
• 
Subject accrual over time by treatment arm (line plot, with bar graph by month) 
[[Figure ACCR-1, p. 18]]  
• 
Site accrual over time (line plot, with bar graph by month) [[Figure ACCR-2, p. 
19]]  
• 
Geographic distribution of randomized subjects and randomizing sites (bar graph, 
table) [[Figures ACCR3-4, pp. 20-21]]  
• 
Accrual by stratification factors (squamous vs non-squamous, 1st vs 2nd line of 
PD(L) 1 therapy) (bar graph)  
• 
Subject treatment status, and reasons for IP discontinuation (bar graphs) [[Figure 
STAT-1, p. 23]]  
• 
Subject study/completion status, and reasons for early study termination (bar 
graphs) [[Figure STAT-1, p.  
23]]  
• 
Protocol violation/deviations (listing)  
13.4.2. 
Baseline Characteristics  
[See the Sample Report Chapter 2 for illustrative examples.]  
• 
Demographics [age, gender, race, ethnicity] (boxplot, bar graphs) [[Figure 
DEMO-1, p. 28]]  
• 
Medical history (bar graph) [[Figure MDHX-1, p. 29]]  
• 
Concomitant medication use at baseline by coded category (table)  
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• 
Vital signs [temperature, pulse rate, respiratory rate, blood pressure] (boxplots) 
[[Figure VITB-1, p. 30]]  
• 
Physical measurements [height, weight, BMI] (boxplots) [[Figure VITB-1, p. 30]]  
• 
Baseline labs [[Figure LABB-1, p. 31]]   
13.4.3. 
Adverse Events  
  [See the Sample Report Chapter 3 for illustrative examples.] Serious adverse events:  
• 
Listing of deaths  
• 
Overview [any SAE, any SAE possibly related to study treatment, SAE leading to 
IP and/or study discontinuation, any fatal SAE] (bar graph) [[Figure SAE-1, p. 
33]]  
• 
Tabulation by SOC and High Level Term/Preferred Term (tables) [[Table 
SAETAB, p. 35]]  
• 
Listing of SAEs by subject (listing showing treatment group, subject ID, sex, age, 
country, randomization date, start and end day of event relative to randomization 
and treatment periods, MedDRA preferred  
term, action taken with respect to study drug) [[Figure AELISTING-1, p. 38]]  
Adverse events (whether serious or non-serious) leading to study drug discontinuation:  
• 
Overview (AEs leading to treatment discontinuation, study withdrawal, dose 
interruptions/reductions) (bar graph) [[Figure AE-1, p. 39]]  
• 
AE frequency by MedDRA SOC (stacked bars indicating max severity) [[Figure 
AE-2, p. 40]]  
• 
Most common AEs [by MedDRA PT/HLT] (stacked bars indicating max severity) 
[[Figure AE-3, p. 41]]  
• 
AEs with a nominally significant treatment difference (closed session only) 
[[Figure AE-4, p. 42]]  
• 
Tabulation of by SOC and PT/HLT (tables) [[Table AETAB, p. 43]  
Immune-related adverse events (irAEs)  
• 
irAEs as described in Section 7.2.1.1 and Table 8 (p. 41) of the Study Protocol 
(bar graphs) [[similar to Figure AE-2, p.40]]  
Adverse events of Special Interest (bar graphs) [[similar to Figure AE-2, p. 40]]  
• 
Subclasses of AEs provided to SDAC by GSK in AESI LISTING: o Pneumonitis, 
colitis, hepatitis, endocrinopathies, nephritis and renal function, skin adverse 
reactions, other immune-mediated adverse events (see AESI LISTING for full 
specifications)  
• 
Infusion-related reactions o (see AESI LISTING for full specifications)  
  
13.4.4. 
Central Laboratory Measures  
Open session reports will omit all laboratory results that may unblind the study sponsor; 
SDAC will communicate with GSK to establish any lab parameters to be omitted.  
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[See the Sample Report Chapter 4 for 
illustrative examples.] General laboratory 
presentation:  
• 
Summary page for each set of tests showing the percent above and/or below 
thresholds, as appropriate, for each test in the set (bar charts, with stacked bars 
for categorical assessments and for LFT elevations categorized by multiples of 
ULN) [[Figure LFTABN-1, p.49]]  
• 
Each laboratory measure by scheduled visit [[Figure LFT-1, p. 50]]: o For most 
lab tests, multiple panels: measurements at each visit (boxplot), change from 
baseline (boxplot), percent of subjects above and/or below thresholds (ULN, 
LLN, or other clinically defined values of concern) at each visit (bar graph)  
o For ordered categorical results (e.g., some urinalysis assessments): 
stacked bars indicating the percent of subjects in each category at each visit 
o Categories of laboratory measures displayed using above presentation:  
▪ 
Hematology  
▪ 
Clinical chemistry  
▪ 
Urinalysis  
  
13.4.5. 
Other Follow-up Measures  
[See the Sample Report Chapter 5 for illustrative examples.]  
• 
Vital signs [body temperature, pulse rate, respiratory rate, systolic and diastolic 
blood pressure] (box plots by visit, with change from baseline) [[Figure VIT-1, p. 
60]]  
• 
Physical measurements [weight, BMI] (boxplots) [[Figure VIT-3, p. 62]]  
• 
Physical exam [clinically significant changes since previous visit] (listing)  
• 
ECG interpretation (bar graph by visit) [[Figure ECG-1, p. 63]]  
• 
ECG data [QT, QTcF RR, GR, PR, QRS] (box plots by visit, with change from 
baseline) [[Figure ECG-2, p. 64]]  
  
13.4.6. 
Efficacy and Interim Analyses  
 As specified in Section 3.1 of the Study RAP, formal interim analyses will be conducted 
by SDAC and presented to the IDMC in closed session. These analyses will be triggered 
after approximately 45 total observed events in the combined experimental and SoC 
arms, with a minimum of 18 events in the experimental arm.   
  
[See the Sample Report Chapter 6, Study Endpoints, pp. 69-72 for 
illustrative examples] Primary Efficacy Parameters:  
• 
Predictive probability of Phase III study success for each treatment arm as 
described in Section 10.5.1 of the Study Protocol — if triggered by events.   
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Key secondary Efficacy Parameters  
• 
All-cause mortality (overall survival) (Cumulative mortality, forest plot) 
[[ENDPT-3, p. 71; ENDPT-4, p.72]]  
• 
Kaplan-Meier estimates of milestone survival rates at 12 and 18 months (forest 
plot) [[similar to ENDPT4, p. 72]]  
 
Note: Shells can be found here: 
https://biostat.wiscweb.wisc.edu/wp-
content/uploads/sites/1008/2019/05/Sample_Report_Closed_20160920.pdf  
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