A Global, Molecular Disease Characterization Initiative (MDCI) in Oncology Clinical Trials
Phase: PHASE2
Conditions: Lung Cancer, Non-Small Cell, Neoplasms
Sponsor: GlaxoSmithKline

                                                    Protocol 
 
 
Study ID: 213299 
 
Official Title of Study: A Global, Molecular Disease Characterization Initiative 
(MDCI) in Oncology Clinical Trials 
 
Date of Document: 25 Oct 2021 
 
NCT number: NCT04772053 
 
 
 
 
 

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TITLE PAGE 
Protocol Title: A Global, Molecular Disease Characterization Initiative (MDCI) in 
Oncology Clinical Trials 
Protocol Number: 213299/ Amendment 03 
Compound Number or Name: 
None 
Study Phase: Phase I/Phase II 
Short Title: Molecular Disease Characterization Initiative (MDCI) 
Sponsor Name and Legal Registered Address:  
GlaxoSmithKline Research & Development Limited 
980 Great West Road 
Brentford 
Middlesex, TW8 9GS 
UK 
Medical Monitor Name and Contact Information  
May be found in the Study Reference Manual (SRM). 
Regulatory Agency Identifying Number(s):  
IND: N/A 
EudraCT:  N/A 
NCT: N/A 
WHO: N/A 
EUDAMED N/A 
 
Approval Date: 25-OCT-2021 
 
 
©2021 GSK group of companies or its licensor. All rights reserved. Unauthorized 
copying or use of this information is prohibited. 

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SPONSOR SIGNATORY: 
Protocol Title: A Global, Molecular Disease Characterization Initiative (MDCI) in 
Oncology Clinical Trials 
Protocol Number: 213299/ Amendment 03  
Compound Number 
or Name: 
  
None 
 
 
 
 
 
 
 
 
Hesham A. Abdullah, MD, MSc, RAC 
Senior Vice President, Head of Clinical Development, 
Oncology 
Oncology R&D, GSK 
 
Date 
 
The signed page is a separate document. 
 
 
 
 
Medical Monitor Name and Contact Information can be found in the Study 
Reference Manual 
 

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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
List dates of original protocol and all amendments in reverse chronological order. 
Document 
Date 
DNG or TMF Number 
Amendment 03 
25-OCT-2021 
TMF-13855541 
Amendment 02 
25-NOV-2020 
2019N418193_02 
Amendment 01 
15-JUN-2020 
2019N418193_01 
Original Protocol 
09-MAR-2020 
2019N418193_00 
 
Amendment 03 25-OCT-2021  
This amendment is considered to be non-substantial based on the criteria set forth in 
Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of 
the European Union because it neither significantly impacts the safety or 
physical/mental integrity of participants nor the scientific value of the study. 
Overall Rationale for the Amendment: The overall rationale for this amendment is to 
clarify requirements on data collection and data entry, remove ICOS and epigenetic 
language, included the option for sites to send FFPE slides. Provided guidance on 
historical scans and image-guided biopsy. Updated the Introduction section to reflect 
GSK Oncology clinical trials and development updates. Schedule of activities table was 
updated to reflect changes made to the data collection and data entry requirements as well 
as provided guidance for combining Visit 1 and Visit 2 and option to have Visit 3 as a 
telehealth/phone visit. Included age requirement under inclusion criteria. Contraceptive 
use requirement for men was removed from inclusion criteria. Details on rationale are 
provided in the Table below. 
 
 

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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 1.1 
Synopsis 
Removal of ICOS IHC 
requirement 
To align with removal of ICOS studies 
from MDCI 
Section 1.1 
Synopsis 
Added language for combining 
Visit 1 and Visit 2 as an option 
To provide guidance on option to 
combine Visit 1 and Visit 2  
Section 1.2 
Schema and 
Section 4.1 Overall 
Design (Figure 2)  
Updated study schema design 
To align with updates to combine Visit 
1 and Visits 2 as an option; allow for 
Visit 3 to be telehealth as an option; 
and provide flexibility to accommodate 
the sites for scheduling Visit 1 and 2  
Section 1.3 
Schedule of 
Activities (SoA) 
Updated SoA Table 1: 
-Remove alcohol history 
requirement 
-Added radiation therapy under 
footnote 2 to be collected as part 
of medical history  
-Added footnotes to clarify 
option to combine Visit 1 and 
Visit 2; Visit 3 option for 
telehealth 
-Included footnote to allow 
transfer of HLA results from 
another GSK study to be used in 
MDCI 
-Removed vital signs from Visit 3 
-Removed requirement for 
height and respiration rate   
-Removed requirement to collect 
prior and current anti-cancer 
therapies from Visit 3 
-Added requirement to record 
weight at Visit 2 
-Added haematology and 
coagulation labs to be collected 
at Visit 2; added footnote to 
clarify Visit 2 labs should be 
performed as close as possible 
as biopsy assessment where 
applicable 
To align with changes in data 
collection and data entry requirements. 
Changes made to reflect feedback 
from sites.   

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Section # and 
Name 
Description of Change 
Brief Rationale 
-Added footnote to clarify that 
FFPE slides (details in SRM) 
can be sent instead of tissue 
block as per institutional 
guidance/policy  
-Added review of actionable 
results at Visit 3 
- Added pre-study scans related 
to archived tumor specimen to 
the SoA to clarify scan 
requirements 
- Clarified that ECG should be 
done at baseline during Visit 1 
and should be recorded in 
eCRF; removed ECG 
requirement from Visit 2 
-Added footnote that if an ECG 
is done within 2 weeks of Visit 1, 
it can be used for this study, if 
the patient has not had any 
cardiac event. 
-Added footnotes to clarify 
withdrawal visit requirements. 
-For infectious disease 
biomarkers added footnote to 
include a window: Local test 
results are acceptable, if 
generated within 4 weeks from 
Visit 1. 
Section 2.2 
Background 
Removed ICOS language  
To reflect GSK Oncology clinical trials 
and development updates 
Section 2.2 
Background 
Added PVRIG, CD96 and TIGIT 
language  
To reflect GSK Oncology clinical trials 
and development updates 
Section 2.2 
Background  
Removed epigenetics language  
To reflect GSK Oncology clinical trials 
and development updates 
Section 5.1 
Inclusion Criteria  
Added language to clarify that 
FFPE slides can be sent instead 
of tissue block as per 
institutional guidance/policy  
To clarify option for tissue sample 
being submitted for this study 

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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 5.1 
Inclusion Criteria 
Removed contraceptive use 
requirement for men  
To align with IRB and safety feedback 
as this is not required as MDCI is a 
non-therapeutic study 
Section 5.1 
Inclusion Criteria 
Added age requirement for 
eligibility under study 
To align with requirement for age of 
consent  
Section 7.2 Tumor 
Imaging  
Added language on image-
guided biopsy under Section 
7.2.3 (Imaging from Image-
Guided Biopsy) and historical 
scans under Section 7.2.4 
(follow up imaging) 
To provide guidance on historical 
scans and image-guided biopsy 
Section 7.4.3 
Electrocardiograms 
Added language to ECG results 
requirements 
To align with requirement of 
performing ECG and recording results 
into eCRF, only at baseline during Visit 
1.  
Section 8.2 
Sample Size 
Determination  
The following sentence was 
added: 
Expected to enroll 400 
participants in this study 
To include the expected number of 
participants to be enrolled in the study  
Section 8.3 
Population for 
analyses 
Population for analyses 
definition was updated  
To clarify the populations that will be 
included in the analyses  
Section 9.3.2 
Updated definition of SAE to: 
An SAE is defined as any 
untoward medical occurrence 
that, at any dose, meets one or 
more of the criteria listed 
To align with updates from the global 
SAE template 
Section 9.3.4 
Reporting of SAE 
to GSK 
Removal of bullet point for 
requirement to verify relationship 
of SAE to IP within 72 hours  
To align with updates from the global 
SAE template  
Section 10 
References 
New references were added and 
some references were updated 
or deleted 
Updated references to align with 
changes in the main text 

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TABLE OF CONTENTS 
PAGE 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 3 
1. 
PROTOCOL SUMMARY ........................................................................................ 10 
1.1. 
Synopsis ..................................................................................................... 10 
1.2. 
Schema ...................................................................................................... 15 
1.3. 
Schedule of Activities (SoA) ........................................................................ 16 
2. 
INTRODUCTION .................................................................................................... 19 
2.1. 
Study Rationale .......................................................................................... 19 
2.2. 
Background ................................................................................................ 21 
2.2.1. 
Cancer immunotherapies ............................................................. 22 
2.2.2. 
Cell and Gene Therapy (TCR engineered adoptive T-cell 
therapy targeting NY-ESO-1/LAGE-1a) ....................................... 24 
2.2.2.1. 
Background for Current GSK TCR-T cells .................. 25 
2.2.2.2. 
Background for HLA & Screening ............................... 26 
2.2.3. 
Synthetic Lethality Therapy .......................................................... 26 
2.3. 
Benefit/Risk Assessment ............................................................................ 27 
2.3.1. 
Risk Assessment ......................................................................... 27 
2.3.2. 
Benefit Assessment ..................................................................... 29 
2.3.3. 
Overall Benefit: Risk Conclusion .................................................. 29 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 30 
4. 
STUDY DESIGN .................................................................................................... 31 
4.1. 
Overall Design ............................................................................................ 31 
4.2. 
End of Study Definition ............................................................................... 34 
5. 
STUDY POPULATION ........................................................................................... 34 
5.1. 
Inclusion Criteria ......................................................................................... 34 
5.2. 
Exclusion Criteria ........................................................................................ 36 
5.3. 
Screen Failures........................................................................................... 36 
6. 
STUDY INTERVENTION ........................................................................................ 37 
6.1. 
Participant Discontinuation/Withdrawal from the Study ............................... 37 
6.2. 
Lost to Follow Up ........................................................................................ 37 
7. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 38 
7.1. 
Gather Share Know Participant Hub ........................................................... 38 
7.2. 
Tumor Imaging............................................................................................ 39 
7.2.1. 
Imaging Related to Archived Tumor Sample ................................ 39 
7.2.2. 
Visit 2 Imaging ............................................................................. 39 
7.2.3. 
Imaging from Image-Guided Biopsy ............................................. 40 
7.2.4. 
Follow Up Imaging ....................................................................... 41 
7.3. 
Efficacy Assessments ................................................................................. 41 
7.4. 
Safety Assessments ................................................................................... 41 
7.4.1. 
Physical Examinations ................................................................. 41 
7.4.2. 
Vital Signs .................................................................................... 41 
7.4.3. 
Electrocardiograms ...................................................................... 42 
7.4.4. 
Clinical Safety Laboratory Assessments ...................................... 42 

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8  
 
7. 5.  
A d v er s e E v e nt s a n d S eri o u s A d v er s e E v e nt s  ............................................. 4 3  
7. 5. 1.  
Ti m e P eri o d a n d Fr e q u e n c y f or C oll e cti n g A E a n d S A E 
I nf or m ati o n ................................................................................... 4 3  
7. 5. 2.  
M et h o d of D et e cti n g A E s a n d S A E s  ............................................. 4 3  
7. 5. 3.  
F oll o w -u p of A E s a n d S A E s  ......................................................... 4 4  
7. 5. 4.  
R e g ul at or y R e p orti n g R e q uir e m e nt s f or S A E s  ............................. 4 4  
7. 5. 5.  
Pr e g n a n c y  ................................................................................... 4 4  
7. 5. 6.  
D e at h E v e nt s  ............................................................................... 4 4  
8.  
S T A TI S TI C A L C O N SI D E R A TI O N S  ........................................................................ 4 9  
8. 1.  
St ati sti c al H y p ot h e s e s ................................................................................. 4 9  
8. 2.  
S a m pl e Si z e D et er mi n ati o n  ........................................................................ 4 9  
8. 3.  
P o p ul ati o n s f or A n al y s e s  ............................................................................ 4 9  
8. 4.  
St ati sti c al A n al y s e s  ..................................................................................... 4 9  
8. 4. 1.  
S af et y A n al y s e( s)  ......................................................................... 5 0  
8. 4. 2.  
Ot h er A n al y s e( s)  .......................................................................... 5 0  
8. 5.  
I nt eri m A n al y s e s ......................................................................................... 5 1  
8. 6.  
Tr a n sl a ti o n al R e s e ar c h C o m mitt e e ............................................................. 5 1  
8. 7.  
Li mit ati o n s  .................................................................................................. 5 1  
9.  
S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L  
C O N SI D E R A TI O N S  ............................................................................................... 5 2  
9. 1.  
A p p e n di x 1: R e g ul at or y, Et hi c al, a n d St u d y O v er si g ht 
C o n si d er ati o n s  ............................................................................................ 5 2  
9. 1. 1.  
R e g ul at or y a n d Et hi c al C o n si d er ati o n s  ........................................ 5 2  
9. 1. 2.  
Fi n a n ci al Di s cl o s ur e  ..................................................................... 5 2  
9. 1. 3.  
I nf or m e d C o n s e nt Pr o c e s s .......................................................... 5 3  
9. 1. 4.  
D at a Pr ot e cti o n  ............................................................................ 5 3  
9. 1. 5.  
C o m mitt e e s Str u ct ur e  .................................................................. 5 4  
9. 1. 6.  
Di s s e mi n ati o n of Cli ni c al St u d y D at a  ........................................... 5 4  
9. 1. 7.  
D at a Q u alit y A s s ur a n c e  ............................................................... 5 4  
9. 1. 8.  
S o ur c e D o c u m e nt s  ...................................................................... 5 5  
9. 1. 9.  
St u d y a n d Sit e St art a n d Cl o s ur e  ................................................. 5 5  
9. 1. 1 0.  
P u bli c ati o n P oli c y  ......................................................................... 5 6  
9. 2.  
A p p e n di x 2: Cli ni c al L a b or at or y T e st s  ......................................................... 5 7  
9. 3.  
A p p e n di x 3: A d v er s e E v e nt s: D efi niti o n s a n d Pr o c e d ur e s f or 
R e c or di n g, E v al u ati n g, F oll o w -u p, a n d R e p orti n g  ....................................... 5 8  
9. 3. 1.  
D efi niti o n of A E  ............................................................................ 5 8  
9. 3. 2.  
D efi niti o n of S A E  .......................................................................... 5 9  
9. 3. 3.  
R e c or di n g a n d F oll o w -U p of A E a n d S A E  .................................... 6 0  
9. 3. 4.  
R e p orti n g of S A E t o G S K  ............................................................. 6 2  
9. 4.  
A p p e n di x 4: C o ntr a c e pti v e G ui d a n c e a n d C oll e cti o n of Pr e g n a n c y 
I nf or m ati o n .................................................................................................. 6 3  
9. 4. 1.  
D efi niti o n s:  ................................................................................... 6 3  
9. 4. 2.  
C o ntr a c e pti o n G ui d a n c e:  ............................................................. 6 4  
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9.4.3. 
Collection of Pregnancy Information ............................................ 65 
9.5. 
Appendix 5: Abbreviations and Trademarks ................................................ 66 
9.6. 
Appendix 6: Protocol Amendment History ................................................... 68 
10. REFERENCES ....................................................................................................... 71 
 
 
 

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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: A Global, Molecular Disease Characterization Initiative (MDCI) in 
Oncology Clinical trials  
Short Title: Molecular Disease Characterization Initiative (MDCI) 
Rationale: 
It is estimated that over 600,000 people will die from cancer in 2020 [American Cancer 
Society (ACS), 2020]; advancement is needed in further understanding biological 
mechanisms underpinning clinical outcomes and identification of novel pathways 
contributing to oncogenesis or treatment resistance.  
The aim of this protocol is to leverage science and data, by comprehensively analyzing 
and compiling data from cancer patients’ disease, in an effort to reduce time-to-
treatment for patients, while learning of potentially novel therapeutic regimens, to 
address these two unmet needs for cancer patients; both of which lend to reducing the 
projections of cancer deaths. MDCI will accomplish this by looking at a patient’s tumor 
specimen by validated clinical immunohistochemistry(IHC) assays coupled with whole 
exome and whole transcriptome sequencing. Based on IHC data, as well as previous 
medical history, all potential clinical trial options are returned; reducing time-to-
treatment by supporting screening against all trial options, instead of one at a time. 
Sequencing data collected will allow researchers to correlate to outcome, potentially 
discovering novel targets/pathways, as well as co-expression of biomarkers; allowing for 
data-driven, novel treatment regimens. 
Oncology, as a field, is moving away from ‘universal treatment’ and is evolving to a 
‘precision medicine’ paradigm with therapy tailored to individual disease profile. The use 
of a precision medicine approach in oncology, however, also requires multiplex testing of 
tumor specimens at diagnosis and relapse, which presents challenges to timely evaluation 
thereby reducing the probability of a patient to participate in any one clinical trial. For 
oncology patients, the urgent need for timely treatment does not allow for a sequential, 
complex, and time-consuming process that is inherent in the tandem, focused screening 
for each individual clinical trial. Moreover, we have learned that determining a single 
analyte alone does not always correlate to clinical benefit [Blons, 2019]. While 
evaluating specimens for treatments available today, it is critical to understand, as well, 
the heterogeneity of a patient’s disease and what molecular signatures may be present 
that do not have a targeted regimen, if we hope to impact cancer patient 
response/outcomes. Design and Data from trials such as the Lung-MAP study further 
emphasize this approach; ‘as we begin to target less common genomic and 
immunotherapy subtypes, centrally coordinated clinical trial designs such as Lung-MAP 
are necessary to rapidly deliver effective therapies to patients, whereas also maximizing 
the quality of research data obtained’[Lam, 2018].  

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In this study, tumor specimens will be comprehensively evaluated both for patient-
selection biomarkers relevant to the therapies within the GSK oncology clinical trials, as 
well as towards identifying novel targets.   The data generated from validated clinical 
assays used in GSK investigational study protocols will be made available to help inform 
investigators and patients of clinical trials they may be best suited for. The results of this 
analysis will be shared with the investigator first, before being available to the patient 
(where not prohibited by local regulations), through individual portals (the investigator 
portal through the GSK  sequencing partner; the patient portal, named ‘Gather Share 
Know’,  is established by GSK in collaboration with an external partner). This study will 
involve many sites, located over a wide geographic footprint, with the intent of 
significantly expanding the opportunities for identifying participants and simplifying the 
screening process into clinical trials. 
Expected Impact of MDCI Model 
MDCI aims to create a platform to accelerate the availability of new therapeutic options 
for patients and increase participation in precision medicine clinical trials, while building 
a scientific database (GSK Clinical Science Database) to facilitate the investigation of 
biological mechanisms underpinning clinical outcomes in oncology. 
This protocol design is expected to benefit patients, oncology healthcare providers, and 
clinical research: 
• Patient:  
o Providing potential GSK trial options at the first testing timepoint; 
permitting efficient navigation of available trial options without the need 
for subsequent testing to screen for additional trials.  
o Returning a subset of data from validated clinical assays in a plain 
language summary, in real-time, as well as information to participants on 
MDCI study visits and what to expect through participant hub. 
• Physician:  
o Providing a comprehensive view of all genetic and protein data, on 
patients’ disease status   
o Reducing the need for repetitive screening in order to consider enrolling in 
multiple trials.  
• Oncology Research:  
o Developing a GSK Clinical Science Database that may facilitate 
innovation, through further understanding of mechanisms of action or 
resistance leading to the identification of novel targets and potential 
combination approaches.  
o Leveraging artificial intelligence/machine learning (AI/ML) for algorithm 
builds of the data collected 
 

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O bjecti ves a n d E n d p oi nts:  
O bjecti ves  
E n d p oi nts  
Pri mar y  
Pri mar y  
•  
T o 
e val uate 
m olec ular 
a n d 
i m m u n ol o gical 
pr ofile 
of t u m or 
a n d 
peri p heral 
bl o o d 
of 
all 
e nr olle d 
partici pa nts, acr oss i n dicati o ns a n d wit hi n 
t u m or s u bsets ( B uil di n g a G S K Cli nical 
Scie nce D ata bas e f or t u m or pr ofili n g a n d 
c orrel ati ve st u dies)  
 
•  Pr ofile of patie nt s pecific selecti o n 
bi o mar kers tar get e d b y t hera p e utics 
wit h t he G S K o nc ol o g y pi peli ne, as 
well as ot her
bi o mar kers as 
detaile d i n t he st u d y refere nce ma n ual 
( S R M). 
 
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O ver all Desi g n:  
T his is a m ultice nter st u d y, e nr olli n g partici pa nts wit h a d va nce d/ met astatic disease f or 
t he p ur p ose of bi os peci me n c ollecti o n (t u m or tiss ue a n d bl o o d sa m ples) f or br oa d 
m olec ular pr ofili n g a n d e x a mi ni n g t he e x pre ssi o n of s pecific a nti ge ns (e. g. N Y-E S O -1, 
L A G E -1a), i m m u ne mar kers (e. g. P D -L 1), t u m or i m m u ne i nfiltrates, differe ntiall y 
e x presse d ge nes, a n d H u ma n Le u k oc yte A nti ge n ( H L A) ge n ot y p e.  Res ults fr o m 
vali date d cli nical assa ys will s u p p ort t he referral of eli gi ble p artici pa nts i nt o a n 
a p pr o priate G S K Cli nical trial. T hese res ults, paire d wit h cli nical & se q u e nci n g res ults, 
will facilitate t he b uil di n g of a scie ntific d ata bas e ( G S K Cli nical Scie nce Data base) 
per mitti n g i n vesti gati o n of mec ha nis ms u n der pi n ni n g t he acti vit y of tar get e d a ge nts, 
resista nce t o t hera p y, a n d c o n d ucti n g ot h er c orrelati ve a nal ys es. 
•  Partici pa nts w h o are H L A -A * 0 2: 0 1, H L A -A * 0 2: 0 5, H L A -A * 0 2: 0 6  p ositi ve a n d 
w h ose t u m or tiss ue e x presses  N Y -E S O -1 a n d/ or L A G E -1a b y a vali date d assa y 
( base d o n rele va nt cli nical c ut-off d etaile d i n S R M & ot her i ncl usi o n/e xcl usi o n 
criteria) m a y be referre d t o G S K 3 3 7 7 7 9 4, G S K 3 8 4 5 0 9 7, &/ or G S K 3 9 0 1 9 6 1 
cli nical trial(s)  
•  Partici pa nts w h ose t u m or tiss ue is p ositi ve b y v ali date d P D L -1 ( S P 2 6 3) I H C 
( base d o n rele va nt cli nical c ut-off d etaile d i n S R M & ot her i ncl usi o n/e xcl usi o n 
criteria) m a y be referre d t o G S K 3 3 5 9 6 0 9  cli nical trial(s).  
•  Base d o n B R C A 1 or 2 m utati o n, H o m ol o g o us Rec o m bi nati o n Defici e nc y ( H R D) 
&/ or P D L -1( S P 2 6 3) t u m or stat us, partici pa nts ma y be referre d t o Nira p ari b 
trial(s). 
Vali date d cli nical bi o mar ker data will be ret ur ne d t o t he p h ysicia n, as well as a s u bset t o 
t he partici pa nt, t hr o u g h i n di vi d ual p ortal s yste ms. T his st u d y will als o utilize t u m or a n d 
bl o o d sa m ples f or
researc h p ur p oses, i ncl u di ng p ote ntial bi o mar ker, 
c o m pa ni o n dia g n ostic, a n d i n vesti gati o nal ge n etic researc h.  
It is a ntici pate d t hat t his m olec ular diseas e c haracterizati o n pr ot oc ol will s u p p ort 
scree ni n g f or G S K O nc ol o g y trials, o utli ne d wit hi n S R M. 
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Disclosure Statement: This is a single arm interventional molecular analysis study with 
no administration of investigational product and no masking. 
Number of Participants: Approximately 400 participants will be enrolled into this 
molecular analysis study. 
Study Groups and Duration: 
Enrolled participants will be followed in two groups; (a) those enrolled onto a GSK 
clinical trial following Visit 3 and (b) those followed longitudinally, with disease re-
analyzed at progression (Schedule of Activities Table 2).  The total number of 
participants anticipated for this study is  400.  Following consent, participants will have 
three initial study visits (further details on visits can be found in Schedule of Activities 
(SoA) and Section 4.1).  
• Visit 1: Informed consent, review of medical history, targeted physical exam,  
information on Gather Share Know 
• Visit 2: Biospecimen collection (e.g. tumor sample, blood ), imaging  
• Visit 3: Review results & trial matches with Physician, decide treatment 
options/treatment trial. 
Note: Visit 1 and 2 may be combined, if appropriate, to reduce individual study visits. 
In the case that Visit 1 and 2 are combined, all corresponding samples must be 
collected per the SoA at this visit. In this scenario, following consent, all eligibility 
criteria should be confirmed prior to taking any Visit 2 assessments. 
If a patient does not enroll onto a GSK study, or any other investigational study, the 
patient may remain under MDCI and be followed as per assessments on SoA Table 2. 
Duration: It is expected that a majority of patients complete Visit 1 through Visit 3 
in <8 weeks; Participants who are followed longitudinally (SoA Table 2) may be 
followed for 2 years. 
The study protocol will remain open until all designated GSK-sponsored impacted 
clinical trials (outlined in SRM) are closed to enrolment & all participants have 
completed this study or at the discretion of GSK. 
 
Data Monitoring or Other Committee:  
Study 213299 Translational Research Committee 
This committee is composed of both internal and external disease-area experts. The 
objective of the Translational Research Committee for Study 213299 is to consult on trial 
design, development, and implementation of MDCI. Interim data will be reviewed to 
facilitate these efforts. 
 

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1.2. 
Schema 
  
 
Footnotes: 1MDCI will be an optional protocol under select GSK oncology protocols; 2In the case that Visit 1 and 2 are combined, all corresponding 
samples must be collected per the SoA (Section 1.3 Table 1) at this visit and after eligibility is confirmed; 3Subset of data to be shared on Gather Share 
Know; 4Patient’s molecular profile and medical history will be compared against the eligibility criteria of select GSK oncology protocols to identify 
potential trial options; 5Visit 3 may occur remotely via telehealth/phone visit (optional). 

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1.3. 
Schedule of Activities (SoA) 
Table 1 
Schedule of Activities (SoA) for Study 213299 
Procedures 
Visit 
1 
Visit 2(1) 
Visit 
3/Withdrawal(1) 
Withdrawal 
(17) 
 
Informed consent(15) 
X 
 
 
 
Footnotes: 
1. 
Visit 2 should occur within 4 weeks of Visit 1 (dependent on 
assessment scheduling) or can be combined with Visit 1 
assessments, if applicable. In the case that Visit 1 and 2 are 
combined, all corresponding samples must be collected per the 
SoA at this visit. Visit 3 is a Withdrawal visit for patients not 
continuing to be monitored under MDCI (Table 2) and may occur 
remotely via telehealth/phone visit (refer to SRM for details). 
2. 
Past /current medical conditions, anti-cancer therapies, radiation 
therapy, and cancer-related prior surgical history will be 
collected for all participants.  
3. 
Woman of Childbearing Potential (WOCBP, see Appendix 4) 
must have a negative urine or serum pregnancy test a) at study 
start to be eligible for this study & b) prior to procedure(s) 
4. 
Includes HIV, HBV, HCV, HTLV, EBV, CMV, and syphilis 
(spirochete bacterium).  Local test results are acceptable, if 
generated within 4 weeks from Visit 1. 
5. 
HLA sample – one blood sample (see Section 7.7.4). HLA 
results from another GSK study may be transferred to be used 
in MDCI (see SRM and Study Laboratory Manual for details). 
6. 
Liquid Biopsies – two blood samples (see Section 7.7.5)  
7. 
Genetics sample – one blood sample (see Section 7.6) 
8. 
Formalin-fixed, paraffin-embedded (FFPE) tumor block or fresh 
biopsy specimen, per Inclusion Criteria (see Section 5.1). 
Archival sample can be requested and sent after patient has 
consented. If an archival block cannot be sent as per 
Inclusion and exclusion criteria 
X 
 
 
 
Demography 
X 
 
 
 
Full physical examination 
X 
 
 
X 
Past /current medical conditions 
including Tobacco history and prior 
surgical history(2) 
X 
 
 
 
Disease History Form 
X 
 
 
 
Prior and Current anti-cancer 
therapies(2) 
X 
X 
 
X 
Prior and Current Medications 
X 
X 
X 
X 
Vitals(14) 
X 
X 
 
X 
Weight 
X 
X 
 
 
Disease Characteristics 
X 
 
 
  
Single 12-Lead ECG(16) 
X 
 
 
 
Pregnancy test(3) 
X 
X 
 
 
Hematology 
X 
X(18) 
 
 
Coagulation 
X 
X(18) 
 
 
Infectious Disease Markers(4) 
X 
 
 
 

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Procedures 
Visit 
1 
Visit 2(1) 
Visit 
3/Withdrawal(1) 
Withdrawal 
(17) 
 
ECOG 
X 
 
 
 
institutional guidance/policy, slides can be sent instead, refer to 
the SRM and Study Laboratory Manual for further details. 
9. 
For participants with archived tumor specimen: Imaging by 
CT/MRI conducted for tumor assessment within ±4 weeks of 
tumor biopsy will be collected. Images from image-guided 
biopsy procedures (if conducted) will also be collected. See 
Section 7.2. 
10. CT/MRI to assess tumor(s). Imaging visit window ±4 weeks (28 
days), or -4 weeks if fresh tissue biopsy is conducted at Visit 2. 
Imaging for standard of care tumor assessment may be used if it 
was acquired within 28 days and conforms to the protocol 
imaging requirements in Section 7.2.3. Images from image-
guided biopsy procedures (if conducted) will be collected.  
11. Following completion of informed consent, patients will be 
provided credentials to log into the Gather Share Know 
Participant hub (see Section 7.1) 
12. For those participants who are not eligible for a GSK clinical 
trial, please refer to Table 2 SoA 
13. SAEs assessed as related to study procedure(s) or lead to study 
withdrawal 
14. Blood Pressure, Pulse Rate, Temperature. If Visit 1 and 2 are 
combined, vital signs only need to be recorded once.  
15. Must be signed before any study specific assessments are 
performed.  
16. ECG to be performed at baseline during Visit 1 and result to be 
entered into eCRF. An ECG done within 2 weeks of Visit 1 is 
acceptable, if the patient has not had any cardiac event. 
17. Withdrawal Visit applicable only if participant withdraws from 
study prior to Visit 3. 
18. Visit 2 haematology and coagulation laboratory tests to be 
performed as close as possible to the biopsy assessment. 
HLA genotyping 
 
X(5) 
 
 
 
Liquid biopsy (blood)  
 
X(6) 
 
 
X 
Genetics sample  
 
X(7) 
 
 
 
Tumor specimen 
 
X (8) 
 
 
 
 
Pre-study scans related to archived 
tumor specimen 
X(9) 
 
 
 
Tumor Imaging 
 
X (10) 
 
 
Review of AEs and SAEs that are 
related to study procedure(s) or lead 
to study withdrawal(13) 
X 
X 
X 
X 
Gather Share Know Credentials 
X (11) 
 
 
 
Referral to intended GSK Treatment 
protocol 
 
 
 
X (12) 
 
Review of actionable results 
 
 
X 
 

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Table 2 
Schedule of Activities For Participants Ineligible for Treatment Trial 
Note: For those participants not eligible for a GSK treatment trial or other clinical trial, and who receive Standard of Care (SoC), disease 
will continue to be monitored under MDCI following Table 2 assessments: 
Procedures 
Q26W 
until 
W104 
Withdrawal/At 
Progression 
 
Visit Window 
4W 
4W 
 
Liquid Biopsy 
X 
X 
Footnotes: 
1. Subsequent treatment and the associated clinical outcomes of interest will be collected for 
participants who do not enroll in a treatment protocol. 
2. Survival follow up will be conducted for participants who do not enroll in a treatment 
protocol. 
3. If patient progresses while on Standard of Care (SoC), a tumor biopsy may be taken for 
re-analysis & potential referral to a treatment trial based on results. Image guidance 
preferred when feasible. Images from guidance procedure will be collected (see Section 
7.2.3). 
4. Any imaging for standard of care tumor assessment by CT, MRI, PET, nuclear medicine, 
Xray, or photography that was conducted will be collected. Visit window for imaging ±8 
weeks.  
5. Imaging for tumor assessment conducted within 4 weeks prior to biopsy will be collected. 
Imaging conducted after biopsy is not required to be collected. 
6. Blood Pressure, Pulse Rate and Temperature  
Tumor Specimen(3) 
 
X 
Tumor Imaging 
X(4) 
X(5) 
Vitals(6) 
X 
X 
Review of AEs and SAEs that are 
related to study procedure(s) or lead to study 
withdrawal 
X 
X 
Current anti-cancer therapies(1) 
X 
X 
Survival Follow up(2) 
 
 
X 
X 

T M F -1 3 8 5 5 5 4 1  
C O N FI D E N TI A L  
 
 
 
2 1 3 2 9 9  
 
Pr ot o c ol A m d 0 3  
 
1 9  
 
2.  
IN T R O D U C TI O N  
2. 1.  
St u d y R ati o n al e  
M D CI  pr o p oses t o e v al u ate bi o mar kers o n t u m or s peci me ns o btai ne d fr o m c o nse nti n g 
ca ncer patie nts a n d t here b y facilitate e nr ol me nt i nt o cli nical trials wit h a ge nts t hat are 
tar gete d t o t he partici pa nt’s t u m or de vel o pe d wit hi n t he G S K t hera pe utic pl atf or ms.  T he 
t u m or s peci me ns a n d dat a c ollecte d d uri n g t h e c o urse of t his st u d y will be st ore d i n a 
G S K Cli nical Scie nce Data base a n d utilize d i n
nal ysis t o pr o vi de i nsi g hts 
i nt o mec ha nis ms c o ntri b uti n g t o s pecific o ut c o mes or resista nce, a n d disc o ver y of n o vel 
tar gets. 
O nc ol o g y, as a fi el d, is m o vi n g a w a y fr o m ‘ u ni v ersal treat me nt’ a n d is e v ol vi n g t o a 
‘ precisi o n me dici ne’ para di g m wit h t hera p y tail or e d t o eac h patie nt’s diseas e. As t he 
n u m ber of si n gle -a n al yt e tests has i ncreas e d wit h t he pers o nalize d me dici ne para di g m, 
o nc ol o gists are face d wit h deci di n g t o use s e veral si n gle -a nal yte tests, or a si n gle Ne xt 
Ge nerati o n Se q ue nci n g ( N G S) test. Beca use i m m u n o hist oc he mistr y (I H C) is a well -
esta blis he d met h o d, e vi d e nce is ne e de d t o bri d ge or c o u ple I H C wit h N G S t o strea mli ne 
testi n g a n d ma k e t his decisi o n easier f or o n c ol o gists. Rece nt data fr o m N CI-M A T C H 
s u p p orts t he use of N G S c o u ple d t o I H C f or m olec ular pr ofili n g; de m o nstr ati n g 
‘feasi bilit y of scree ni n g l ar ge n u m bers of patie nts at n u mer o us accr ui n g sites in a 
c o m ple x trial t o test i n vesti gati o nal t hera pies f or m o deratel y fre q ue nt m ol ec ular tar gets. 
C o -occ urri n g resista nce m utati o ns were c o m m o n a n d e n d orse i n v esti gati o n of 
c o m bi nati o n tar gete d -t hera p y re gi me ns’ [Fla hert y , 2 0 2 0]. T he L u n g -M A P st u d y, w hic h 
has a si milar a p pr oac h, als o s u p p orts t his st u d y desi g n; ‘ As we be gi n t o tar get less 
c o m m o n ge n o mic a n d i m m u n ot hera p y s u bt y p es, ce ntrall y c o or di nat e d cli nical trial 
desi g ns s uc h as L u n g -M A P are necessar y t o ra pi dl y deli ver effecti ve t hera pies t o 
patie nts, w hereas als o ma xi mizi n g t he q ualit y of researc h d ata o btai ne d’ [ La m , 2 0 1 8]. 
T he ce ntr al g oal of t he M D CI pr ot oc ol is t o f urt her dri ve a s hift i n t he directi o n of usi n g 
br oa d m olec ular dia g n osis t o get t he ‘ri g ht p atie nt t o t he ri g ht trial at t he ri g ht ti me’.  
T his m olec ular c haract eri zati o n st u d y will pr os pecti v el y c ollect a n d e x a mi ne eac h 
partici pa nt’s t u m or pr ofil e, al o n g wit h cli nical hist or y, t o use t h ese data i n pr o vi di n g 
a p pr o priate tri al o pti o n(s), w he n a p plica ble. F urt h er, data will be retr os pecti vel y a n al ys e d 
t o a d va nce o ur u n dersta n di n g of bi ol o gical me c ha nis ms u n der pi n ni n g cli nical o utc o mes 
a n d disc o veri n g n o vel p at h wa ys c o ntri b uti n g t o treat me nt resista nce or o nc o ge n esis.  
T he scie ntific rati o nale f or t his st u d y is t hree -f ol d: 
•  T o c ollect se veral bi ol o gi cal sa m ples al o n g wit h i ma gi n g, at c urre nt diseas e  
stat us, f or c orrelati ve a n d dia g n ostic a n al yses; as a n e x a m ple, deter mi ni n g h o w 
cl osel y circ ulati n g t u m or cells ( C T Cs) mi mic disease stat us, wit h t he p ote ntial t o 
m o ve a wa y fr o m bi o ps y pr oce d ure.  
•  T o c ollect data d escri bi n g treat me nt patter ns a n d c orres p o n di n g tr eat me nt 
o utc o mes s uc h as s ur vi val as d oc u me nte d b y t he treati n g p h ysici a n; lear ni n g if 
me dical hist or y i m pacts m olec ular pr ofile a n d mec ha nis ms of resista nce, a n d 
b uil di n g al g orit h ms t o pre dict.  
C CI

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• To increase efficiency at GSK oncology trial sites, moving away from screening a 
patient for one single trial at a time; generating further evidence for use of broad 
molecular profiling. 
Addressing Unmet Needs of Cancer Patients 
Current common practice: patients undergo individual and sequential screening to be 
enrolled in a clinical trial. This can be very time-consuming, especially when the patient 
has to go through the screening process for multiple clinical trials with a low chance of 
being finally included in a precision medicine clinical trial (see schema below): 
 
 
MDCI’s envisaged solution is an operational model that would allow a secure and 
compliant sharing of patient data for those patients who have failed screening for a 
clinical trial, to be considered for an alternative clinical trial without having to undergo 
sequential rounds of biomarker characterization or requiring additional biopsy sampling.  
It is expected that over 600,000 people will die from cancer in 2020; with lung & 
bronchus cancer accounting for most fatalities [American Cancer Society (ACS), 2020]. 
Through compiling a comprehensive dataset (clinical history, imaging, biomarker) for 
each of our patients, we hope to learn of correlative factors that may lend to novel 
therapies, combination strategies, and/or detection methods to address this unmet need 
for patients. Through a simple design, this molecular analysis protocol is expected to 
support participant enrollment into a range of oncology clinical trials within GSK, while 
advancing our understanding of this disease. This study will involve many sites, located 
over a wide geographic footprint, with the intent of significantly expanding the 
opportunities for participant identification and easing the current screening process. 
 

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2.2. 
Background 
GSK oncology is focussed on developing cancer therapies within 4 scientific platforms: 
immuno-oncology, cell and gene therapy, epigenetics, and synthetic lethality.  Each 
of these platforms provides the opportunity for a precision medicine approach through 
agents (e.g. small molecules, antibodies, engineered immune cells) targeting tumor 
expressed biomarkers, as well as potential for combination therapy. As we shift towards 
needing to know multiple biomarkers, molecular signatures and pathways to determine 
potential personalized treatments for our patients, comprehensive screening has become 
critical. 
Immuno-oncology 
Cell & Gene 
Therapy 
Epigenetics 
Synthetic Lethality 
Stimulating anti-
tumor immunity 
Checkpoint 
Blockade 
Cells as medicines 
Target tumor-
specific antigens 
Molecular targeted 
therapies 
Molecular targeted 
therapies 
Combination Therapy 
 
 

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2.2.1. 
Cancer immunotherapies  
Cancer immunity is described as a cyclic multistep process that functions to elicit an 
effective antitumor response [Chen, 2013]. Each of the steps can be negatively regulated, 
thus providing the tumor with redundant mechanisms by which to block an antitumor 
immune response. In some cases, tumors will be highly dependent on a single 
mechanism, and in these cases, there is the potential to achieve significant clinical 
activity with single agent immunomodulatory therapy. However, it is expected that as 
tumors often utilize redundant mechanisms to block an antitumor immune response, 
combination therapy will likely be required. 
Robust antitumor responses including complete cures in some cancers have been 
achieved by modulating patients’ immune system. Antibodies targeting the checkpoint 
receptors and their cognate ligands engaged in negative regulation of T cell responses, 
such as cytotoxic t-lymphocyte-associated protein 4 (CTLA-4) and programmed death 
protein 1 (PD-1/PD) Ligand-1 (PD-L1), have demonstrated clinical efficacy and are 
proven effective as anticancer immunotherapies in a broad range of tumors including 
some solid tumors otherwise considered poorly immunogenic. 
Dostarlimab (TSR-042) is a humanized mAb of the IgG4-κ isotype that binds with high 
affinity to PD-1, resulting in inhibition of binding to PD-L1 and programmed cell death-
ligand 2 (PD-L2). This antibody was generated based on a proprietary platform that utilizes 
affinity maturation to select highly specific antibodies with desired functional 
characteristics. The functional antagonist activity of dostarlimab (TSR-042) was confirmed 
in a mixed lymphocyte reaction assay, demonstrating enhanced interleukin-2 (IL-2) 
production upon addition of dostarlimab (TSR-042).30 Furthermore, dostarlimab (TSR-
042) has an acceptable safety profile based on toxicology studies in cynomolgus monkeys. 
The nonclinical development with dostarlimab (TSR-042) is discussed in the dostarlimab 
(TSR-042) Investigator’s Brochure on file. Dostarlimab (TSR-042) has shown an 
acceptable clinical and nonclinical safety profile. No signals have been identified in clinical 
studies in patients with advanced solid tumors.  
Dostarlimab (TSR-042) binds with high affinity to human and monkey PD-1. Dostarlimab 
(TSR-042) blocks the binding of soluble ligands to human PD-1 that is artificially 
expressed with a half-maximal inhibitory concentration of approximately 1 nM. 
Dostarlimab (TSR-042) enhances T cell activation as measured by the production of IL-2 
from activated human cluster of differentiation 4+ T cells, with a half-maximal effective 
concentration of approximately 1 nM. Full PD-1 receptor occupancy by dostarlimab (TSR-
042) in vitro is achieved at concentrations of approximately 1 μg/mL. Linear 
pharmacokinetics (PK) was observed for dostarlimab (TSR-042) over the range of 10 to 
100 mg/kg in 18 cynomolgus monkeys. Sex had no effect on exposure. The volume of 
distribution at steady state was low and suggested minimal tissue penetration, which is 
consistent with other therapeutic monoclonal antibodies. Weekly administration resulted 
in approximately a 2- to 3-fold increase in dostarlimab (TSR-042) exposure. 
Although antibodies directed against immune checkpoints such as PD-1 and its 
ligand, PD-L1, have proven effective across multiple indications, there is still a large 
unmet medical need for patients who do not respond or who develop resistance during 

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the course of treatment. There are several emerging hypotheses to explain the lack of 
response, including the overall presence and localization of immune cells in the tumor, the 
activity of immunosuppressive cells like regulatory T cells and myeloid-derived suppressor 
cells, as well as the up-regulation of additional T cell checkpoints on the tumor-infiltrating 
lymphocytes. TIM-3 is a novel immune checkpoint initially identified on IFN-γ-producing 
CD4+ T-helper 1 and CD8 T cells and has been implicated in the exhaustion of T cells. 
Up-regulation of TIM-3 expression on PD-1-positive tumor-infiltrating T cells in several 
cancers, such as NSCLC, is associated with reduced proliferation and secretion of 
cytokines important for T cell-mediated antitumor activity. Blocking TIM-3 therefore has 
the potential to restore tumor recognition by T cells and increase tumor killing. Studies 
have demonstrated that blockade of TIM-3 enhances T cell function, as evidenced by 
increased T cell proliferation and release of IFN-γ and IL-2, and this evidence supports 
targeting TIM-3 for tumor immunotherapy. Additionally, research has shown that TIM-3 
blockade combined with paclitaxel promotes activation of dendritic cells, leading to 
increased CD8 T cell activation and antitumor activity [de Mingo Pulido, 2018]. 
Cobolimab is a novel, first-in-class anti-TIM-3 mAb that is in clinical development to treat 
solid tumors in combination with an anti-PD-1 antibody, dostarlimab. Although the 
mechanism of action of TIM-3 is not clearly understood, the current hypothesis is that 
cobolimab will work most effectively in conjunction with anti-PD-1 in tumors that either 
are refractory to anti-PD-(L)1 or have developed resistance after an initial response to 
anti-PD-(L)1.  
The lack of benefit of current treatment options to patients with NSCLC may be due to 
additional immunosuppressive mechanisms, such as those mediated by TIM-3. Early 
combination treatment enables the assessment of TIM-3 and PD-1 blockade to address de 
novo resistance to anti-PD-1 blockade while preventing one of the mechanisms that may 
result in resistance to anti-PD-1 monotherapy.  
Multiple immune checkpoints in addition to PD-(L)1 may regulate T cell anergy and 
modulate antitumor immunity [Topalian, 2011; Mellman, 2011].  Proteins of the nectin and 
nectin-like (Necl1) family, including TIGIT and CD96, have emerged as immune 
suppressing candidates that may prevent immune reactivation after PD (L)1 blockade. 
These co-regulatory receptors modulate the CD226 immune checkpoint, which is one of 
the major activating receptors for NK cells.  
TIGIT is a T-cell immunoglobulin and immunoreceptor tyrosine-based inhibition motif 
domain. TIGIT’s interaction with the ligand CD155 downregulates cytotoxic T and NK 
cells and is a critical regulator of antitumor T cell immunity [Harjunpää, 2020]. TIGIT may 
regulate antitumor immunity through a variety of mechanisms: by inhibiting NK cells from 
releasing tumor antigens, impairing T cell priming by dendritic cells, or inhibiting CD8+ 
effector tumor cell killing [Harjunpää, 2020; Johnston, 2014; Joller, 2014]. The interaction 
of TIGIT with its complementary costimulatory receptor, CD226, is analogous to the 
interaction of CTLA-4 and CD28. TIGIT competes with CD226 for its main ligand, CD155 
[Stengel, 2012; Johnston, 2014], modulating antitumor immunity through multiple 
mechanisms. Binding of TIGIT on T cells with CD155 ligand on dendritic cells impairs 
CD4+ T cell function [Chauvin, 2020]. In addition, binding of TIGIT prevents 
homodimerization and activation of CD226 on CD8+ T cells [Johnston, 2014]. TIGIT also 

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interacts weakly with other co-regulatory inhibitors of the CD226 pathway including 
CD112, CD113, and CD114. TIGIT is upregulated on tumor infiltrating CD8+ T cells and 
a population of infiltrating CD4+ T cells in solid tumors in comparison to peripheral T cells 
from patients and normal donors. CD8+ and CD4+ TIGIT-expressing T cells also co-
express PD-1. 
CD96 represents a novel immune-checkpoint receptor target. Engagement of CD96 by a 
related ligand on antigen-presenting cells and cancer cells, CD155, functions as an 
‘off switch,’ or immune checkpoint, to downregulate immune responses. GSK6097608 is 
a mAb checkpoint inhibitor designed to modulate this axis by forming a high-affinity 
complex with CD96, disrupting CD96:CD155 binding and redirecting CD155-mediated 
costimulatory signaling through the activating receptor CD226 to increase T-cell and 
NK-cell antitumor activity. Modulation of this axis via inhibition or deletion of CD96 has 
resulted in antitumor activity in mouse tumor models alone and in combination with 
PD-1 inhibition [Blake, 2016; Harjunpää, 2018]. 
An antibody currently in development by GSK, GSK4381562, is fully-human IgG1 
antagonist antibody that binds to Poliovirus Receptor-related Immunoglobulin Domain 
Containing (PVRIG), preventing inhibitory CD112 (ligand) interactions, thereby 
promoting improved T and NK cell function. Blockade of PVRIG/CD112 interactions 
can also redirect CD112 to the co-stimulatory receptor CD226/DNAM-1, further 
promoting enhanced T/NK cell function. PVRIG binds to a distinct epitope on PVRIG 
and is also a fully Fc-competent backbone (IgG1), providing a potential functional 
advantage relative to the human IgG4 PVRIG antagonist COM701. Based on evidence 
supporting the molecular interplay between pathways and the utility of addressing diverse 
immune populations, GSK4381562 may not only work in concert with PD-(L)1 
(programmed cell death protein 1 and/or programmed death ligand 1) inhibition, but also 
benefit patients who are refractory to, or have developed resistance to, current T cell-
based therapeutics. 
 
2.2.2. 
Cell and Gene Therapy (TCR engineered adoptive T-cell therapy 
targeting NY-ESO-1/LAGE-1a) 
In contrast to indirect activation of host immune cells within the tumor microenvironment 
using checkpoint inhibitors,  adoptive T‑cell therapy (ACT) is a personalized therapeutic 
approach involving direct infusion of cytotoxic T cells derived from the cancer patient 
(autologous) or another donor (allogeneic) that target a protein expressed on their cancer 
cells and can infiltrate the tumor, target and destroying tumor cells.  T cells for ACT have 
been used in various forms: native unmodified (tumor infiltrating cells) or engineered T-
cells targeting tumor antigens.  Engineered T cells currently under evaluation either 
express a chimeric antigen receptors (CARs) or affinity-enhanced T cell receptors 
(TCRs).  T cells are obtained from the participant by leukapheresis and can then be 
engineered to express CARs or affinity enhanced TCRs, that can target respectively, 
cancer cell surface expressed proteins, or epitopes of internal tumor-associated antigens 
(TAAs) presented in complex with HLA molecules to the cancer cell surface. 

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CAR engineered T-cell therapy directed at CD19 is approved for use in paediatric Acute 
Lymphoblastic Leukemia (ALL) and Diffuse Large B-cell Lymphoma (DLBCL). 
For TCRs, the patient’s T cells are engineered with a human lentivirus that expresses a 
tumor-specific TCR.  These TCR‑Ts are expanded in vitro and then re-infused into the 
participant.  TCRs provide the opportunity to target intracellular antigens that are 
processed and presented by the major histocompatibility complex (MHC) known as 
Human Leukocyte Antigen (HLA) protein in humans [Schmitt, 2015]. Screening for both 
HLA and antigen is needed for TCR therapy. The TCR-modified T cell approach is also 
particularly suited for solid tumors due to their ability to recognize low concentrations of 
these intracellular cognate antigens.  In addition, the TCR approach mimics the natural 
function of the T cell by recruiting the endogenous signalling molecules and adhering to 
correct spatial orientation between the T cell and its target.  These aspects may contribute 
to a manageable safety profile, high anti-tumor activity and enhanced persistence of the 
infused TCR engineered T cells, providing ongoing anti-cancer protection.  
2.2.2.1. 
Background for Current GSK TCR-T cells 
GSK is developing a number of different TCR‑T cells, including GSK3377794 (NY-
ESO-1 TCR engineered T-cells), GSK3901961 (NY-ESO-1 TCR engineered T-cells co-
expressing the α-chain of the CD8 co-receptor) & GSK3845097 (NY-ESO-1 TCR 
engineered T-cells coexpressing the dnTGF-βRII receptor). These TCR‑T cells target the 
cancer testis antigens (CTAs) NY-ESO-1 and LAGE-1a, tumor-associated proteins found 
in several tumor types including synovial sarcoma and non-small cell lung cancer 
(NSCLC).   
Treatment with GSK3377794 has demonstrated encouraging clinical responses in 
patients with SS, inducing a clinical response in 50% of treated SS patients with a 
manageable safety profile. This therapy is currently being explored in other tumors 
including NSCLC, Myxoid round cell liposarcoma (MRCLS), and multiple myeloma.   
One requirement of all TCR-directed therapies is that the engineered TCR must recognize 
a peptide epitope of the TAA that is processed and presented on the tumor cell surface, in 
complex with the participant’s own HLA protein.  GSK TCR‑T GSK3377794 is 
engineered to recognize antigens complexed with HLA-A*02:01, HLA-A*02:05, and 
HLA-A*02:06, which means that only those participants with at least one of these HLA 
alleles potentially may respond to this TCR‑T.   
The lentiviral vectors used for manufacturing of GSK3377794 trigger expression of the 
same affinity-enhanced TCR designated as clone NY-ESO-1c259 that is optimized to 
recognize the SLLMWITQC peptide, which is derived from the cancer testis antigens 
(CTAs) family members NYESO-1 and LAGE-1A. The final T‑cell product is comprised 
of autologous cluster of differentiation 4 (CD4) and cluster of differentiation 8 (CD8) T 
cells that have been transduced with this lentiviral vector. The product of this 
transduction is polyclonal T cells which are designed to target NY-ESO-1 and/or LAGE-
la positive cells; consequently, only those participants with tumors positive for NY-ESO‑
1 and/or LAGE-1a and the right HLA-A*02 allelic variant will potentially respond to 

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current GSK TCR‑T cells.  Future versions of the GSK TCR‑T cells may target 
additional tumor antigens. 
2.2.2.2. 
Background for HLA & Screening 
Specific peptide epitopes of the NY-ESO-1 or LAGE-1a protein are processed and 
presented on the surface of the tumor cell in complex with an HLA molecule, which can 
be recognized by T cells. The enhanced affinity TCR-T cells recognize the target antigen 
peptide fragment when it is bound to any HLA-A*02 allelic variants HLA-A*02:01, 
HLA-A*02:05, and HLA-A*02:06. These variants are three of the most common 
subtypes and are carried by roughly 45% [Gonzalez-Galarza, 2015] of the world’s 
population overall. Background for NY-ESO-1 TCR Target Antigens & Screening 
NY-ESO-1 and LAGE-1a are members of the cancer-testis antigen (CTA) family of 
tumor-associated antigens and are expressed at different frequencies in different tumor 
types. These are cytoplasmic proteins detectable in multiple cancer types including non-
small cell lung cancer (NSCLC), bladder cancer, melanoma, liver cancer, synovial 
sarcoma (SS), myxoid/round cell liposarcoma (MRCLS), multiple myeloma and many 
others. For example, about 76% of the patients with synovial sarcoma test positive for 
NY ESO 1 antigen [Lai, 2012; Endo, 2015].  In contrast, only roughly 10% of patients 
with NSCLC test positive for the NY ESO 1 and/or LAGE 1a antigens. NY-ESO-1 and 
LAGE-1a are expressed in tumor types other than those in current clinical trials. By 
analyzing all tumor types for these markers, we have the capability to better design our 
trials and have insight into potential combination therapies. 
2.2.3. 
Synthetic Lethality Therapy 
Niraparib is an orally available, potent, and highly selective poly (adenosine 
diphosphate-ribose) polymerase (PARP)-1 and PARP-2 inhibitor. Zejula™ (niraparib) 
was approved for the maintenance treatment of women with recurrent epithelial ovarian, 
fallopian tube, or primary peritoneal cancer who are in a complete response (CR) or 
partial response (PR) to platinum-based combination chemotherapy by the United States 
(US) Food and Drug Administration (FDA) on 27 March 2017 and received a Marketing 
Authorization in the European Union (EU) on 16 November 2017. In an analysis of 
approximately 500 high-grade serous ovarian cancer tumors, approximately 50% 
contained homologous recombination defects, which could sensitize tumors to poly 
(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) [TCGA, 2011]. 
 
Development of more efficacious treatment options for patients with NSCLC remains a 
high unmet need. Novel combination therapy regimens are needed with acceptable safety 
profile that deliver clinically meaning improvement in progression-free and overall 
survival when administered in the maintenance setting for patients with 
advanced/metastatic NSCLC whose disease did not progress with frontline 
pembrolizumab/platinum-based therapy. In the Phase 2 JASPER study (Study 3000-02-
001), data provided support of the safety of the combination of niraparib and 
pembrolizumab in NSCLC. The combination of niraparib with pembrolizumab in this 
first-line treatment setting showed antitumor activity, with the highest response rate 
observed in participants with high PD-L1 expression. 

T M F -1 3 8 5 5 5 4 1  
C O N FI D E N TI A L  
 
 
 
2 1 3 2 9 9  
 
Pr ot o c ol A m d 0 3  
 
2 7  
 
 
I n t he T O P A CI O/ K E Y N O T E-1 6 2 st u d y, t h e c o m bi nati o n of nira pari b pl us 
pe m br oliz u ma b pr o vi de d pr o mis i n g a ntit u m or acti vit y i n b ot h a d va nce d or metastatic 
tri ple-ne gati ve breast c a n cer, wit h n u meri call y hi g her res p o ns e rates i n t h os e wit h t u m or 
breast c a ncer s usce pti bilit y ge n e ( B R C A) a n d rec urre nt o vari a n ca n cer 
[K o nsta nti n o p o ul os , 2 0 1 9; Vi na ya k , 2 0 1 9]. T he c o m bi nati o n t hera p y was safe wit h a 
t olera ble safet y pr ofile.  
 
Please refer t o relate d I B f or u p -t o-dat e i nf or mati o n o n G S K t hera pies.  
2. 3.  
B e n efit/ Ri s k A s s e s s m e nt  
A ke y be nefit of M D CI is t he use of o ne sa m pli n g strate g y t o deter mi ne c urre nt disease 
c haracteristics, a n d t o scree n partici p a nts f or m ulti ple cli nical trials base d o n t he res ults, 
eli mi nati n g t he ti me a n d li mitati o ns i n v ol ve d i n se q ue ntial scree ni n g.  T h e br oa der 
dataset ge nerate d t hr o u g h t he
a nal yses wit hi n t his st u d y will f urt her i nf or m 
t he mec ha nis ms of resista nce a n d res p o nse a n d m a y als o i nf or m m ore a p pr o priate ne xt 
t hera pies f or t he patie nt, a n d disc o ver y of a d diti o nal t hera pe utic, pr o g n ostic or dia g n ostic 
bi o mar kers.  
T he res ults of cli nical a n d n o n -cli nical st u dies of G S K t hera pe utics ca n be f o u n d i n t he 
relate d I B.  
2. 3. 1.  
Ri s k A s s e s s m e nt  
N o i n vesti gati o nal t hera p e utic pr o d uct is use d i n t his st u d y; c o nse q ue ntl y, t here are n o 
ris ks d ue t o e x p os ure t o st u d y dr u g. M D CI is pri m aril y a n
st u d y t hat ma y 
i nf or m s u bse q ue nt cli nical trial eli gi bilit y.  Ris k r es ulti n g fr o m use of t he i n vesti gati o nal 
de vice res ults var y f or eac h res pecti ve s u bse q ue nt t hera pe utic 
 
pri mar y ris k t o patie nts 
prese nte d b y t his pr ot oc ol is t he ris k ass ociate d wit h s peci me n ac q uisiti o n.   
T u m or bi o ps y is a c o m m o n pr oce d ure i n ca n cer t h era p y as it is t he c or nerst o ne of 
dia g n ostic a n d t h era p e utic decisi o ns i n o nc ol o g y.  T he ris ks of t he bi o ps y ma y i n cl u de 
pai n, bl o o d l oss, i nfecti o n, a n d ot her a d v erse e ve nts ass ociate d wit h s ur ger y i n ge n eral 
a n d ass ociate d wit h s ur ger y at t he gi ve n a nat o mical l ocati o n.  T he sites are directe d t o 
ta ke all a p pr o priate safet y me as ures t o pr otect t he well-bei n g of t he p artici pa nt a n d t o 
f oll o w-u p o n a n y a d v erse e ve nt ( A E) t h at w o ul d be relate d t o t he st u d y pr oce d ure.   
Rece nt data p u blis he d fr o m pa n -t u m or st u d y N CI-M A T C H relat e d t o A Es d ue t o bi o ps y 
pr oce d ure deter mi ne d ‘ of 4, 6 2 7 patie nts wit h data, 2 6 ( 0. 6 %) a n d 7 ( 0. 2 %) e x perie nce d 
gra de 3 a n d 4 e ve nts, r es pecti vel y. N o deat hs were relate d t o t he bi o ps y pr oce d ure’ 
[Fla hert y , 2 0 2 0]. 
If a patie nt h as ha d a bi o ps y pri or t o M D CI Visit 2 as part of sta n d ar d of care, t hat bi o ps y 
ma y b e acce pte d as t he M D CI t u m or s peci me n ( See Secti o n 7. 7. 1 ). If a n arc hi val t u m or 
s peci me n is n ot a vaila ble f or scree ni n g, s ur pl us tiss ue fr o m sta n dar d of care pr oce d ures 
are acce pta ble bef ore fres h bi o ps y ma y be o btai n e d. F or t h ose patie nts u n d er g oi n g a ne w 
bi o ps y, t he l ocati o n of t h e bi o ps y ma y b e fr o m eit her t he pri mar y t u m or l o cati o n or a n y 
ot her metastatic t u m or site. T h us, p h ysi cia ns ma y c h o ose a n a n at o mic site  f or t he bi o ps y 
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that presents an acceptable risk to the patient based on the overall status of the patient as 
well as the accessibility of the tumor.  Radiologic guidance will be used for biopsy 
collection whenever possible.  Biopsies will be collected using low-risk procedures that 
have an anticipated serious complication rate <2%.  The informed consent form will 
clearly indicate that a biopsy may be needed and that participation on the study is 
optional so the patient is well-informed and may choose not to participate if he/she does 
not consent 
Each patient is asked to provide 4 samples of whole blood at the second visit. There is a 
risk that the patient could experience complications due to these blood draws (e.g., pain, 
bleeding and/or bruising and possibly infection), although serious complications are 
likely to be very rare. 
All procedures of blood collection and tumor biopsy must follow institutional standards. 
Radiographic imaging for this study will cause no additional risk compared to standard of 
care radiological procedures typically conducted for participants with tumors. Imaging 
with computed tomography (CT) requires exposure to radiation. The effective radiation 
dose of a CT scan required for this study is approximately 20 mSv, which corresponds to 
about 10 times the average natural radiation a person is exposed to annually. The use of 
IV iodinated contrast is preferred for CT procedures in this study. Participants may be at 
risk of contrast sensitivity or an allergic reaction to the CT contrast agent. Magnetic 
resonance imaging (MRI) does not involve exposure to radiation, however due to the 
magnetic field there are risks for participants who may have metal implants, pacemakers, 
or other permanent magnetic devices which may shift or become dislodged and cause 
damage to surrounding tissue. Gadolinium-based contrast agents used in MRI are 
associated with the risk of nephrogenic systemic fibrosis in some participants who have 
reduced renal function. Any participant who will undergo an MRI should be screened by 
the institution for metal and contrast administration safety prior to scanning. All imaging 
procedures must be conducted following institutional standards and safety precautions.  

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Risk Assessment 
Risks of Clinical Significance 
(Potential) 
Summary of Data/Rationale 
for Risk 
Mitigation Strategy 
Tumor biopsy/Blood Samples 
Bleeding, pain, swelling, 
infection, associated with the 
procedure &/or site of biopsy 
Blood samples collected & 
biopsies are performed by 
trained personnel.  Image-guided 
when necessary and performed 
only if deemed safe. Sites will 
utilize standard pre-biopsy 
screening measures (such as 
blood tests for platelets, and 
coagulation).  The informed 
consent will identify any 
potential risks based on the site 
of the biopsy. 
CT and MRI risks 
Risk of contrast sensitivity or 
allergic reaction to the CT 
contrast agent.  MRI - risks for 
participants who may have metal 
implants pacemakers, or other 
permanent magnetic devices 
which may shift or dislodged 
and cause damage to 
surrounding tissue.   
All imaging procedures will 
follow institutional standards 
and safety precautions. 
Assay Results 
Risk of false positives and/or 
false negatives from assays used. 
All assays used to determine 
protocol trial eligibility have 
demonstrated acceptable 
Negative Predictive Value 
(NPV) and Positive Predictive 
Value (PPV). 
 
2.3.2. 
Benefit Assessment 
The most direct potential benefit to participants in this study is to determine if they may 
be eligible to enter an intended treatment protocol based on clinical history and 
biomarker testing and analysis of their disease. Other benefits may include but not be 
limited to contributing to the understanding of disease, and having the opportunity to 
contribute to scientific knowledge overall via: providing data to support understanding of 
disease outcomes, the blood sample designated for genetics research, to the development 
of a liquid rather than solid tumor‑based companion diagnostic via the liquid biopsy 
sample. 
2.3.3. 
Overall Benefit: Risk Conclusion 
The primary benefit to patients is providing the opportunity to be assessed for multiple 
treatment options (as opposed to one); potentially decreasing time-to-treatment, & 
multiple procedures. The MDCI protocol also gives patients access to trials for which 
they may otherwise not have been screened. Key risk in this pre-screening protocol are 
those associated with tumor biopsies. After balancing the risks associated with collection 
of a tumor biopsy (a standard procedure in the treatment of a cancer patient) with the 
benefits, it would appear the benefits outweigh the risks.    

T M F -1 3 8 5 5 5 4 1  
C O N FI D E N TI A L  
 
 
 
2 1 3 2 9 9  
 
Pr ot o c ol A m d 0 3  
 
3 0  
 
3.  
O B J E C TI V E S A N D E N D P O I N T S 
 
O bjecti ves  
E n d p oi nts  
Pri mar y  
Pri mar y  
•  
T o 
e val uate 
m olec ular 
a n d 
i m m u n ol o gical 
pr ofile 
of t u m or 
a n d 
peri p heral 
bl o o d 
of 
all 
e nr olle d 
partici pa nts, acr oss i n dicati o ns a n d wit hi n 
t u m or s u bsets ( B uil di n g a G S K Cli nical 
Scie nce D ata bas e f or t u m or pr ofili n g a n d 
c orrel ati ve st u dies)  
•  Pr ofile of patie nt s pecific selecti o n 
bi o mar kers tar get e d b y t hera pe utics 
wit h t he G S K o nc ol o g y pi peli ne, as 
well as ot her
 as 
detaile d i n t he st u d y refere nce ma n ual 
( S R M). 
C CI
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T M F -1 3 8 5 5 5 4 1  
C O N FI D E N TI A L  
 
 
 
2 1 3 2 9 9  
 
Pr ot o c ol A m d 0 3  
 
3 1  
 
Ta ki n g i nt o acc o u nt t he meas ures ta k e n t o mi ni mize ris k t o partici pa nts partici pati n g i n 
t his st u d y, t he p ot e ntial ris ks i de ntifie d i n ass ociati o n wit h t his st u d y are j ustifie d b y t he 
a ntici pate d be nefits t hat ma y b e aff or de d t o partici pa nts.  
 
4.  
S T U D Y D E SI G N  
4. 1.  
O v er all D e si g n  
T his is a m ultice nter st u d y, e nr olli n g patie nts wit h a d va nce d/ metastatic dise ase f or t he 
p ur p ose of c ollecti n g t u m or tiss ue a n d bl o o d sa m ples f or br oa d m olec ular a nal ys is a n d 
e x a mi ni n g t he e x pressi o n of s pecific bi o mar kers usi n g vali date d cli nical assa ys. T h e 
st u d y i n v ol ves t hree pri mar y visits (Fi g ure 1 ). 
C CI

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Figure 1 
Study Schema 
 
Footnotes: 1MDCI will be an optional protocol under select GSK oncology protocols; 2In the case that Visit 
1 and 2 are combined, all corresponding samples must be collected per the SoA (Section 1.3 Table 1) at this 
visit and after eligibility is confirmed; 3Subset of data to be shared on Gather Share Know; 4Patient’s 
molecular profile and medical history will be compared against the eligibility criteria of select GSK 
oncology protocols to identify potential trial options; 5Visit 3 may occur remotely via telehealth/phone visit 
(optional). 
At Visit 1, informed consent will be obtained from participants to enroll in the study, 
specifically to undergo a multiplex biomarker characterization, and to store  and share a 
subset of their data through a Participant Hub (Gather Share Know). Registering for 
Gather Share Know is optional; a standardized template will be created and included as 
an annexure to the regular ICF.  
Upon consenting to participate in the MDCI screening process, the participant will 
continue with assessments per schedule of activities (SoA Table 1).   For most 
participants, the expected duration between V1 and V3 is 8 weeks; which is dependent 
on the receipt and the type of tumor biopsy sample submitted. 
During Visit 2, a tumor specimen will be collected or submitted, as per tumor specimen 
collection requirements (refer to SRM and Study Laboratory Manual).  The specimen 
will be evaluated by IHC to determine the expression of tumor specific antigens and 
immune markers such as, but not limited to, NY-ESO-1 and PD-L1.  A portion of the 
tumor specimen will also be analysed by whole exome sequencing (WES), as well as 
whole transcriptome sequencing (WTS) to determine patients’ molecular profile; these 
sequencing data will not be used for trial referral.  
A liquid biopsy (blood) will also be taken at Visit 2 to analyse 
 
circulating tumor DNA (ctDNA),
 and/or exosomes. In addition, 
participants will also provide mandatory blood samples for biomarker, validated clinical 
biomarker testing, and genetic research, as well as tumor imaging with CT/MRI. HLA 
genotype will be determined from whole blood DNA tested at a central laboratory. 
CCI
CCI

T M F -1 3 8 5 5 5 4 1  
C O N FI D E N TI A L  
 
 
 
2 1 3 2 9 9  
 
Pr ot o c ol A m d 0 3  
 
3 3  
 
 W E S data fr o m t he bl o o d will als o be use d i n c o nj u ncti o n wit h t he S N P 
ge n ot y pi n g dat a t o assess t he effect of h ost ge n etic variati o n i n o ne or m ore ca n di date 
ge n es or acr oss t he ge n o me o n ca ncer ris k, p r o gressi o n, a n d res p o nse t o ca ncer 
treat me nts.  Details of testi n g a n d ma na ge me nt of all sa m ples ca n be f o u n d i n t he 
res pecti ve s ecti o ns of t he S R M a n d St u d y La b orat or y M a n ual. 
A s u bset of t he ge n erate d res ults will be u pl oa de d t o t he P h ysicia n P ortal f or re vie w, 
f oll o we d b y t he Gat her S hare K n o w Partici pa nt H u b.  P h ysicia ns will re vie w t he res ults 
wit h partici pa nts at Visit 3 . If t he res ults i n dicate eli gi bilit y f or a s pecific cli nical trial, 
a p pr o priate referrals t o t h ose trials will be ma de b y p h ysicia n f or f urt her scree ni n g.   
Partici pa nts will o nl y be pr o vi de d access t o t heir s electe d res ults t hr o u g h t h e Gat her 
S hare K n o w Partici p a nt H u b after t h e y ha ve recei ve d i nf or mati o n o n t he 
si g nifica n ce/ be n efits of t he testi n g. Trai ni n g will be pr o vi de d t o all partici pa nts w h o 
c o nse nt o n h o w t o access a n d na vi gate t he h u b.   
All partici pa nts will u n der g o a f oll o w -u p safet y assess me nt f or a n y seri o us a d verse 
e ve nts ( S A Es) ass esse d as relate d t o pr ot oc ol -m a n date d st u d y pr oce d ures or lea di n g t o 
st u d y wit h dra w al.  
T he  st u d y pr ot oc ol will re mai n o pe n u ntil all desi g nat e d G S K-s p o ns ore d i m pacte d 
cli nical trials ( o utli ne d i n S R M) are cl ose d t o e nr ol me nt & all partici pa nts h a ve 
c o m plete d t his st u d y or at t he discreti o n of G S K.  
P artici p a nts i neli gi ble f or Cli nic al tri als  
If a patie nt d o es n ot e nr oll o nt o a G S K st u d y, or a n y ot her i n v esti gati o nal st u d y, , a n d 
w h o pr occe d t o recei ve Sta n dar d of Care ( S o C) t h era p y, dise ase will c o nti n ue t o be 
m o nit ore d u n der M D CI f oll o wi n g a se p arat e Sc he d ule of Acti vities ( S o A) f or 
l o n git u di nal f oll o w-u p ( T a ble 2 ). Acc or di n gl y, p h ysicia ns will be as ke d t o e nter/ re p ort 
all a ntica ncer t hera pies recei ve d a n d t he partici pa nt’s s ur vi val stat us d uri n g f oll o w -u p, i n 
or der t o c h aracteriz e treat me nt patter ns a n d s ur vi v al o utc o mes res pecti vel y.  
T he f oll o wi n g p ort als will be use d f or t his st u d y:  
1.  G at her S h are K n o w P artici p a nt H u b  
T he ‘ Gat h er S hare K n o w’ Partici pa nt H u b was d esi g ne d a n d de vel o pe d b y t he 
M D CI te a m i n c olla b orati o n wit h a n e xter nal part ner. T his p o werf ul t o ol h as 
se ver al o bjecti ves w hic h i ncl u de: c o n necti n g with o ur p atie nts, directi n g o ur 
p atie nts t o cre di ble s o urces, m a ki n g o ur p atie nts a w are of ‘ w h at t o e x pect’ at 
st u d y visits, ret ur ni n g i n v al u a ble v ali d ate d cli nic al bi o m ar ker d at a ( will n ot 
i ncl u de ger mli ne se q ue nci n g d at a), pr o vi di n g t he m cli nic al tri al o pti o ns, a n d 
offeri n g c o nti n ue d f oll o w -u p. T his t o ol als o ca n als o pr o vi de ca p a bilit y t o all o w 
partici pa nts t o ta ke part i n s ur ve ys.  Patie nts will be pr o vi de d wit h trai ni n g o n t he 
Gat her S hare K n o w Partici pa nt H u b pri or t o bei n g gi ve n access. T his trai ni n g w ill 
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include an overview of the type of information that will be provided, how to use 
the portal and potential benefits.  
 
2. Physician Portal 
The ‘Physician Portal’ is a web-based compilation of a patient’s clinical history 
and molecular data collected in this study, as well as a list of applicable clinical 
trials based on validated clinical assays that has been established by the 
sequencing vendor. A major benefit of this portal is the ability for physicians to 
compare the molecular profiles of all their patients that have enrolled into the 
MDCI study side-by-side. 
 
GSK Clinical Science Database  
 
To better understand our patients’ disease, novel pathways/targets, mechanisms of 
action or resistance, disease progression and molecular change, clinical trial design, and 
potential combination strategies, all data collected (examples below) will be compiled 
into a GSK Clinical Science Database: 
o Demographics 
o Clinical disease & treatment history 
o Tumor molecular profiling (IHC & sequencing) 
o Liquid biopsy profiling 
o Patient questionnaires 
4.2. 
End of Study Definition 
A participant will be determined to have completed the study for the primary objectives 
if: 
• The participant signed consent to participate on one of the GSK treatment 
protocols 
• After two years of longitudinal follow-up (Table 2) 
The protocol will remain open until all designated GSK-sponsored clinical trials are 
closed to enrolment and the last participant in this study has completed their last visit or 
until a date otherwise determined at the discretion of GSK. 
5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrolment criteria, also 
known as protocol waivers or exemptions, is not permitted. 
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria 
apply: 

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Intended and Alternative Treatment Protocols 
1. Participant is a candidate for molecular screening for a GSK precision therapeutic 
clinical study (the Intended Treatment Protocol) that is being conducted in parallel at 
or nearby the MDCI recruitment site. 
2. Participant is willing to travel to a site recruiting for the intended GSK treatment 
protocol (or alternative treatment protocol), if feasible, and if, in the investigator’s 
opinion, the patient would benefit from enrolment into the intended GSK treatment 
protocol at an alternative clinical site. See 213299 Study Reference Manual (SRM) for 
the most recently updated lists of recruiting treatment trials. 
Type of Participant and Disease Characteristics 
3. Confirmed advanced/metastatic diagnosis of solid malignancy, as described in the 
Intended Treatment Protocol, including but not limited to the following disease-
areas: NSCLC, HNSCC, Breast, Ovarian, CRC 
4. Life expectancy of >6 months. 
5. Able to provide blood samples (see Section 7.7 for blood volume requirements). 
6. Able to provide an archival formalin-fixed paraffin-embedded (FFPE) tumor specimen 
from a current lesion/most current setting . If an archival tumor specimen is not available, 
surplus tissue from standard of care procedures is acceptable before fresh biopsy may be 
obtained. If an archival block cannot be sent as per institutional guidance/policy, slides 
can be sent instead, refer to the respective sections of the SRM and Study Laboratory 
Manual for further details. 
Sex 
Female 
Contraceptive use by women should be consistent with local regulations regarding the 
methods of contraception for those participating in clinical studies. Contraceptive use is a 
requirement for females as pregnancy is an exclusion for this study.  
7. Female Participants:  
• 
A female participant is eligible to participate if she is not pregnant or 
breastfeeding, and at least one of the following conditions applies: 
o Is not a woman of childbearing potential (WOCBP)  
OR 
o Is a WOCBP and using a contraceptive method that is highly effective 
(with a failure rate of <1% per year), preferably with low user 
dependency, as described in Appendix 4.  
o A WOCBP must have a negative highly sensitive pregnancy test (urine or 
serum) as required by local regulations) within 24 hours before tumor 
biopsy.  

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o  If a urine test cannot be confirmed as negative (e.g., an ambiguous result), 
a serum pregnancy test is required. In such cases, the participant must be 
excluded from participation if the serum pregnancy result is positive.  
• 
Additional requirements for pregnancy testing during and after study are located in 
Appendix 2. 
• 
The investigator is responsible for review of medical history, menstrual history, and 
recent sexual activity to decrease the risk for inclusion of a woman with an early 
undetected pregnancy 
Informed Consent 
8. Capable of giving signed informed consent as described in Appendix 1 which includes 
compliance with the requirements and restrictions listed in the informed consent form 
(ICF) and in this protocol.  
9. Male or female, age ≥18 years; at the time consent is obtained (minimum age 
requirement per local regulatory requirements). 
5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
1. ECOG Performance Status >2 
2. History of myocardial infarction, acute inflammatory heart disease, unstable angina, or 
uncontrolled arrhythmia within the past 6 months.  
3. For female participants, pregnancy 
4. Any serious and/or unstable pre-existing medical, psychiatric disorder or other 
conditions that could interfere with the subject’s safety, obtaining informed consent or 
compliance to the screening study procedures. 
5.3. 
Screen Failures 
Screen failures are defined as participants who consent to participate in Study 213299 but 
are not subsequently entered in the study. A minimal set of screen failure information is 
required to ensure transparent reporting of screen failure participants to meet the 
Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes 
demography, screen failure details, eligibility criteria, any protocol deviations and any 
serious adverse events (SAEs). 
Individuals who do not meet the criteria for participation in this study (screen failure) 
may be rescreened.  
All samples (tumor and blood) and radiographic imaging collected from screen failure 
participants may be used for further biomarker, companion diagnostic, disease 
characterization, and/or genetic research. 

T M F -1 3 8 5 5 5 4 1  
C O N FI D E N TI A L  
 
 
 
2 1 3 2 9 9  
 
Pr ot o c ol A m d 0 3  
 
3 7  
 
C o nse nt t o a n ot her i nte n de d treat me nt pr ot o c ol a n d t u m or rea nal ysis are all o we d after 
disc ussi o n wit h S p o ns or.  
6.  
S T U D Y I N T E R V E N TI O N 
St u d y i nter ve nti o n is defi ne d as a n y i n vesti gati o nal i nter venti o n(s), mar ket e d pr o d uct(s), 
place b o , or me di cal de vi ce (s) i nte n d e d t o be a d mi nistere d t o a st u d y p artici pa nt acc or di n g 
t o t he st u d y pr ot oc ol.  
N o i n vesti gati o nal t hera p e utic pr o d uct will be use d i n St u d y 2 1 3 2 9 9. M D CI is pri maril y 
a n
st u d y t hat ma y i nf or m s u bse q ue nt cli nical trial eli gi bilit y. T h era pe utic 
i nter ve nti o ns res ulti n g fr o m use of t he i n vesti gati o nal de vice res ults var y f or eac h 
res pecti ve s u bs e q ue nt t hera pe utic cli nical st u d y pr ot oc ol a n d will t heref ore be descri b e d 
u n der t h ose s peci fic pr ot oc ols. C o nse q ue ntl y, t he f oll o wi n g secti o ns are n ot a p plica ble t o 
t his pr ot oc ol: 
St u d y I nter v e nti o n(s) A d mi nistere d  
Pre parati o n/ Ha n dli n g/ St ora ge/ Acc o u nta bilit y  
Meas ures t o Mi ni mize Bias:  Ra n d o mizati o n a n d Bli n di n g  
St u d y I nter v e nti o n C o m plia nce  
C o n c o mita nt T hera p y 
D ose M o dificati o n  
I nter ve nti o n aft er t he E n d of t he St u d y 
6. 1.  
P arti ci p a nt Di s c o nti n u ati o n/ Wit h dr a w al fr o m t h e St u d y  
•  
A partici pa nt ma y wit h dr a w fr o m t he st u d y at a n y ti me at his/ her o w n re q uest or 
ma y b e wit h dra w n at a n y ti me at t he discreti o n of t he i n vesti gat or f or safet y, 
be ha vi o ural, c o m plia n ce or a d mi nistrati ve reas o ns. T his is e x pecte d t o be 
u nc o m m o n.  
•  
At t he ti me of disc o nti n ui n g fr o m t he st u d y, if p ossi ble, a n earl y disc o nti n u ati o n 
visit s h o ul d be c o n d ucte d, as s h o w n i n t he S o A. See S o A f or data t o b e c ollecte d 
at t he ti me of st u d y disc o nti n uati o n a n d f oll o w -u p a n d f or a n y f urt her 
e val uati o ns t hat nee d t o b e c o m plete d.  
•  
If t he partici p a nt wit h dra ws c o nse nt f or discl os ur e of f ut ure i nf or mati o n t he 
s p o ns or ma y retai n a n d c o nti n ue t o use a n y d ata a n d i ma ges c ollecte d  b ef ore 
wit h dra wal of c o nse nt.  
•  
If a partici pa nt wit h dra ws fr o m t he st u d y, t he y m a y re q uest destr u cti o n of a n y 
sa m ples ta ke n a n d n ot teste d, a n d t he i n vesti gat or m ust d oc u me nt t his i n t he site 
st u d y rec or ds a n d i nf or m t he s p o ns or. 
6. 2.  
L o st t o F oll o w U p  
A partici pa nt will be c o nsi dere d l ost t o f oll o w -u p if t he y re peate dl y fail t o r et ur n f or 
sc he d ule d visits a n d is u na ble t o be c o ntacte d b y t he st u d y site.  
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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 whether or not the participant wishes to 
and/or should continue in the study. 
• 
Before a participant is deemed lost to follow up, the investigator or designee 
must make every effort to regain contact with the participant (where possible, 3 
telephone calls and, if necessary, a certified letter to the participant’s last known 
mailing address or local equivalent methods). These contact attempts should be 
documented in the participant’s medical record. 
• 
Should the participant continue to be unreachable, he/she will be considered to 
have withdrawn from the study.  
Discontinuation of specific sites or of the study as a whole are handled as part of 
Appendix 1. 
7. 
STUDY ASSESSMENTS AND PROCEDURES 
• 
Study procedures and their timing are summarized in the SoA.  
• 
Protocol waivers or exemptions are not allowed.  
• 
Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct. 
• 
All Visit 1 evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening 
log to record details of all participants screened and to confirm eligibility or record 
reasons for screening failure, as applicable.  
• 
Procedures conducted as part of the participant’s routine clinical management (e.g., 
tumor imaging studies, blood count) and obtained before signing of ICF may be 
utilized for screening or baseline purposes provided the procedure met the protocol-
specified criteria and was performed within the time frame defined in the SoA. 
• 
The maximum amount of blood collected from each participant over the 
duration of the study, including any extra assessments that may be required, will 
not exceed 200 mL. 
• 
Repeat or unscheduled samples may be taken for safety reasons or for sampling 
issues. 
7.1. 
Gather Share Know Participant Hub 
The ‘Gather Share Know’ Participant Hub is an optional, web-based application with a 
patient facing solution will provide the following capability: 
• A guide/overview of Gather Share Know platform: information provided, how to 
use and potential benefits. 

T M F -1 3 8 5 5 5 4 1  
C O N FI D E N TI A L  
 
 
 
2 1 3 2 9 9  
 
Pr ot o c ol A m d 0 3  
 
3 9  
 
•  Patie nt Cre de ntials: F oll o wi n g c o m pleti o n of i nf or me d c o nse nt, patie nts will be 
pr o vi de d cre de ntials t o l o g i nt o t he Gat h er  S hare K n o w Partici pa nt H u b.  
•  I nf or mati o n a b o ut t he St u d y: St u d y Site a n d PI i nf or mati o n a n d st u d y pr o gress 
(e. g. e nr olle d, assess me nts, a vaila ble res ults, st u d y c o m plet e, etc.).  
•  St u d y Visits: List of visits a n d w hat t o e x pect f or eac h visit.  
•  E m be d de d a n d / or li n ke d e d ucati o nal materials fr o m cre di ble s o urces (e. g. 
Nati o nal Ca ncer I nstit ute) wit h i nf or mati o n s pecific t o patie nt’s dia g n osis: T his 
will be pr o vi de d b y G S K t o partici pa nt h u b ve n d or t o p o p ulate base d o n 
dia g n osis.  
•  La b orat or y res ults (e. g. v al i date d cli nical bi o mar k er data) i n si m ple, easil y 
u n derst o o d, la n g ua ge: Res ults will c o me fr o m t he la b ve n d or c o n d u cti n g t h e 
a nal ysis. F oll o wi n g a gree d p h ysici a n re vi e w peri o d, t his data will be p u blis he d t o 
partici pa nt h u b.  
•  Trial Matc hi n g: T he partici pa n t h u b ca n rec o m me n d G S K O nc ol o g y trials t hat 
patie nts mi g ht be eli gi ble f or base d o n t h e M D CI la b a n d bi o mar ker res ults a n d a 
s u bset of i ncl usi o n / e x cl usi o n criteria. I nf or mati o n a b o ut t hese trials a n d st u d y PI 
or staff c o nt acts will be pr o vi de d t o all o w patie nts t o f oll o w u p t o e x press i nterest. 
T hese patie nts c a n als o b e n otifie d as ne w G S K O nc ol o g y trials b ec o me a v aila ble 
w here t he y m a y be eli gi ble.  
List of G S K trials t o use f or matc hi n g a n d ass ociate d e nr ol me nt ti mi n gs will be 
pr o vi de d b y G S K a n d u p da te d acc or di n gl y o ver ti me. R ules f or trial matc hi n g 
base d o n bi o mar ker res ults a n d a s u bset of i ncl usi o n / e xcl usi o n criteria will be 
pr o vi de d. Bi o mar ker res ults will c o me fr o m la b ve n d or. Data t o assess a gai nst 
s u bset of i ncl usi o n / e x cl usi o n criteria will c o me fr o m I n F or m e C R F a n d w here 
a p plica ble, f urt her i nf or mati o n fr o m t he st u d y sit e pers o n nel. A n o utli ne of w hat 
data will be ret ur n e d t o p atie nts, as well as directi ves & res o urces f or c o u nselli n g, 
ca n be f o u n d i n t he S R M.  
7. 2.  
T u m or I m a gi n g  
I ma gi n g will be o btai ne d b y t he site a n d tra ns mitte d t o a ce ntr al i ma gi n g v e n d or f or 
a n al ys es. I nstr ucti o ns f or t u m or i ma gi n g a n d tr a ns missi o n t o t he ce ntr al 
i ma gi n g ve n d or are detaile d i n t he I m a gi n g M a n u al pr o vi de d t o i n vesti gati ve sites. 
7. 2. 1.  
I m a gi n g R el at e d t o Ar c hi v e d T u m or S a m pl e 
F or partici pa nts w h o pr o vi de arc hi ve d tiss ue s a m ples, ass ociate d i ma gi n g b y C T/ M RI 
t hat was ac q uir e d f or sta n dar d of care t u m or assess me nt wit hi n ± 4 wee ks of  bi o ps y will 
be c ollecte d, t o pair wit h t he tiss ue sa m ple . I m a ges t hat ca pt ure t he bi o psie d lesi o n a n d 
a n y ot h er areas of diseas e will be use d f or
researc h. Refer t o Secti o n 7. 2. 2  f or 
t he t y pes of i ma gi n g e x pecte d f or t his p ur p ose. 
7. 2. 2.  
Vi sit 2 I m a gi n g  
T u m or i ma gi n g m ust be c o m plete d at Visit 2 ± 4 wee ks ( 2 8 da ys). If fres h bi o ps y is 
perf or me d at Visit 2, i ma gi n g s h o ul d be c o m plete d pri or t o t he bi o ps y pr oce d ure, 
prefera bl y o n t he sa m e d a y, t o a v oi d p ossi ble ra di o gra p hic alterati o ns d ue t o tiss ue 
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sampling.  Imaging conducted prior to enrollment may be used if acquired within 4 
weeks of the visit and the requirements for tumor imaging are met. 
The below imaging requirements are designed to best align with possible GSK Intended 
Treatment Protocols in order to reduce the potential need for re-scanning within the 
subsequently enrolled treatment study. 
• 
Computed tomography (CT) scan with oral and/or IV contrast. 
Indication 
CT(1,2) Anatomical Coverage Required 
NSCLC, CRC or 
breast 
chest, abdomen, and pelvis 
HNSCC 
chest and abdomen, including liver 
head and neck region(3) 
Ovarian 
abdomen and pelvis 
(1) In cases where contrast-enhanced CT is contraindicated, magnetic resonance imaging 
(MRI) with IV gadolinium is acceptable. When a chest scan is required, a non-contrast 
CT of the chest is preferred over non-contrast MRI. 
(2) CT from a positron emission tomography (PET)-CT is permitted provided it is with CT 
contrast and is of diagnostic quality.  
(3) CT or MRI accepted per site standard procedure. 
 
• 
Contrast-enhanced CT or MRI of other sites of disease as indicated by the 
participant’s underlying disease, following site standard procedures. 
• 
Photography of any superficial skin lesions including a visible ruler. 
• 
If completed at the site for SOC, positron emission tomography (PET) 
imaging, including FDG or other radiotracers, should also be collected. PET 
is not required for this protocol.  
7.2.3. 
Imaging from Image-Guided Biopsy 
Participants who provide archived tissue samples:  
If the biopsy was performed under image guidance, images from the procedure will be 
collected, if available. Relevant modalities include CT, MRI, ultrasound, or medical 
photography. If images from the procedure are not available or if biopsy was not 
conducted under image guidance, an annotated image from a diagnostic CT/MRI may be 
requested, to identify the specific site of the biopsy. Additional detail is provided in the 
Imaging Manual.  
Participants who provide fresh tissue samples:  
It is preferred that all fresh tissue collection (Section 7.7.1) is performed under image 
guidance when clinically relevant. CT is the preferred modality for non-visible or non-
palpable lesions. MRI or ultrasound is also accepted as relevant per tumor type. When 
imaging is conducted for biopsy guidance, images will be collected. The biopsied lesion 
should be well identified either by a visible needle depicted on imaging or an annotation 
to denote the lesion with anatomical location clearly identified on the image. Further 
guidance is provided in the Imaging Manual.  

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7.2.4. 
Follow Up Imaging 
For participants who continue on the MDCI protocol for follow-up (Table 2) any imaging 
conducted for standard of care tumor assessment within ±8 weeks of each study visit will 
be collected. Disease assessment modalities may include imaging by CT, MRI, PET 
(FDG or other radiotracer), nuclear medicine, or plain radiography (Xray) and 
photography.  
Upon withdrawal/progression, imaging for tumor assessment conducted within 4 weeks 
prior to biopsy will be collected. Imaging conducted after biopsy will not be collected. If 
biopsy is conducted under image guidance, imaging from the biopsy procedure will be 
collected in accordance with Section 7.2.3.  
It is preferred that on-study biopsy (Section 7.7.1) is performed under image guidance 
when clinically relevant. CT is the preferred modality for non-visible or non-palpable 
lesions. MRI or ultrasound is also accepted as relevant per tumor type. When imaging is 
conducted for biopsy guidance, images will be collected. The biopsied lesion should be 
well identified either by a visible needle depicted on imaging or an annotation to denote 
the lesion with anatomical location clearly identified on the image. Further guidance is 
provided in the Imaging Manual.  
7.3. 
Efficacy Assessments 
Not Applicable. 
7.4. 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA (Section 1.3). 
7.4.1. 
Physical Examinations 
• 
A complete physical examination will include, at a minimum, assessments of the 
Skin, Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. 
Weight will also be measured and recorded in eDC. 
• 
A brief physical examination 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. 
• 
Any specific conditions should be recorded under Medical History. 
 
7.4.2. 
Vital Signs   
• 
Oral temperature, pulse rate, and blood pressure will be assessed. 
• 
Blood pressure and pulse measurements will be assessed with a completely 
automated device. Manual techniques will be used only if an automated device 
is not available. 

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• 
Blood pressure and pulse measurements should be preceded by at least 5 
minutes of rest for the participant in a quiet setting without distractions (e.g., 
television, cell phones). 
• 
Vital signs (to be taken before blood collection for laboratory tests) will consist 
of 1 pulse and 1 blood pressure measurement. The readings will be recorded on 
the CRF. 
 
7.4.3. 
Electrocardiograms 
All cardiac assessments will be performed locally.  
The following assessments will be conducted in order to monitor participant safety:  
Single 12-lead electrocardiogram (ECG) will be obtained as outlined in the SoA 
(see Section 1.3) using an ECG machine that automatically calculates the heart rate 
and measures PR, QRS, QT, and QTc intervals. ECG to be performed only at 
baseline and result to be entered into eCRF. An ECG done within 2 weeks of Visit 1 
is acceptable, if the patient has not had any cardiac event. 
 
7.4.4. 
Clinical Safety Laboratory Assessments 
Refer to Appendix 2 for the list of clinical laboratory tests to be performed and to the 
SoA for the timing and frequency.  
• 
The investigator must review the laboratory report, document this review, and 
record any clinically relevant changes occurring during the study in the AE 
section of the CRF. The laboratory reports must be filed with the source 
documents. Clinically significant abnormal laboratory findings are those which 
are not associated with the underlying disease, unless judged by the investigator 
to be more severe than expected for the participant's condition.  
• 
All laboratory tests with values considered clinically significantly abnormal 
during participation in the study should be repeated until the values return to 
normal or baseline or are no longer considered significantly abnormal by the 
investigator or medical monitor.  
• 
All protocol-required laboratory assessments, as defined in Appendix 2 must be 
conducted in accordance with the laboratory manual and the SoA.  

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7.5. 
Adverse Events and Serious Adverse Events 
The definitions of an AE or SAE can be found in Appendix 3. 
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, 
or the participant's legally authorized representative). 
The investigator and any qualified designees are responsible for detecting, documenting, 
and reporting events that meet the definition of an AE or SAE and remain responsible for 
following up AEs that are serious, considered related to the study, or that caused the 
participant to discontinue the study (see Section 6.1).  
7.5.1. 
Time Period and Frequency for Collecting AE and SAE 
Information 
• 
All SAEs will be collected from at the time points specified in the SoA (Section 
1.3). However, any SAEs assessed as related to study participation (e.g., 
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. 
• 
All AEs will be collected at the time points specified in the SoA (Section 1.3). 
• 
Medical occurrences that begin before the start of procedures but after obtaining 
informed consent will be recorded on the Medical History/Current Medical 
Conditions section of the case report form (CRF) not the AE section. 
• 
All SAEs will be recorded and reported to the sponsor or designee immediately 
and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 3. 
• 
The investigator will submit any updated SAE data to the sponsor within 
24 hours of it being available. 
• 
Investigators are not obligated to actively seek AEs or SAEs after the conclusion 
of the study participation. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has been discharged from the 
study, and he/she considers the event to be reasonably related to the study 
participation, the investigator must promptly notify the sponsor. 
7.5.2. 
Method of Detecting AEs and SAEs 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs.  Open-ended 
and non-leading verbal questioning of the participant is the preferred method to inquire 
about AE occurrence.  

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7.5.3. 
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, will be followed until the event is 
resolved, stabilized, otherwise explained, or the participant is lost to follow-up (as 
defined in Section 6.2). Further information on follow-up procedures is given in 
Appendix 3. 
7.5.4. 
Regulatory Reporting Requirements for SAEs 
• 
Prompt notification by the investigator to the sponsor of a SAE is essential so 
that legal obligations and ethical responsibilities towards the safety of 
participants and the safety of a study intervention under clinical investigation are 
met.  
• 
The sponsor has a legal responsibility to notify both the local regulatory 
authority and other regulatory agencies about the safety of a study intervention 
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. 
• 
For all studies except those utilizing medical devices 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 SAEs) 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. 
7.5.5. 
Pregnancy 
• 
If a pregnancy is reported, the investigator should inform GSK within 24 hours of 
learning of the pregnancy and should follow the procedures outlined in Appendix 4. 
• 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAE. 
7.5.6. 
Death Events 
For all deaths, whether or not they are considered SAEs, specific Death sections of the 
CRF will be required to be completed.  
The Death CRF is provided immediately after the occurrence or outcome of death is 
reported. Initial and follow-up reports regarding death must be completed within one 
week of when the death is reported.  

T M F -1 3 8 5 5 5 4 1  
C O N FI D E N TI A L  
 
 
 
2 1 3 2 9 9  
 
4 5  
 
C CI

T M F -1 3 8 5 5 5 4 1  
C O N FI D E N TI A L  
 
 
 
2 1 3 2 9 9  
 
Pr ot o c ol A m d 0 3  
 
4 6  
 
C CI

T M F -1 3 8 5 5 5 4 1  
C O N FI D E N TI A L  
 
 
 
2 1 3 2 9 9  
 
Pr ot o c ol A m d 0 3  
 
4 7  
 
C CI

T M F -1 3 8 5 5 5 4 1  
C O N FI D E N TI A L  
 
 
 
2 1 3 2 9 9  
 
Pr ot o c ol A m d 0 3  
 
4 8  
 
 
C CI

T M F -1 3 8 5 5 5 4 1  
C O N FI D E N TI A L  
 
 
 
2 1 3 2 9 9  
 
Pr ot o c ol A m d 0 3  
 
4 9  
 
8.  
S T A TI S TI C A L C O N SI D E R A TI O N S  
8. 1.  
St ati sti c al H y p ot h e s e s  
M D CI is a n
st u d y. N o H y p ot hesis will be teste d u n der t his st u d y.  
8. 2.  
S a m pl e Si z e D et er mi n ati o n  
Si nce M D CI d o es n ot ai m t o test a n y s pecific h y p ot hesis or a ns wer a n y p artic ular 
q uesti o n, t here is n o statistical re q uire me nt t o r eac h a s pecific n u m b er of sa m ples a n d 
patie nts. It is e x pecte d t o e nr oll 4 0 0 partici pa nts i n t his st u d y.  
8. 3.  
P o p ul ati o n s f or A n al y s e s  
T he f oll o wi n g p o p ul ati o ns are defi ne d:  
 
P o p ul ati o n  
D e s cri pti o n  
Scr e e ne d  
All p articip a nts w h o si g n t h e I C F  
E nr oll e d  
All p articip a nts w h o si g n t h e I C F a n d m e et i ncl usi o n/ excl usi o n 
crit eria  
I n eli gi bl e f or Tr e at m e nt Tri al 
All p articip a nts w h o d o n ot e nr ol ont o a G S K tr eat m e nt st u dy  
R a n d o miz ed  
N A  
S af ety  
All p articip a nts w h o ar e e nroll e d a n d pr ovi d ed a t u m or/bl o o d 
s a m pl e 
 
8. 4.  
St ati sti c al A n al y s e s  
Descri pti ve s u m mar y statistics of t he ke y e n d p oi nts/ mar kers (s uc h as t h ose c o nsi dere d 
f or patie nt selecti o n f or vari o us assets) will be ta b ulate d a n d w here rele va nt will be 
stratifie d b y k e y bas eli ne de m o gra p hic a n d cli nical characteristics.  
U ns u per vise d cl usteri n g base d o n e x pressi o n le vels or m utati o n calls will be perf or me d t o 
i de ntif y ca ncer s u bt y pes. T he i de ntifie d s u bt y p es will be c o m pare d wit h s u bt y pes f o u n d 
i n pre vi o us researc h, s u c h as T C G A ( T he Ca n cer Ge n o me Atlas). For a n y p he n ot y pic 
i nf or mati o n of i nterest i n t he dataset, s uc h as treat me nt o utc o me, t he e nric h me nt of 
p he n ot y p e i n eac h s u bt y p e will be e x a mi ne d.  
I n a d diti o n, c orrel ati ve a n d s u per vise d a n al ys es of m olec ular pr ofili n g d ata a n d ot her 
bi o mar ker dat a i n rel ati o n t o s pecific p he n ot y pes will be carri e d o ut via a p pr o priate 
u ni variate ( o ne mar ker at a ti me) a nal ysis met h o ds t o assess a n d/ or i de ntif y s pecific 
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markers for further investigation. A variety of multivariate statistical and machine 
learning methods may also be carried out to identify combinatorial signatures and 
generate insights of potential use for patient selection/stratification or enrichment and 
other purposes in ongoing and upcoming clinical projects. 
8.4.1. 
Safety Analyse(s) 
Adverse event (AE) data will be summarized overall and stratified by appropriate 
baseline & clinical characteristics (examples: gender, tumor type/grade/antigen 
expression, etc.).  These summaries will be categorized by frequency and proportion of 
total subjects.  All AEs will be coded using the standard MedDRA.   
8.4.2. 
Other Analyse(s) 
Demographic and baseline characteristics will be summarized by tumor type (i.e. 
NSCLC, HNSCC, breast, ovarian, CRC); and by clinical characteristics of interest to be 
described in a subsequent analysis plan. Medical history; history of cancer diagnosis and 
treatment; past and current medical conditions will be listed. 
Percentage of participants and investigators utilizing the portal systems. 
Results from single and multi-marker in vitro diagnostic assays will be summarized by 
tissue (i.e., tumor, blood) and tumor type.   
HLA-subtypes for HLA-A locus will be listed and summarized by tumor type. Separate 
summaries of HLA-A may be given by ethnicity. 
Number of participants who successfully provided a tumor sample will be summarized by 
tumor type. Separate summaries may be given by baseline demographics such as age and 
ethnicity. 
Number of participants who have been referred into a treatment trial will be summarized 
by tumor type and treatment trial. Separate summaries may be given by baseline 
demographics such as age and ethnicity. 
Treatment Patterns: Anti-cancer treatments received will be summarized for all 
participants stratified by tumor type and by line of therapy. 
Time to Next Treatment (TTNT): The length of time from the initiation of an anticancer 
therapy to the date that the next systemic anticancer therapy is initiated. When subsequent 
treatment is not received, patients should be censored at last known activity (e.g. last 
physician visit). 
Time to Progression (TTP): The length of time from the date the patient initiates an 
anticancer therapy to the date that a progression event or death due to progression is 
reported by the physician in the patient chart.  
Overall Survival (OS): This is defined as the interval of time between the date of 
treatment initiation and the date of death due to any cause. For participants who do not 

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die, time of death will be censored at the date of last contact. Death due to any cause will 
be included. 
8.5. 
Interim Analyses 
Due to the continuous nature of this study, there is no interim analysis phase. Data will be 
continuously monitored and analysed in real-time during the course of the study.  
8.6. 
Translational Research Committee 
The Translational Research Committee (TRC) charter will describe the procedures 
related to TRC operations in greater detail. 
8.7. 
Limitations 
Patient population sampled may not be generalizable or comparable to participants who 
enrol in treatment protocols. 
 

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9. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
9.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
9.1.1. 
Regulatory and Ethical Considerations 
• 
This study will be conducted in accordance with the protocol and with: 
• Consensus ethical principles derived from international guidelines 
including the Declaration of Helsinki and Council for International 
Organizations of Medical Sciences (CIOMS) International Ethical 
Guidelines 
• Applicable ICH Good Clinical Practice (GCP) Guidelines 
• Applicable laws and regulations 
• 
The protocol, protocol amendments, ICF, Investigator Brochure, and other 
relevant documents (e.g., advertisements) must be submitted to an IRB/IEC by 
the investigator and reviewed and approved by the IRB/IEC before the study is 
initiated.  
• 
Any amendments to the protocol will require IEC/IRB approval before 
implementation of changes made to the study design, except for changes 
necessary to eliminate an immediate hazard to study participants.  
• 
The investigator will be responsible for the following: 
• Providing written summaries of the status of the study to the IRB/IEC 
annually or more frequently in accordance with the requirements, policies, 
and procedures established by the IRB/EC 
• Notifying the IRB/IEC of SAE or other significant safety findings as 
required by IRB/IEC procedures 
• Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European 
regulation 536/2014 for clinical studies (if applicable), and all other 
applicable local regulations 
9.1.2. 
Financial Disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study. 

T M F -1 3 8 5 5 5 4 1  
C O N FI D E N TI A L  
 
 
 
2 1 3 2 9 9  
 
Pr ot o c ol A m d 0 3  
 
5 3  
 
9. 1. 3.  
I nf or m e d C o n s e nt Pr o c e s s 
•  
T he I n vesti gat or or his/ h er re prese nt at i ve will e x plai n t he nat ure of t h e st u d y t o 
t he partici pa nt or his/ her le gall y a ut h orize d re pres e ntati ve a n d a ns w er all 
q uesti o ns re gar di n g t he st u d y.  
•  
Partici pa nts m ust be i nf or me d t hat t heir partici p ati o n is v ol u ntar y.  Partici p a nts 
or t heir le gall y a ut h orize d re pres e ntati ve will be re q uire d t o si g n a state me nt of 
i nf or me d c o nse nt t hat meets t he re q uire m e nts of 2 1 C F R 5 0, l ocal re g ulati o ns, 
I C H g ui deli nes, Healt h I ns ura nce P ort a bilit y a n d Acc o u nta bilit y Act ( HI P A A) 
re q uire me nts, w h ere a p plica ble, a n d t he I R B/I E C or st u d y ce nter.  
•  
T he me dical r ec or d m ust i ncl u de a state me nt t hat writte n i nf or me d c o ns e nt was 
o btai ne d bef ore t he partici pa nt was e nr olle d i n t he st u d y a n d t he date o n w hic h 
t he writte n c o nse nt w as o btai ne d.  T he a ut h orize d pers o n o btai ni n g t h e inf or me d 
c o nse nt m ust als o si g n t h e I C F.  
•  
Partici pa nts m ust be re -c o nse nte d t o t he m ost c urre nt versi o n of t he I C F(s) 
d uri n g t heir p artici pati o n i n t he st u d y.  
•  
C o pies of t he I C F(s) m ust be pr o vi de d t o t he parti ci pa nt or t he partici pa nt’s 
le gall y a ut h orize d re pres e ntati ve.  
•  
Partici pa nts w h o are rescree ne d are re q uir e d t o si g n a ne w I C F.  
T he I C Fs ma y c o ntai n a se parat e secti o n t hat a d dresses t he use of re mai ni n g ma n dat or y 
sa m ples f or o pti o nal
res earc h i n acc or da nce wit h S O P-G S K F -4 1 0.  T he 
I n v esti gator or a ut h orize d desi g nee will e x plai n t o eac h p artici pa nt t he o bj ecti ves of t he 
researc h.  Partici pa nts will be t ol d t hat t he y are free t o ref use t o partici pate 
a n d ma y wit h dra w t heir c o nse nt at a n y ti me a n d f or a n y reas o n d uri n g t he st ora ge p eri o d.  
A se parate si g nat ure will be re q uir e d t o d oc u me nt a partici pa nt’s a gree me nt t o all o w a n y 
re mai ni n g s p eci me ns t o be use d f or
researc h.  Partici pa nts w h o decli ne t o 
partici pate will n ot pr o vi de t his se parate si g n at ure.  
9. 1. 4.  
D at a Pr ot e cti o n  
•  
Par tici pa nts will be assi g ne d a u ni q ue i de ntifier b y t he S p o ns or.  A n y p arti ci pa nt 
rec or ds or datasets t hat are tra nsferre d t o t he S p o ns or will c o ntai n t he i de ntifier 
o nl y; partici pa nt n a mes or a n y i nf or mati o n w hic h w o ul d ma ke t he partici p a nt 
i de ntifia ble will n ot be tra nsferre d.  
•  
T he partici pa nt m ust be i nf or me d t hat his/ her pers o nal st u d y -relate d d ata will be 
use d b y t h e S p o ns or i n acc or da n ce wit h l ocal data pr otecti o n la ws.  T he le vel of 
discl os ure m ust als o be e x plai ne d t o t he partici pa nt.  
•  
T he partici pa nt  m ust be i nf or me d t hat his/ her me dical rec or ds ma y be e x a mi ne d 
b y Cli nical Q ualit y Ass ura nce a u dit ors or ot her a ut h orize d pers o n nel a p p oi nte d 
b y t he S p o ns or, b y a p pr o priate I R B/I E C me m b ers, a n d b y i ns p ect ors fr o m 
re g ulat or y a ut h orities. 
 
C CI
C CI
C CI

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9.1.5. 
Committees Structure 
A Translational Research Committee (made up of both internal and external experts) has 
been formed around this protocol to meet quarterly to discuss protocol design, 
development, and status. 
9.1.6. 
Dissemination of Clinical Study Data 
• 
Where required by applicable regulatory requirements, an investigator signatory 
will be identified for the approval of the clinical study report.  The Investigator 
will be provided reasonable access to statistical tables, figures, and relevant 
reports and will have the opportunity to review the complete study results at a 
GSK site or other mutually-agreeable location. 
• 
GSK will also provide the Investigator with the standard report of the tumor 
biopsy results, and applicable clinical trials, from DNAseq and RNAseq analysis 
initially performed on tumor biopsy.  
• 
GSK will also provide a subset of CLIA-validated results back to participants 
through Gather Share Know Participant Hub. List of results that will be shared 
can be found in SRM. 
• 
The procedures and timing for public disclosure of the protocol and results 
summary and for development of a manuscript for publication for this study will 
be in accordance with GSK Policy. 
• 
GSK intends to make anonymized participant-level data from this trial available 
to external researchers for scientific analyses or to conduct further research that 
can help advance medical science or improve patient care.  This helps ensure the 
data provided by trial participants are used to maximum effect in the creation of 
knowledge and understanding. 
• 
A manuscript will be progressed for publication in the scientific literature if the 
results provide important scientific or medical knowledge. 
9.1.7. 
Data Quality Assurance 
• 
All participant data relating to the study will be recorded on eCRF unless 
transmitted to the Sponsor (or designee) electronically (e.g., laboratory data).  
The Investigator is responsible for verifying that data entries are accurate and 
correct by physically or electronically signing the eCRF.  
• 
The Investigator must maintain accurate documentation (source data) that 
supports the information entered in the eCRF.  
• 
The Investigator must permit study-related monitoring, audits, IRB/IEC review, 
and regulatory agency inspections and provide direct access to source data 
documents.  
• 
The Sponsor (or designee) is responsible for the data management of this study 
including quality checking of the data.  

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• 
The Sponsor assumes accountability for actions delegated to other individuals 
(e.g., Contract Research Organizations). 
• 
Monitoring details describing strategy (e.g., risk-based initiatives in operations 
and quality such as Risk Management and Mitigation Strategies and Analytical 
Risk-Based Monitoring), methods, responsibilities and requirements, including 
handling of noncompliance issues and monitoring techniques (central, remote, 
or on-site monitoring) are provided in the Monitoring Plan. 
• 
Study monitors will perform ongoing source data verification to confirm that 
data entered into the eCRF by authorized site personnel are accurate, complete, 
and verifiable from source documents; that the safety and rights of participants 
are being protected; and that the study is being conducted in accordance with the 
currently approved protocol and any other study agreements, ICH GCP, and all 
applicable regulatory requirements.  
• 
Records and documents, including signed ICF, pertaining to the conduct of this 
study must be retained by the Investigator for 25 years from the issue of the final 
Clinical Study Report (CSR)/ equivalent summary unless local regulations or 
institutional policies require a longer retention period.  No records may be 
destroyed during the retention period without the written approval of the 
Sponsor.  No records may be transferred to another location or party without 
written notification to the Sponsor.  
9.1.8. 
Source Documents 
• 
Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected.  Source documents are filed at the 
investigator’s site. 
• 
Data reported/entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be 
explained.  The Investigator may need to request previous medical records or 
transfer records, depending on the study.  Also, current medical records must be 
available. 
9.1.9. 
Study and Site Start and Closure 
GSK or its designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of GSK.  Study sites will be closed upon study 
completion.  A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed. 
The Investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or Investigator may include 
but are not limited to: 
• 
Failure of the Investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the Sponsor’s procedures, or GCP guidelines 

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• 
Inadequate recruitment of participants by the Investigator 
• 
Discontinuation of further study intervention development 
9.1.10. 
Publication Policy 
• 
The results of this study may be published or presented at scientific meetings.  If this 
is foreseen, the Investigator agrees to submit all manuscripts or abstracts to the 
Sponsor before submission.  This allows the Sponsor to protect proprietary 
information and to provide comments.  
• 
The Sponsor will comply with the requirements for publication of study results.  In 
accordance with standard editorial and ethical practice, the Sponsor will generally 
support publication of multicenter studies only in their entirety and not as individual 
site data.  In this case, a coordinating Investigator will be designated by mutual 
agreement. 
• 
Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements. 

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9.2. 
Appendix 2: Clinical Laboratory Tests 
• 
The tests detailed in Table 3 will be performed by the local laboratory.  
• 
Protocol-specific requirements for inclusion or exclusion of participants are 
detailed in Section 5 of the protocol. 
• 
Additional tests may be performed at any time during the study as determined 
necessary by the Investigator or required by local regulations. 
• 
Pregnancy testing (urine or serum as required by local regulations) should be 
conducted as indicated in the SoA (Section 1.3 ). 
• 
Pregnancy testing (urine or serum as required by local regulations) should be 
conducted throughout the time frame for female participant contraception in 
Section 5.1, Inclusion Criteria. 
• 
Additional serum or urine pregnancy tests may be performed, as determined 
necessary by the Investigator or required by local regulation, to establish the 
absence of pregnancy at any time during the participant’s participation in the 
study. 
 
Table 3 
Protocol-Required Safety Laboratory Assessments 
Laboratory 
Assessments 
Parameters 
Hematology 
Platelet Count  
RBC Indices: 
• 
MCV 
• 
MCH 
• 
Reticulocytes 
WBC count with 
Differential: 
• 
Neutrophils 
• 
Lymphocytes 
• 
Monocytes 
• 
Eosinophils 
• 
Basophils 
RBC Count 
Hemoglobin 
Hematocrit 
Coagulation 
INR, PT, and aPTT 
Other Tests 
• 
Highly sensitive serum or urine hCG pregnancy test (as needed for women 
of childbearing potential)a 
• 
HIV, HBV, HCV, HTLV, EBV, and syphilis (spirochete bacterium). 
Abbreviations: aPTT = activated partial thromboplastin time; EBV = Epstein Barr virus; HBV = hepatitis B 
virus; HCV = hepatitis C virus; eCRF = electronic case report form; HIV = human immunodeficiency 
virus; HTLV = human T-lymphotropic virus; INR = international normalized ratio; MCH = mean 
corpuscular hemoglobin; MCV = mean corpuscular volume; PT = prothrombin time; RBC = red blood 
cells; WBC = white blood cells.  
a. 
Local urine testing will be standard for the protocol unless serum testing is required by local regulation 
or IRB/IEC. 
Note: All study-required laboratory assessments listed on Table 3 will be performed by a local laboratory; 
The results of each test must be entered into the eCRF. 

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9.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
9.3.1. 
Definition of AE 
AE Definition 
• 
An AE is any untoward medical occurrence in a clinical study participant, 
temporally associated with the use of a study intervention, whether or not 
considered related to the study intervention. 
• 
NOTE: An AE can therefore be any unfavorable and unintended sign (including 
an abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a study intervention. 
 
Events Meeting the AE Definition 
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or 
urinalysis) or other safety assessments (e.g., ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (i.e., not 
related to progression of underlying disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as 
an AE/SAE unless it is an intentional overdose taken with possible suicidal/self-
harming intent. Such overdoses should be reported regardless of sequelae. 
 
Events NOT Meeting the AE Definition  
• 
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by 
the investigator to be more severe than expected for the participant’s condition. 
• 
The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition. 
• 
Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is the AE. 

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• 
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen. 
 
9.3.2. 
Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalization for signs/symptoms of the disease under study, 
death due to progression of disease). 
An SAE is defined as any untoward medical occurrence that, at any dose, meets one or 
more of the criteria listed: 
o Results in death 
o Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, 
which hypothetically might have caused death, if it were more severe. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
• In general, hospitalization signifies that the participant has been detained 
(usually involving at least an overnight stay) at the hospital or emergency ward 
for observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during 
hospitalization are AE. If a complication prolongs hospitalization or fulfills any 
other serious criteria, the event is serious. When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered 
serious. 
• Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE. 
Results in persistent or significant disability/incapacity 
• 
The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
• 
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (e.g. sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 

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Is a congenital anomaly/birth defect 
Other situations: 
• 
Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events 
should usually be considered serious. 
• 
Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse. 
9.3.3. 
Recording and Follow-Up of AE and SAE 
AE and SAE Recording 
• 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g. hospital progress notes, laboratory, and diagnostics reports) 
related to the event. 
• 
The investigator will then record all relevant AE/SAE information in the CRF. 
• 
It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to GSK in lieu of completion of the GSK /AE/SAE CRF page. 
• 
There may be instances when copies of medical records for certain cases are 
requested by GSK. In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to GSK. 
• 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories:  
• 
Mild: An event that is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities. 
• 
Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities. 
• 
Severe: An event that prevents normal everyday activities. An AE that is assessed 
as severe should not be confused with an SAE. Severe is a category utilized for 
rating the intensity of an event; and both AE and SAE can be assessed as severe. 

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An event is defined as ‘serious’ when it meets at least 1 of the predefined 
outcomes as described in the definition of an SAE, NOT when it is rated as severe. 
Other measures to evaluate AE and SAE may be utilized (e.g. National Cancer Institute 
Common Terminology Criteria for Adverse Events (NCI-CTCAE).   
 
Assessment of Causality 
• 
The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE. 
• 
A "reasonable possibility" of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out. 
• 
The investigator will use clinical judgment to determine the relationship. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated. 
• 
The investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment. 
• 
For each AE/SAE, the investigator must document in the medical notes that 
he/she has reviewed the AE/SAE and has provided an assessment of causality. 
• 
There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to GSK. However, it is very 
important that the investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to GSK. 
• 
The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 
Follow-up of AE and SAE 
• 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by GSK 
to elucidate the nature and/or causality of the AE or SAE as fully as possible. This 
may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other health care professionals. 
• 
If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide GSK with a copy of any post-
mortem findings including histopathology. 
• 
New or updated information will be recorded in the originally completed CRF. 

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• 
The investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information. 
9.3.4. 
Reporting of SAE to GSK 
SAE Reporting to GSK via Electronic Data Collection Tool 
• 
The primary mechanism for reporting SAE to GSK will be the electronic data 
collection tool. 
• 
If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours. 
• 
The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
• 
After the study is completed at a given site, the electronic data collection tool will 
be taken off-line to prevent the entry of new data or changes to existing data. 
• 
If a site receives a report of a new SAE from a study participant or receives 
updated data on a previously reported SAE after the electronic data collection tool 
has been taken off-line, then the site can report this information on a paper SAE 
form (see next section) or to the Medical Monitor by telephone. 
• 
Contacts for SAE reporting can be found in SRM. 
 
 

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9.4. 
Appendix 4: Contraceptive Guidance and Collection of 
Pregnancy Information 
9.4.1. 
Definitions: 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal 
unless permanently sterile (see below). 
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle 
cannot be confirmed before first dose of study intervention, additional evaluation should 
be considered. 
Women in the following categories are not considered WOCBP 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
• 
Documented hysterectomy 
• 
Documented bilateral salpingectomy 
• 
Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternate medical cause other 
than the above, (e.g., mullerian agenesis, androgen insensitivity), investigator 
discretion should be applied to determining study entry. 
Note: Documentation can come from the site personnel’s: review of the 
participant’s medical records, medical examination, or medical history interview. 
3. Postmenopausal female 
• 
A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause.  
• 
A high follicle stimulating hormone (FSH) level in the postmenopausal 
range may be used to confirm a postmenopausal state in women not 
using hormonal contraception or hormonal replacement therapy (HRT). 
However, in the absence of 12 months of amenorrhea, confirmation with 
more than one FSH measurement is required.  
• 
Females on HRT and whose menopausal status is in doubt will be required to 
use one of the non-estrogen hormonal highly effective contraception methods 
if they wish to continue their HRT during the study. Otherwise, they must 
discontinue HRT to allow confirmation of postmenopausal status before 
study enrolment. 
 

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9.4.2. 
Contraception Guidance: 
• 
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
• 
Highly Effective Methodsb That Have Low User Dependency  
• 
Implantable progestogen-only hormone contraception associated with inhibition of 
ovulationc 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS)c 
• 
Bilateral tubal occlusion 
• 
Vasectomized partner 
• 
Note: Vasectomized partner is a highly effective contraceptive method 
provided that the partner is the sole sexual partner of the woman of 
childbearing potential and the absence of sperm has been confirmed. If not, 
an additional highly effective method of contraception should be used. 
Spermatogenesis cycle is approximately 90 days. 
• 
Highly Effective Methodsb That Are User Dependent 
• 
Combined (estrogen- and progestogen-containing) hormonal contraception 
associated with inhibition of ovulationc 
• 
oral 
• 
intravaginal 
• 
transdermal 
• 
injectable 
• 
Progestogen-only hormone contraception associated with inhibition of ovulationc 
• 
oral 
• 
injectable 
• 
Sexual abstinence 
• 
Note: Sexual abstinence is considered a highly effective method only if 
defined as refraining from heterosexual intercourse during the entire period 
of risk associated with the study intervention. The reliability of sexual 
abstinence needs to be evaluated in relation to the duration of the study and 
the preferred and usual lifestyle of the participant 
a. Contraceptive use by women should be consistent with local regulations regarding the use of 
contraceptive methods for those participating in clinical studies. 
b. Failure rate of <1% per year when used consistently and correctly. Typical use failure rates differ 
from those when used consistently and correctly. 
c. 
Male condoms must be used in addition to hormonal contraception. If locally required, in 
accordance with Clinical Trial Facilitation Group (CTFG) guidelines, acceptable contraceptive 
methods are limited to those which inhibit ovulation as the primary mode of action. 
1. Note: Periodic abstinence (calendar, sympto-thermal, post-ovulation methods), withdrawal (coitus 
interruptus), spermicides only, and lactational amenorrhoea method (LAM) are not acceptable methods 
of contraception for this study. Male condom and female condom should not be used together (due to 
risk of failure with friction) 

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9.4.3. 
Collection of Pregnancy Information 
Female Participants who become pregnant 
• 
Investigator will collect pregnancy information on any female participant, who 
becomes pregnant while participating in this study.  
• 
The initial information will be recorded on the appropriate form and submitted to 
GSK within 24 hours of learning of a participant's pregnancy.  
• 
Participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow up information on participant and neonate, which will 
be forwarded to GSK Generally, follow-up will not be required for longer than 6 to 8 
weeks beyond the estimated delivery date.   
• 
Any termination of pregnancy will be reported, regardless of fetal status (presence or 
absence of anomalies) or indication for procedure.  
• 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be 
reported as an AE or SAE.  
• 
A spontaneous abortion (occurring at <22 weeks gestational age) or still birth 
(occurring at >22 weeks gestational age) is always considered to be an SAE and will 
be reported as such.  
• 
Any SAE occurring as a result of a post-study pregnancy which is considered 
reasonably related to the study intervention by the investigator, will be reported 
to GSK as described in Appendix 3. 
• 
While the investigator is not obligated to actively seek this information in former 
study participants, he or she may learn of an SAE through spontaneous reporting.  
Any female participant who becomes pregnant while participating   
• 
will discontinue study or be withdrawn from the study 

T M F -1 3 8 5 5 5 4 1  
C O N FI D E N TI A L  
 
 
 
2 1 3 2 9 9  
 
Pr ot o c ol A m d 0 3  
 
6 6  
 
9. 5.  
A p p e n di x 5: A b br e vi ati o n s a n d Tr a d e m ar k s  
A b bre vi ati o n  Defi niti o n or E x pl a n ati o n  
A C T  
A d o pti ve T -cell t hera p y 
A D M A  
As y m metrical Di met h yl ate d Ar gi ni ne  
A E  
A d verse e ve nt  
a P T T 
Acti vate d partial t hr o m b o plasti n ti me  
B R C A  
Breast ca n cer s us ce pti bilit y ge n e  
C A R  
C hi meric a nti ge n rece pt or  
C D 4  
Cl uster of differe ntiati o n 4  
C D 8  
Cl uster of differe ntiati o n 8  
C F R  
C o de of Fe d eral Re g ul ati o ns ( U S)  
C R C  
C ol orectal carci n o ma  
C R F  
Case re p ort f or m  
C T  
C o m p ute d t o m o gra p h y  
C T A  
Cli nical Testis A nti ge n  
ct D N A  
Circ ulati n g t u m or D N A  
C T L A -4  
C yt ot o xic t -l y m p h o c yt e-ass ociate d pr otei n 4  
D N A  
De o x yri b o n ucleic aci d  
E C G  
Electr ocar di o gra m(s)  
e C R F 
Electr o nic Case Re p ort F or m  
F F P E  
F or mali n -fi x e d, paraffi n -e m be d de d  
G S K  
Gla x o S mit h Kli ne  
H L A  
H u ma n le u k oc yte a nti ge n  
H R D  
H o m ol o g o us Rec o m bi nati o n Deficie nc y  
I B 
I n v esti gat or’s br o c h ure 
I C F 
I nf or me d c o ns e nt f or m 
I H C 
I m m u n o hist oc he mistr y 
L A G E -1a  
Ca ncer testis a nti ge n 2  
M A T C H  
M olec ular A n al ysis f or T hera p y C h oice  
M D CI  
M olec ular Disease C haracterizati o n I nitiati ve  
M E P 5 0  
Met h yl os o me pr otei n 5 0  
M M A  
M o n o met h ylar gi ni ne  
M R C L S  
M y x oi d r o u n d cell li p osarc o ma  
M RI  
Ma g n etic res o n a nce i ma gi n g  
N A  
N ot a p plica ble  
N CI  
Nati o nal Ca ncer I nstit ute  
N G S  
Ne xt Ge nerati o n Se q ue n ci n g  
N S C L C  
N o n -s mall cell l u n g ca n cer 
N P V  
Ne gati ve Pre dicti ve Val u e  
N Y -E S O -1  
Ne w Y or k es o p ha geal s q ua m o us cell carci n o ma 1  
P A R P  
P ol y (a de n osi ne di p h os p hate -ri b ose) p ol y m eras e 
P D -1  
Pr o gra m me d deat h pr ot ei n 1  
P D -L 1  
P D -1 li ga n d  
P D -L 2  
P D -1 li ga n d (a n ot her o n e)  
C CI
C CI

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C O N FI D E N TI A L  
 
 
 
2 1 3 2 9 9  
 
Pr ot o c ol A m d 0 3  
 
6 7  
 
A b bre vi ati o n  Defi niti o n or E x pl a n ati o n  
P K  
P har mac o ki netic(s)  
P P V  
P ositi ve Pre dicti ve Val ue  
P R  
Partial Res p o nse (i P R = P R base d o n i R E CI S T)  
P R M T  
Pr otei n ar gi ni ne met h yltra nsferase  
P V RI G  
P oli o vir us Rece pt or -relat e d I m m u n o gl o b uli n D o m ai n C o ntai ni n g 
R N A  
Ri b o n ucleic aci d  
S A E  
Seri o us a d verse e ve nt  
S D M A  
S y m m etrical Di met h yl Ar gi ni ne  
S N P  
Si n gle n ucle oti de p ol y m or p his m  
S o A  
Sc he d ule of acti vities  
S o C  
Sta n dar d of care  
S R M  
St u d y R efere nce Ma n ual  
S S  
S y n o vial Sarc o ma  
T C G A  
T he Ca ncer Ge n o me Atlas  
TI GI T  
T -cell i m m u n o gl o b uli n a n d i m m u n orece pt or t yr osi ne-base d i n hi biti o n 
m otif d o mai n  
 
 
W B C  
W hite bl o o d cell  
W E S  
W h ole e x o me se q ue nci n g  
W O C B P  
W o ma n of c hil d beari n g p ote ntial  
W T S  
W h ole tra nscri pt o me se q ue nci n g  
Tr a d e m ar k I nf or m ati o n  
Tr a d e m ark s of t h e Gl a x o S mit h Kli n e 
gr o u p of c o m p a ni e s  
 
Tr a d e m ark s n ot o w n e d by t h e 
Gl a x o S mit h Kli n e gr o u p of c o m p a ni es  
Zej ula  
 
N O N E  
 
 
C CI

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C O N FI D E N TI A L  
 
 
 
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Pr ot o c ol A m d 0 3  
 
6 8  
 
9. 6.  
A p p e n di x 6: Pr ot o c ol A m e n d m e nt Hi st or y  
T he Pr ot oc ol A me n d me nt S u m mar y of C ha n ges T a ble f or t he c urre nt a me n d me nt is 
l ocate d directl y b ef ore t he Ta ble of C o nte nts ( T O C). 
P R O T O C O L A M E N D M E N T S U M M A R Y O F C H A N G E S T A B L E  
D O C U M E N T HI S T O R Y  
List d at es of ori gi nal pr otocol a nd all a m en d m ents i n r ev ers e c hr o nol o gical or d er.  
D o c u m e nt  
D at e  
D N G N u m b er  
A m e n d m ent 0 2  
2 5 -N O V -2 0 2 0  
2 0 1 9 N 4 1 8 1 93 _ 0 2  
A m e n d m ent 0 1  
1 5 -J U N-2 0 2 0  
2 0 1 9 N 4 1 8 1 93 _ 0 1  
Ori gi nal Pr ot oc ol  
0 9 -M A R -2 0 2 0  
2 0 1 9 N 4 1 8 1 93 _ 0 0  
 
A me n d me nt 0 2  2 5 N O V 2 0 2 0  
O ver all R ati o n ale f or t he A me n d me nt:  T h e o v erall rati o nale f or t his a m e n d me nt is t o 
re m o ve u n necessar y sa m ple a n d data c ollecti o ns, clarif y rati o nale a n d c o n d uct of M D CI 
st u d y, e x pa n d t he eli gi bilit y criteria rel ate d t o t u m or t y pe, as well as arc hi v al tiss ue 
sa m ples; re m o vi n g t he o pti o n of a ma n dat or y fres h bi o ps y f or e nr oll me nt. T u m or 
i ma gi n g f or t his st u d y has als o bee n re vise d t o refl ect t his c ha n ge. St o ol a n d uri ne 
sa m ples w ere re m o ve d fr o m Sc he d ul e of Acti vities, t o better ali g n wit h 
o verall o bjecti ve of t he M D CI st u d y. Me dic al C hart Re vie w was als o re m o ve d fr o m 
pr ot oc ol, as it was deter mi ne d t o be d u plicati ve t o data alrea d y bei n g c oll ecte d o n st u d y. 
Clarificati o ns/ u p dates were als o pr o vi de d re gar di n g t he e x pecte d i m pacts of t his st u d y. 
U p dates t o t he I ntr o d ucti o n secti o n, as  well as t u m or t y pes i ncl u d e d, t o reflect G S K 
O nc ol o g y cli nical trials a n d de vel o p me nt u p dates, were als o i ncl u de d.  
C CI

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Section # and 
Name 
Description of Change 
Brief Rationale 
Protocol Title 
Updated 
Protocol Title updated for clarification 
1.1 Synopsis & 3 
Objectives 
Removal of objectives and 
clarifications made 
Addition of objective related to 
safety data collected 
Some objectives were redundant and 
could be incorporated into one.  
Inclusion of objective related to 
summarizing safety data 
1.3 Schedule of 
Activities 
Table 1: Removed Stool 
Table 1: Removed Urine (except 
for pregnancy) 
Table 1: Revised Biopsy 
requirement 
Table 2: Added Review of 
AEs/SAEs 
Table 1 changes: Simplifying of study 
conduct. 
 
Table 2 change: Because of 
procedures, Review of AEs/SAEs 
should be included 
5.1 Inclusion 
Criteria 
Revised sample acceptance & 
restrictions for tumor specimen 
To align with treatment trial protocols 
7.2 Tumor 
Imaging 
Removed retrospective image 
collection. 
Updated timing of image 
collection related to tumor 
sample. 
Alignment with tumor sample collection 
timing. 
7.2.1 Imaging 
Related to 
Archived Tumor 
Sample 
Added new section 
Updated the section as per revised 
biopsy requirement 
2 Introduction & 
Throughout 
Updated information & study 
schema, corrected 
inconsistencies and typos 
Removed Medical Chart Review 
Added risk associated with 
assays 
To improve quality of the protocol 
 
Amendment 01 15-JUN-2020 
Overall Rationale for the Amendment: The overall rationale for this amendment is the 
removal of two exclusion criteria (see table below), select local labs, and specific 
portions of the Medical Chart Review which are considered not applicable to the study 
population or the conduct of this study. Also, the primary objective related to the 

T M F -1 3 8 5 5 5 4 1  
C O N FI D E N TI A L  
 
 
 
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Pr ot o c ol A m d 0 3  
 
7 0  
 
de vel o p me nt a n d usa ge of t he partici pa nt h u b was c ha n ge d t o a n
o bjecti ve 
si nce t here is n o sci e ntific o ut p ut t o meas ure. A d diti o nal clarificati o ns were als o pr o vi de d 
re gar di n g p atie nt tra vel t o treat me nt sites, t he t otal n u m ber of partici pa nts, a n d details 
relate d t o t he e n d of st u d y.  
S e cti o n # a n d 
N a m e  
D e s cri pti o n of C h a n g e  
Bri ef R ati o n al e  
1. 1 Syn opsis &  
3. O bjectiv es a n d 
E n d poi nts  
M ov e d a n d r evise d th e Pri m ary 
O bj ectiv e r eg ar di ng th e 
p artici p a nt hu b to th e
O bj ectiv es secti o n  
N ot a sci entific o ut p ut of st u dy  
1. 1 Syn opsis  
S et th e n u m ber of p articip ants on 
st u dy to a p pr oxi m ately 4 00 
p artici p a nts.  
Pr evi o us pr ot ocol di d n ot provi d e a n 
ex act n u m b er  
1. 3 Sch ed ul e of 
Activiti es  
T a bl e 1: R e m ov ed ly m p hocyt e 
l oc al l a b r eq uir e m ent. 
T a bl e 2: R e m ov ed Qu esti onn aire  
N ot n ecess ary for t his stu dy p o pul ati on 
or st u dy co nd uct.  
Q u esti on n aire will n ot only b e li mit e d to 
p ati ents w ho m ov e o nto T abl e 2.  
4. 2 E n d of St u dy 
D efi niti o n  
P artici p a nt will b e d e t er mi ne d to 
h av e co m pl ete d th e stu dy up o n 
si g ni n g co ns ent to a n oth er G S K 
st u dy. 
D oc u m e nte d evi d e nc e of stu dy 
c o m pl eti o n. 
5. 1 Incl usi o n 
Crit eri a  
Cl arity a d d ed th at p atie nt 
tr av elli n g to a tr e at m ent c ent er 
c a n d o s o at discreti o n of 
p hysici a n.  
B as e d o n exter n al physici an f ee d back.  
5. 2 Exclusi o n 
Crit eri a  
R e m ov e d t wo Excl usi on Crit eria  
st ati n g, “ R e d bl o o d c ell 
tr a nsf usi on wit hi n 2 w eeks prior 
t o a ntici p ate d start of st u dy 
scr e e ni n g.” A n d 
“ A ntic o a g ul ati on”. 
Crit eria n ot a p plic abl e to t he st u dy 
p o pul ati on b ase d o n ext er nal p hysici a n 
a n d G S K m edic al m o nitor fe e db ack.  
8. 0 M edic al C h art 
R evi e w  
P arts of t he m e dic al ch art revi e w 
w er e r e m ov e d  
N o l o n ger a r eq uire m e nt f or t h e st u dy 
pr ot oc ol.  
9. 1 0. 4 R ep orti ng 
of S A E t o G S K  
R e m ov al of S A E r e p orti ng vi a 
p a per e C R F  
S t u dy will use el ectr o nic r e porti n g of 
S A Es  
T hr o u gh o ut  
C orr ect e d i nco nsist enci es an d 
ty p os 
T o i m pr ov e q u ality of t h e prot oc ol  
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10. 
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