A Phase 1, Multicentre, Open-Label, Dose-Escalation and Cohort Expansion Study of Niraparib and Dostarlimab in Paediatric Patients With Recurrent or Refractory Solid Tumours
Phase: PHASE1
Conditions: Neoplasms
Sponsor: GlaxoSmithKline

Protocol
Study ID: 213406
Study Official Title: A Phase 1, Multicentre, Open-Label, Dose-Escalation and 
Cohort Expansion Study of Niraparib and Dostarlimab in Paediatric Patients 
With Recurrent or Refractory Solid Tumours
NCT ID: NCT04544995
Date of Document for Master Record: 12 Dec 2024
Date of Document for Supplement A: 17 Dec 2024
Date of Document for Supplement B: 17 Dec 2024

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 1 of 213 
TITLE PAGE 
MASTER PROTOCOL 
Protocol Title: 
A PHASE 1, MULTICENTRE, OPEN-LABEL, DOSE 
ESCALATION AND COHORT EXPANSION 
STUDY OF NIRAPARIB AND DOSTARLIMAB IN 
PAEDIATRIC PATIENTS WITH RECURRENT OR 
REFRACTORY SOLID TUMOURS 
Protocol Number: 
213406 Amendment 05 
Compound Number or 
Name:  
Niraparib (GSK3985771), Dostarlimab 
(GSK4057190A) 
Brief Title: 
Dose Escalation and Cohort Expansion Study of 
Niraparib and Dostarlimab in Paediatric Participants 
With Solid Tumours 
Study Phase: 
Phase 1 
Sponsor Name and Legal 
Registered Address: 
 
 
 
Medical Monitor Name 
and Contact Information: 
GlaxoSmithKline Research & Development Limited  
79 New Oxford Street 
London 
WC1A 1DG 
United Kingdom 
 
Contact Information can be found in the local study 
contact information document 
Sponsor Signatory: 
 
Nidale Tarek, MD 
Senior Medical Director 
Synthetic Lethality, GSK 
Regulatory Agency 
Identifying Number(s): 
EudraCT Number: 2020‐002359‐39 
EU CT: 2024-511071-16 
Approval Date:  
12 Dec 2024 
Copyright 2024 the GSK group of companies. All rights reserved. Unauthorised copying 
or use of this information is prohibited. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 2 of 213 
PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Table 1: 
Document History 
Document 
Date 
Amendment 05 
12 Dec 2024 
Amendment 04 GBR-1 
08 August 2024 
Amendment 04 
23 May 2024 
Amendment 03 
20 July 2022 
Amendment 02 
23 November 2020 
Amendment 01 
16 October 2020 
Original Protocol 
12 May 2020 
Amendment 05 (12 Dec 2024) 
Overall rationale for the current Amendment:  
Protocol Amendment 05 is a substantial amendment that aligns Protocol Amendment 04 
with all aspects of the UK-specific Protocol Amendment 04 GBR-1, resulting in a single 
global amendment. Additional changes include an update of the sponsor’s legal registered 
address plus administrative and editorial updates and clarifications for study conduct. 
A general description and brief rationale(s) for key changes are provided in the Table 2 
below. The synopsis was also updated to align with the changes in the protocol body, 
where applicable. 
Table 2 
List of main changes in the protocol and their rationale: 
Section # and title 
Description of change 
Brief rationale 
Title Page 
Sponsor legal address update 
To align with current GSK policy 
Section 1.1 Synopsis 
Methodology Part 1B Design 
 
Section 4.1.2 Part 1B Design 
 
Section 11 APPENDIX 1. 
REGULATORY, ETHICAL, AND 
Language updated to indicate that 
the dose escalation committee 
(DEC) will review safety data and 
will determine the 
niraparib/dostarlimab dosing 
strategy 
To more clearly describe the role of 
the DEC in the dose escalation 
decision-making process overall 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 3 of 213 
Section # and title 
Description of change 
Brief rationale 
STUDY CONSIDERATIONS 
Committees Structure 
Section 1.1 Synopsis 
Main Criteria for Inclusion; Section 
5.1 Participant Inclusion Criteria 
Point 03 
Addition of relevant time point (“at 
screening”) and of lesion type to 
be assessed 
To clearly indicate at what point in the 
study disease characteristics were to 
be evaluated and to describe exactly 
what type of lesions were to be 
tracked 
Section 1.1 Synopsis 
Main Criteria for Exclusion; Section 
5.2 Participant Exclusion Criteria 
Point 15 
Participant has not recovered (i.e., 
to Grade ≤1 or to baseline) from 
prior systemic anticancer therapy-
induced AEs. Note: Participants 
with alopecia, hearing impairment, 
Grade ≤2 neuropathy, Grade ≤2 
fatigue, Grade ≤2 anaemia, and/or 
Grade ≤2 neutropenia are an 
exception to this criterion and may 
qualify for participation in the 
study . 
To revert the wording to that in 
Protocol Amendment 04, which 
provided more specific criteria for 
enrollment of participants with 
ongoing toxicities.   
Section 1.3 Schedule of Activities 
(SoA) 
Footnote x 
“Cycle 1 Day 1 2.5 hour samples 
must be collected at the 
scheduled time ±0.5 hour” was 
added 
To more specifically define the 
permitted sample collection window 
Section 1.3 Table 3 Schedule of 
Activities 
Table 4 Tumor Assessment 
Flowchart 
Addition of text indicating bone 
marrow evaluation is required for 
all participants to confirm 
response. 
To clarify timing of required bone 
marrow assessments during 
response evaluation 
Section 4.7.2.2 Dostarlimab 
Addition of extensive text on 
recognition and management of 
immune-mediated AE related to 
dostarlimab 
To update and further clarify 
information around toxicities 
associated with dostarlimab treatment  
Section 4.7.2.2. Dostarlimab and 
Table 10 Renal failure or nephritis 
Addition of treatment 
recommendation for Grade 3-4 
renal failure or nephritis 
To provide additional guidance for 
specific immune-mediated toxicity 
management  
Section 6.8.2 Prohibited Medications 
Text was updated with new 
information particularly with 
respect to drug-drug interactions 
To provide up-to-date information to 
investigators for use of niraparib by 
participants taking concomitant 
therapies  
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 4 of 213 
Section # and title 
Description of change 
Brief rationale 
Section 8.3.1 Time Period and 
Frequency for Collecting AE and 
SAE Information 
Guidance for recording and 
reporting SAE information after 
participant is no longer in the 
study was added 
To provide more comprehensive 
directions for SAE reporting 
Section 8.4.1 PK Sample Collection  
Text about analysis of collected 
PK samples was added 
To provide clarity on conditions under 
which PK sample analysis may 
proceed 
Section 11 APPENDIX 1. 
REGULATORY, ETHICAL, AND 
STUDY CONSIDERATIONS 
Committee Structure Early Safety 
Data Review AND/OR Committee 
The text “Part 2 Safety Run-in” 
was added 
To clarify that the Dose Escalation 
Committee would review and 
consider data from both Part 1 and 
Part 2 Safety Run-in. 
Section 11 APPENDIX 1. 
REGULATORY, ETHICAL, AND 
STUDY CONSIDERATIONS Source 
Documents 
Examples were added of 
contracted third parties and of 
possible source data that could be 
shared with these third parties 
To provide further clarification about 
the types of individuals who 
potentially might have access to and 
review source data and the types of 
source data that might be reviewed 
Section 11 APPENDIX 4 
GUIDELINES FOR ASSESSMENT 
OF DISEASE, DISEASE 
PROGRESSION AND RESPONSE 
CRITERIA – ADAPTED FROM 
RECIST 1.1 
Text about non-measurable 
disease was removed as well as 
text about no target lesions at 
baseline and Table 19   
To align text with the protocol 
requirements that participants must 
have measurable/evaluable disease 
at baseline to be eligible.  
Section 11 APPENDIX 4 
GUIDELINES FOR ASSESSMENT 
OF DISEASE, DISEASE 
PROGRESSION AND RESPONSE 
CRITERIA – ADAPTED FROM 
RECIST 1.1 
Text about confirmation criteria 
were updated 
To clarify the need for confirmation of 
PR or CR and to direct reader to 
Table 4 for additional guidance.  
Section 11 APPENDIX 5 
GUIDELINES FOR ASSESSMENT 
OF DISEASE, DISEASE 
PROGRESSION AND RESPONSE 
CRITERIA IN PARTICIPANTS WITH 
NEUROBLASTOMA – ADAPTED 
FROM REVISED INTERNATIONAL 
NEUROBLASTOMA RESPONSE 
CRITERIA (INRC) 
Text about confirmation of 
responses was added 
To provide guidance on timing of 
confirmatory scans and to direct 
reader to Table 4 for additional 
instructions. 
Section 11 APPENDIX 8 LIVER 
SAFETY:  REQUIRED ACTIONS, 
MONITORING, AND FOLLOW-UP 
TO ASSESS CAUSALITY OF LIVER 
EVENT 
Text for follow-up needed to 
assess causality was updated to 
read:  Blood and serum sample for 
PK analysis of niraparib 
and dostarlimab, respectively, 
To clarify steps required for 
acceptable follow-up of liver 
toxicity/event 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 5 of 213 
Section # and title 
Description of change 
Brief rationale 
obtained within 144 hours after 
last dose of study intervention5 
Throughout document 
Minor corrections and formatting 
adjustments were made 
To add clarification and increase 
readability 
 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 6 of 213 
TABLE OF CONTENTS 
1. 
PROTOCOL SUMMARY ........................................................................................ 12 
1.1. 
Synopsis ..................................................................................................... 12 
1.2. 
Schemas..................................................................................................... 30 
1.3. 
Schedule of Activities (SoA) ........................................................................ 32 
2. 
INTRODUCTION .................................................................................................... 43 
2.1. 
Background on Niraparib ............................................................................ 43 
2.1.1. 
Clinical Data for Niraparib ............................................................ 43 
2.2. 
Background on Dostarlimab ........................................................................ 44 
2.2.1. 
Clinical Data for Dostarlimab ........................................................ 44 
2.3. 
Rationale for Synergy Between PARP Inhibitors and Immune 
Checkpoint Inhibitors .................................................................................. 45 
2.4. 
Rationale for Tumour Type ......................................................................... 46 
2.5. 
Rationale for Current Study ........................................................................ 46 
2.6. 
Benefit Risk Assessment ............................................................................ 47 
2.6.1. 
Risk Assessment: ........................................................................ 47 
2.6.2. 
Overall Benefit: Risk Conclusion .................................................. 51 
2.6.3. 
Dose Justification ......................................................................... 51 
3. 
STUDY OBJECTIVES AND ENDPOINTS .............................................................. 55 
4. 
OVERALL DESIGN ................................................................................................ 57 
4.1. 
Part 1 Dose Escalation Design ................................................................... 57 
4.1.1. 
Part 1A Design ............................................................................ 58 
4.1.2. 
Part 1B Design ............................................................................ 61 
4.2. 
Intra-Participant Dose Escalation ................................................................ 65 
4.3. 
Dose Limiting Toxicity ................................................................................. 65 
4.4. 
General Study Conduct ............................................................................... 66 
4.5. 
Number of Participants ............................................................................... 69 
4.6. 
Treatment Assignment ................................................................................ 69 
4.7. 
Dose Adjustment Criteria ............................................................................ 70 
4.7.1. 
Niraparib Dose Adjustment for Age and Weight ........................... 70 
4.7.2. 
Dose Adjustment for Adverse Events ........................................... 70 
4.8. 
End of Study Definition ............................................................................... 86 
4.9. 
Study Conduct ............................................................................................ 86 
4.9.1. 
Procedures by Visit ...................................................................... 86 
4.9.2. 
General Guidance for Treatment Continuity when 
Participants are Unable to Come into the Clinic ........................... 86 
5. 
STUDY POPULATION ........................................................................................... 88 
5.1. 
Participant Inclusion Criteria ....................................................................... 88 
5.2. 
Participant Exclusion Criteria ...................................................................... 90 
5.3. 
Lifestyle Considerations .............................................................................. 93 
5.4. 
Screen Failures........................................................................................... 93 
6. 
STUDY TREATMENTS(S) AND CONCOMITANT THERAPY ................................ 94 
6.1. 
Study Treatment(s) Administered ............................................................... 94 
6.2. 
Preparation/Handling/Storage/Accountability .............................................. 96 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 7 of 213 
6.2.1. 
Study Treatment Packaging and Labelling ................................... 96 
6.2.2. 
Study Treatment Storage ............................................................. 96 
6.2.3. 
Administration .............................................................................. 96 
6.2.4. 
Study Treatment Accountability ................................................... 97 
6.2.5. 
Study Treatment Handling and Disposal ...................................... 97 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................... 98 
6.4. 
Study Treatment Compliance ...................................................................... 98 
6.5. 
Dose Modification ....................................................................................... 98 
6.6. 
Treatment of Overdose ............................................................................... 98 
6.7. 
Continued Access to Study Intervention After the End of the Study ............ 99 
6.8. 
Concomitant Therapy.................................................................................. 99 
6.8.1. 
Rescue Medications .................................................................... 99 
6.8.2. 
Prohibited Medications ................................................................. 99 
6.8.3. 
Other Study Restrictions ............................................................ 102 
7. 
DISCONTINUATION OF STUDY TREATMENT AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ................................................................... 103 
7.1. 
Discontinuation of Study Treatment .......................................................... 103 
7.1.1. 
Liver Chemistry Stopping Criteria .............................................. 104 
7.1.2. 
QTc Stopping Criteria ................................................................ 105 
7.2. 
Withdrawal of Consent .............................................................................. 106 
7.3. 
Participant Discontinuation/Withdrawal from the Clinical Study ................. 106 
7.4. 
Lost to Follow-Up ...................................................................................... 107 
8. 
STUDY ASSESSMENTS AND PROCEDURES ................................................... 108 
8.1. 
Assessment of Efficacy ............................................................................. 108 
8.1.1. 
Primary Efficacy Endpoint .......................................................... 108 
8.1.2. 
Secondary Efficacy Endpoints ................................................... 108 
8.2. 
Assessment of Safety ............................................................................... 110 
8.2.1. 
Safety Parameters ..................................................................... 111 
8.2.2. 
Demographic/Medical History .................................................... 111 
8.2.3. 
Disease History.......................................................................... 111 
8.2.4. 
Medical and Surgical History...................................................... 111 
8.2.5. 
Electrocardiogram ...................................................................... 112 
............................................... 112 
8.2.7. 
Physical Examination ................................................................. 112 
8.2.8. 
Vital Signs, Height, and Weight .................................................. 112 
8.2.9. 
Pregnancy Testing ..................................................................... 112 
8.2.10. 
Performance Status ................................................................... 113 
8.2.11. 
Psychological Assessments ....................................................... 113 
8.2.12. 
Laboratory Assessments ........................................................... 113 
8.2.13. 
Drug Screen .............................................................................. 114 
8.2.14. 
Viral Disease Testing ................................................................. 114 
8.3. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and Other 
Safety Reporting ....................................................................................... 115 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE 
Information ................................................................................. 115 
8.3.2. 
Method of Detecting AEs and SAEs ........................................... 115 
8.3.3. 
Follow-Up of AEs and SAEs ...................................................... 116 
8.3.4. 
Regulatory Reporting Requirements for SAEs ........................... 116 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 8 of 213 
8.3.5. 
Pregnancy ................................................................................. 116 
8.3.6. 
Adverse Events of Special Interest (AESI) ................................. 117 
8.4. 
Pharmacokinetics, Immunogenicity, and Biomarkers ................................ 117 
8.4.1. 
PK Sample Collection ................................................................ 118 
8.4.2. 
Immunogenicity Sample Collection ............................................ 118 
............................................................ 118 
............................................................ 119 
8.6. 
Health Economics ..................................................................................... 119 
9. 
STATISTICAL CONSIDERATIONS ...................................................................... 120 
9.1. 
Sample Size Determination ...................................................................... 120 
9.2. 
Analysis Populations ................................................................................. 120 
9.3. 
Statistical Analyses ................................................................................... 121 
9.3.1. 
General Considerations ............................................................. 122 
9.3.2. 
Primary Endpoints ..................................................................... 122 
9.3.3. 
Secondary Endpoints ................................................................. 122 
9.3.4. 
Exploratory Endpoints ................................................................ 124 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................. 125 
11. APPENDICES ...................................................................................................... 126 
12. REFERENCES ..................................................................................................... 203 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 9 of 213 
LIST OF TABLES 
Table 1: 
Document History ..................................................................................... 2 
Table 2 
List of main changes in the protocol and their rationale: ........................... 2 
Table 3: 
Schedule of Activities ............................................................................. 33 
Table 4: 
Tumour Assessment Flowchart .............................................................. 41 
Table 5: 
Summary of Risks and Mitigations for Niraparib ..................................... 48 
Table 6: 
Summary of Risks and Mitigations for Dostarlimab ................................ 49 
............... 53 
Table 8: 
Objectives and Endpoints for Study 213406 ........................................... 55 
Table 9: 
Niraparib Dose Modifications for Nonhaematologic Adverse 
Reactions ............................................................................................... 71 
Table 10: 
Niraparib Dose Modifications for Haematologic Adverse 
Reactions ............................................................................................... 72 
Table 11: 
Guidelines for Treatment of Immune-mediated Adverse Events ............. 75 
Table 12: 
Infusion Reaction Treatment Guidelines ...................................................... 84 
Table 13: 
Investigational Products ......................................................................... 95 
Table 14: 
Bundle Branch Block QTc Discontinuation Criteria .................................... 106 
Table 15: 
Safety Laboratory Assessments ........................................................... 114 
Table 16: 
Analysis Sets ....................................................................................... 121 
Table 17: 
Contraceptives Allowed During the Study............................................. 140 
Table 18: 
Evaluation of Overall Response for Participants with Measurable 
Disease at Baseline ............................................................................. 147 
Table 19: 
Primary (Soft Tissue) Tumour Response a ........................................... 150 
Table 20: 
Tumour Response at Metastatic Soft Tissue and Bone Sites ............... 151 
Table 21: 
Metastatic Bone Marrow Disease ......................................................... 152 
Table 22: 
Evaluation of Overall Response ........................................................... 152 
Table 23: 
Abbreviations and Specialist Terms ..................................................... 154 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 10 of 213 
Table 24: 
Required actions, monitoring, and follow-up to assess causality 
of liver event ......................................................................................... 162 
Table 25: 
Liver Safety: Liver Chemistry Increased Monitoring Criteria with 
Continued Therapy ............................................................................... 164 
Table 26: 
mTPI-2 Decision Spreadsheet .............................................................. 169 
Table 27: 
HBV Schedule of Activities ................................................................... 172 
....... 173 
 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 11 of 213 
LIST OF FIGURES 
......................................................................... 30 
......................................................................... 31 
......................................................................... 59 
Figure 4: 
Part 1B Study Schema Under Protocol Amendment 03 (or 
Earlier) ................................................................................................... 61 
...................... 62 
Figure 6: 
Phase I/II Liver Chemistry Stopping and Monitoring Event 
Algorithm .............................................................................................. 105 
 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 12 of 213 
1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Name of Sponsor/Company: GlaxoSmithKline 
Name of Investigational Product: Niraparib, dostarlimab 
Name of Active Ingredient: Niraparib, dostarlimab 
Title of Study: A Phase 1, Multicentre, Open-label, Dose escalation and Cohort Expansion 
Study of Niraparib and Dostarlimab in Paediatric Patients with Recurrent or Refractory Solid 
Tumours 
Study Centre(s): Multicentre  
 
Phase of 
development:  
Phase 1 
Objectives: 
The following are the objectives for Part 1 of this study. The objectives for Part 2 of this study 
will be presented in each cohort-specific supplement, as applicable. 
Primary: 
The primary objectives for Part 1 of this study are as follows: 
• 
Part 1A: to establish the recommended Phase 2 dose (RP2D) of the combination of 
niraparib tablet and dostarlimab in paediatric participants 
• 
Part 1B: to establish the RP2D of the combination 
 
 in paediatric participants 
Secondary: 
The secondary objectives for Part 1 of this study are as follows: 
• 
to evaluate additional measures of anticancer activity (including objective response rate 
[ORR] and duration of response [DOR]) in paediatric participants 
• 
to evaluate the safety and tolerability of the combination of 
 
 in paediatric participants 
• 
to characterise the pharmacokinetics (PK) of the combination of niraparib and 
dostarlimab in paediatric participants 
• 
to assess the immunogenicity of dostarlimab in paediatric participants 
• 
 
 
Scope of Master Protocol: 
This is a master protocol (213406) consisting of the core protocol and the study design for Part 
1. The study design and endpoints for Part 2 of this study are outlined in separate cohort-
specific supplements; namely: 
CCI
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 13 of 213 
• 
Safety Run-in: Cohort of both osteosarcoma and neuroblastoma participants to assess 
the safety and tolerability of the 
 
 by assessing dose limiting toxicity (DLT) events and Grade ≥3 
thrombocytopenia adverse events (AEs).  
• 
Supplement A: Expansion Cohort of participants with osteosarcoma to assess the 
antitumour activity of the combination of niraparib and dostarlimab, as determined 
primarily by the progression-free survival rate at 6 months using Response Evaluation 
Criteria in Solid Tumours (RECIST) v1.1. 
• 
Supplement B: Expansion Cohort of participants with neuroblastoma to assess the 
antitumour activity of the combination of niraparib and dostarlimab, as determined 
primarily by ORR using International Neuroblastoma Response Criteria (INRC). 
Methodology:  
This is a Phase 1, multicentre, open-label, dose escalation study (Part 1) with a Safety Run-in 
and Cohort Expansion component (Part 2) (see Figure 1). The study will consist of an initial 
dose escalation portion conducted in participants with 
 
 
 
 
Part 1A, a dose escalation to determine the RP2D of the combination of 
 
, included participants who were able to swallow the 
 and 
who had a body weight of ≥20 kg. Part 1B, a dose escalation to determine the RP2D of the 
combination of 
, under Protocol Amendment 03 (or earlier), 
included participants who could not swallow 
 or who had a body 
weight of <20 kg. Part 1B under Protocol Amendment 05 will include participants who are <8 
years of age and will receive a modified 
. In Part 2 of the 
study under Protocol Amendment 03, the RP2D regimen established in Part 1A of the study 
was evaluated for efficacy and safety in disease-specific expansion cohorts. Part 2 under 
Protocol Amendment 05 will include participants who are ≥8 years old. In Part 2, a Safety 
Run-in evaluating a 
 will be conducted prior to potential 
further enrolment into disease-specific expansion cohorts, as outlined in the specific 
supplements. 
Part 1 Dose Escalation Design 
 
 
 
 
 
 
 
 
 
 
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 14 of 213 
 
 
 
 
Part 1A Design 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
Participants in Cohort 0 were dosed in a staggered fashion. At this dose level, no more than 
3 participants were allowed to receive an initial dose of study treatment until the first 3 
participants had all completed at least 1 cycle of study treatment and the resulting data from all 
3 participants had been reviewed. This was to ensure an adequate interval for observation and 
assessment of potential acute AE. Although not needed, dosing strategy for subsequent 
participants after the initial 3 participants dosed was to have been made by the Dose Escalation 
Committee (DEC) if >1 DLT was observed in the first 3 participants within the first cycle of 
treatment (see Appendix 1 for details regarding the DEC). 
If Cohort 0 
 was deemed safe based on the 
mTPI-2 parameters described above, 2 cohorts were to have opened: Cohort 1A and Cohort 
1B. If both Cohorts 1A and 1B were considered safe, then Cohort 2 
 
 was to be opened. If the Cohort 2 dose level was deemed 
safe, this may have been considered the RP2D for the niraparib tablet formulation. If the dose 
level from Cohort 2 was not cleared for use, the RP2D was to be the dose level from Cohort 
1B. If only 1 cohort of Cohorts 1A and 1B was deemed safe, then that dose level was to be 
considered the RP2D. Lastly, if neither Cohort 1A nor 1B was deemed safe, the combination 
dose level from Cohort 0 was to be the RP2D. 
Part 1A Cohort 0, Cohort 1A, and Cohort 1B were evaluated. Cohort 1B was not cleared; 
therefore, no participants were enrolled into Cohort 2. Further details regarding cohorts and 
RP2D determination are outlined in Section 4 of the protocol. 
The original RP2D of niraparib and dostarlimab was established for the niraparib tablet 
formulation in Part 1A. Part 2 (disease-specific expansion cohorts, as described in cohort-
CCI
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 15 of 213 
specific supplements to this protocol) was opened to accrual for a limited number of 
participants who were able to swallow the 
. In addition, Part 1B was 
opened once the RP2D was established in Part 1A and the niraparib TfOS was available.  
See Figure 2 for a schema of the Part1A study design. 
Part 1B Design 
Previously, under Protocol Amendment 03 (or earlier), in Part 1B 
 
 
 
 
 
 
  
Originally under Protocol Amendment 03, 3 participants were dosed in Part 1B Cohort 1; 
however, enrolment in Part 1B Cohort 1 was paused to investigate incidences of Grade 3 and 
Grade 4 thrombocytopenia observed in participants in Part 1B and in the Part 2 Neuroblastoma 
Cohort Expansion, and the original Part 1B portion of the study did not advance past Cohort 1. 
Following review and analysis of clinical, safety, and PK data for all study participants, 
 described in 
Section 2.6.3.1 and Table 7.  
Under Protocol Amendment 05, in Part 1B 
 the starting dose 
level for dostarlimab (DL1) will be the RP2D as determined from Part 1A 
 
, and the starting dose level for niraparib is outlined in Section 2.6.3.1of the 
protocol (and Section 4.1.2 and Figure 5). 
Under Protocol Amendments 04 and 05, the study design for Part 1B has been updated as 
shown in Figure 5. PK evaluations will be performed in at least 6 participants in each cohort 
unless enrolment into the cohort is closed prematurely due to toxicity. 
Enrolment into each Part 1B cohort will take participant age into consideration, with the intent 
to distribute enrolment across 3 age categories: 6 months to <2 years; ≥2 years to <6 years; and 
≥6 years to <8 years. Enrolment into each cohort will be limited to no more than 4 participants 
aged 6 years or older out of the first 6 participants. The remaining 2 participants out of the first 
6 participants in each cohort must be younger than 6 years.  
Once enrolment into Cohort A has reached the target 6 participants (or 8, if necessary), safety 
and PK data will be evaluated and the DEC will decide to open either Cohort B or Cohort C or 
to declare the Cohort A dose to be the RP2D. Decision steps are described below.  
If Cohort B is to be opened, but at least 1 participant from the youngest age category (6 months 
to <2 years) has not been enrolled in Cohort A, the first potential participant aged 6 months to 
<2 years to join the study will be enrolled into Cohort A to permit safety evaluation of the 
starting niraparib and dostarlimab dose levels. Data from this ≥6 months to <2 years of age 
participant will not contribute to the decision for the next dose level, but may be used to 
evaluate safety and PK within the age category. 
CCI
CCI
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 16 of 213 
The DEC will review all relevant safety and PK data immediately after all participants treated 
in the same dose cohort have passed the DLT period and determine the dosing strategy for 
subsequent participants. 
Cohort A 
Participants in Cohort A will be dosed in a staggered fashion, meaning no more than 
2 participants will be allowed to receive the initial dose of study treatment until each 
participant has completed 2 cycles of study treatment and the clinical safety data from both 
participants have been reviewed. This is to ensure an adequate interval for observation and 
assessment of tolerability of the dose.  
• 
If DLTs or Grade ≥3 thrombocytopenia are observed in ≤1 of the first 2 dosed participants 
and it is deemed safe to proceed by the study team, a third participant will be allowed to 
receive the initial dose of study treatment. No additional participants will be allowed to 
receive study treatment until the third participant has completed at least 2 cycles of study 
treatment and the resulting data have been reviewed by the study team. 
• 
If DLTs or Grade ≥3 thrombocytopenia are observed in <2 of the first 3 dosed 
participants, Cohort A will continue to enrol up to 6 evaluable participants. If a DLT is 
observed in 2 of the first 6 dosed participants, Cohort A will be expanded to 8 DLT-
evaluable participants.  
• 
If DLTs or Grade ≥3 thrombocytopenia are observed in both of the first 2 dosed 
participants, Part 1B will be paused. Safety data for the first 2 dosed participants will be 
reviewed by the DEC. The dosing strategy for subsequent participants will be determined 
by the DEC. (See Appendix 1 for details regarding the DEC.) 
• 
If DLTs or Grade ≥3 thrombocytopenia are observed in 2 of the first 3 dosed participants, 
Part 1B will be paused and safety data and PK data will be reviewed by the DEC. The 
dosing strategy for subsequent participants will be determined by the DEC.  
• 
If 8 participants have been enrolled and if DLTs are observed in 3 or more of 8 DLT-
evaluable participants, the dose level will not be cleared and the decision about the next 
dose level will be made by the DEC (i.e., to proceed to Cohort C with niraparib dose 
level -1 [DL-1]). 
If Cohort A is deemed safe based on the mTPI-2 parameters, results of the niraparib PK 
assessment will be taken into consideration when determining the RP2D. If the PK exposure 
for the niraparib TfOS is consistent with the exposure observed in adults, the niraparib dose in 
Cohort A will be the basis of determining the RP2D for the TfOS.  
If the PK exposure for dostarlimab in Cohort A is consistent with the exposures observed in 
adults, then the dose level of niraparib and of dostarlimab from Cohort A will be determined to 
be the RP2D.  
If the PK exposures observed in Cohort A with the niraparib TfOS are substantially lower than 
those observed in adults, a dose escalation cohort (Cohort B) will be opened.  
Cohort B 
The dose of niraparib for Cohort B will be determined based on the PK evaluation in Cohort A, 
and the dose level of dostarlimab will remain the same as in Cohort A.  

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 17 of 213 
If Cohort B is deemed safe based on the mTPI-2 parameters, results of the niraparib PK 
assessment in Cohort B will be taken into consideration when determining the RP2D for TfOS.  
If the PK exposure for the niraparib TfOS in Cohort B is consistent with the exposures 
observed in adults, the niraparib dose in Cohort B will be the basis of determining the RP2D 
for the TfOS.  
Cohort C 
If Cohort A is not cleared based on the mTPI-2 parameters described above, Cohort C will be 
opened using a reduced niraparib dose, determined based on the niraparib PK evaluation in 
Cohort A. The dose of dostarlimab will be the same as in Cohort A.  
If Cohort C is deemed safe based on the mTPI-2 parameters described above, results of the 
niraparib PK assessment in Cohort C will be taken into consideration when determining the 
RP2D for TfOS.  
If the PK exposure for niraparib TfOS in Cohort C is consistent with the exposures observed in 
adults, the niraparib dose level in Cohort C will be the basis of determining the RP2D for 
niraparib TfOS. 
Cohort D 
If the exposures of dostarlimab observed in Cohorts A and B (or Cohorts A and C) are 
substantially lower than those observed in adults, a dose escalation cohort (Cohort D) will be 
opened. The dose of dostarlimab for Cohort D will be determined based on the dostarlimab PK 
evaluation in Cohorts A and B (or Cohorts A and C). A 
 
 may be tested. The dose level of niraparib in Cohort D will be the 
niraparib RP2D as determined from evaluation in Cohorts A, B, and/or C.  
If Cohort D is deemed safe based on the mTPI-2 parameters described above, the dose level of 
dostarlimab from Cohort D will be the RP2D in combination with the niraparib RP2D. If 
Cohort D is not cleared, then the dose level of dostarlimab from Cohort A 
 
 will be the RP2D in combination with the niraparib RP2D.  
If Cohort C is not deemed safe, the study will not continue as designed. 
Alternate niraparib schedules may be implemented for niraparib, if appropriate. 
Additional dose levels of niraparib and/or dostarlimab may be evaluated based on safety and 
PK data from the specific cohorts. Any niraparib dose level other than DL1, DL2, or DL -1 
must first be evaluated in combination with dostarlimab DL1 
 
 prior to evaluating with dostarlimab at DL2 or higher. 
Once the RP2D for the combination of the 
 is determined in 
Part 1B of the study, participants <8 years of age will be eligible for enrolment into the Part 2 
disease-specific expansion cohorts (described in cohort-specific supplements to this protocol).  
In addition, once the RP2D is determined, the RP2D cohort in Part 1B will remain open until 
completion of Part 2 overall for additional enrolment to reach a minimum of N=3 participants 
enrolled in Part 1B RP2D within each age category: ≥6 months to <2 years; ≥2 year to <6 
years; and ≥6 years to <8 years. 
CCI
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 18 of 213 
Dose Limiting Toxicity 
The DLT observation period is 42 days following the initiation of study treatments (i.e., 
approximately the first 2 treatment cycles). A participant will be considered unevaluable for 
DLT assessment if, for reasons other than DLT, the participant does not complete the DLT 
observation period or receives <80% of the intended niraparib dose (e.g., missed 9 or more 
doses; reason for missed doses may include, but is not limited to, noncompliance) or <2 
infusions of dostarlimab. Participants considered unevaluable may be replaced after 
consultation between the Sponsor and Investigator. A participant may continue on study 
treatment following a DLT if the Investigator determines doing so is in the best interest of the 
participant, after discussion by the Investigator with the GSK Medical Monitor, and after 
appropriate recovery from the DLT by the participant. 
DLT is defined as any of the following occurring during the first 42 days of study treatment: 
• 
any treatment-related Grade 4 nonhaematologic clinical (nonlaboratory) AE 
• 
any treatment-related Grade 3 nonhaematologic clinical (nonlaboratory) AE not 
resolving to Grade ≤1 within 48 hours of initiating optimal medical intervention 
• 
any treatment-related Grade 3 or 4 nonhaematologic laboratory abnormality if any of 
the following also occur:  
− 
the abnormality leads to hospitalisation 
− 
the abnormality persists for ≥7 days from the time of AE onset and participant is 
symptomatic from the AE and/or requires intervention 
• 
any treatment-related haematologic toxicity defined as any of the following:  
− 
Grade 4 thrombocytopenia persists for ≥7 days from the time of AE onset or Grade 
3 or 4 thrombocytopenia associated with clinically significant bleeding or 
requiring platelet transfusion 
− 
Grade 4 neutropenia persists for ≥7 days, Grade 3 or 4 neutropenia associated with 
infection, or Grade 3 or 4 febrile neutropenia persists for ≥72 hours 
− 
Grade 4 anaemia or Grade 3 anaemia requiring blood transfusion 
• 
any treatment-related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 
2 
• 
any treatment-related toxicity resulting in the participant receiving <80% of the 
intended niraparib dose and/or <2 dostarlimab infusions due to dose 
modification/interruption/reduction 
• 
any treatment-related Grade ≥2 uveitis, eye pain, or blurred vision that does not resolve 
with topical therapy within 2 weeks 
• 
any treatment-related Grade ≥2 immune-related endocrine toxicity that requires 
hormone replacement, except Grade 2 thyroiditis or thyroid dysfunction 
• 
any treatment-related Grade 2 colitis or diarrhoea that persists for ≥7 days without 
resolution to Grade ≤1 despite adequate steroid therapy 
• 
any Grade 3 or 4 immune-related AE that does not resolve to Grade ≤1 or baseline 
within 8 days despite adequate immune suppressive therapy 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 19 of 213 
• 
Grade 3 or higher infusion-related reaction 
• 
any grade of hemophagocytic lymphohistiocytosis 
• 
any grade of Posterior Reversible Encephalopathy Syndrome (PRES) 
• 
any treatment-related Grade 5 AE 
Safety monitoring in Part 2 is described in the cohort-specific supplements. 
General Study Conduct 
This study consists of a Screening Period (Day -28 to Day -1), a Treatment Period, an End of 
Treatment (EOT) Visit, a Safety Follow-up Visit, and a Follow-up Assessment Period. During 
the Treatment Period, study treatment administration will occur in 3-week cycles. Participants 
will receive niraparib daily or on an alternative schedule in combination with dostarlimab 
Q3W until progressive disease (PD), unacceptable toxicity, withdrawal of consent, 
Investigator’s decision, or death. 
Participants must have a baseline tumour assessment (computed tomography [CT] or magnetic 
resonance imaging [MRI]) of the chest, abdomen, pelvis, and any additional sites as clinically 
indicated within 28 days prior to the first dose of study treatment. Participants with 
neuroblastoma must also have a baseline tumour assessment via metaiodobenzylguanidine-
single-photon emission computed tomography/computed tomography (MIBG-SPECT/CT) or 
fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-positron 
emission tomography [PET]/CT) within 42 days prior to the first dose of study treatment. A 
baseline brain scan (IV contrast-enhanced MRI [preferred] or IV contrast-enhanced CT) is 
required for participants with previously treated brain metastases. (Participants with previously 
treated brain metastases may participate under the conditions detailed in exclusion criterion 5 
in this master protocol and in the exclusion criteria of each cohort-specific supplement for Part 
2.) 
Tumour assessments by CT or MRI of sites involved by disease at baseline and of any 
additional sites as clinically indicated will be done postbaseline, as will MIBG-SPECT/CT or 
FDG-PET/CT tumour assessments (participants with neuroblastoma only). Tumour 
assessments should be conducted every 9 weeks (every 63 [±7] days) following the start of 
study treatment for the first 12 months and then every 12 weeks (every 84 [±7] days) 
thereafter, or more frequently if clinically indicated, until documented PD, the start of 
alternative anticancer treatment, or discontinuation of participant from overall study 
participation (e.g., death, participant’s request, loss to follow-up), whichever comes first. 
Tumour assessments should be scheduled using the date of the first dose of study treatment as 
the reference date for all time points and are not to be scheduled based on the date of the 
previous imaging time point. Imaging assessment delay to conform to study treatment delay is 
not permitted. 
Bone scan, whole body MRI, or PET scan will be carried out at baseline for all participants in 
Part 1 (excluding participants with neuroblastoma) and in the Part 2 Osteosarcoma Expansion 
Cohort within 84 days prior to the first dose of study treatment in order to detect bony sites of 
disease. Subsequent assessments are to be performed during the Treatment Period when 
clinically indicated. If the baseline bone scan, whole body MRI, or PET scan is positive for 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 20 of 213 
metastatic bone disease, a repeat assessment is required for confirmation of partial response 
(PR) or complete response (CR) or if clinically indicated. 
The same imaging technique/modality must be used to follow identified lesions throughout the 
study for a given participant.  
Clinical assessment of superficial lesions should be carried out on the same date as the imaging 
studies or no later than 3 days thereafter and must be recorded in the participant’s electronic 
case report form (eCRF). 
Participants with neuroblastoma will undergo bone marrow assessments at Screening and, if 
positive at baseline, every 9 weeks (every 63 [±7] days) following the start of study treatment 
for the first 12 months and then every 12 weeks (every 84 [±7] days) thereafter, or more 
frequently if clinically indicated, until documented PD, the start of alternative anticancer 
treatment, or discontinuation of participant from overall study participation (e.g., death, 
participant’s request, loss to follow-up), whichever comes first. 
Participants who have a PR or CR while on treatment and who discontinue treatment prior to 
the next disease assessment must have all appropriate follow-up disease assessments to 
confirm the observed response no sooner than 4 weeks (28 days) after the first observation. 
Blood samples to assess niraparib PK, dostarlimab PK, and dostarlimab antidrug antibodies 
(ADAs) and neutralising antibodies (NAb) will be collected from all participants pre- and 
postdose at the time points specified in Table 3. 
 
 
 Blood samples should be collected in order of priority as 
outlined in Section 8.2. Tumour samples will be collected from all participants in Part 2 and 
also from Part 1 participants, but only under specific circumstances such as a treatment 
response. 
Safety assessments conducted throughout the Treatment Period include symptom-directed 
physical examinations, electrocardiograms (ECGs), vital signs, and clinical laboratory 
assessments, including complete blood count (CBC) with differential, coagulation profile, 
chemistry, thyroid function panel, and pregnancy testing (irrespective of prior medical 
treatment). Psychological assessments will be administered as per local standard of care. 
 
 
 
 
All participants will undergo an EOT Visit conducted within 7 days of the decision to 
discontinue study treatment and a Safety Follow-up Visit 30 (+7) days after the last date of 
study treatment administration. Participants are expected to complete the Safety Follow-up 
Visit regardless of reason for study treatment discontinuation and even if they have started 
alternative anticancer therapy. During the long-term Follow-up Assessment Period, 
participants will be followed via clinic visit or telephone contact (if an in-person visit is not 
possible) every 90 (±14) days after last dose of study treatment for the first year, every 180 
(±14) days for the subsequent 2 years, and yearly (±14 days) for an additional 2 years (5 years 
total), or until the start of alternative anticancer therapy (unless there is an ongoing AE/serious 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 21 of 213 
AE [SAE] that must be followed until resolved, stabilised, or otherwise explained), or until the 
participant withdraws from the study overall, is lost to follow-up, or dies (whichever occurs 
earlier). 
Collection and recording of all AEs for each participant will start on the day of informed 
consent/assent. Nonserious AEs will be collected until 30 days after the last dose of study 
treatment. SAEs will be collected until 90 days after the last dose of study treatment (or to a 
minimum of 30 days after the last dose of study treatment if the participant starts alternative 
anticancer treatment). However, any SAEs assessed as related to study participation or related 
to study treatment will be collected through the Follow-up Assessment Period. Adverse events 
of special interest (AESIs) are defined in Appendix 2; AESIs will be collected through the 
Follow-up Assessment Period as described in Section 8.3.6. Details of all pregnancies in 
female participants and, if indicated, female partners of male participants who receive study 
treatment will be collected until 180 days after the last dose of study treatment in female 
participants and 90 days after the last dose of study treatment for female partners of male 
participants. In addition, all ongoing AEs and SAEs are to be followed, regardless of start of 
alternative anticancer therapy, until the event is resolved, stabilised, or otherwise explained or 
until the participant has withdrawn consent to the study overall, is lost to follow-up (as defined 
in Section 7.4), or has died.  
Number of Participants (actual and planned): Under Protocol Amendment 03, 
approximately 56 participants were planned to be enrolled in Part 1 of the study, including 
approximately 32 participants in Part 1A and approximately 24 participants in Part 1B (unless 
the incidence of DLTs dictated fewer participants as per the Dose Escalation Plan described in 
Section 4.1). 
A total of 23 participants were enrolled into Part 1A Cohorts 0, 1A, and 1B. Part 1A Cohort 1B 
was not deemed to be safe, and, as a result, no participants were enrolled into Part 1A Cohort 
2. In addition, a total of 3 participants were enrolled into Part 1B Cohort 1, for which 
enrolment into Part 1B Cohort 1 was prematurely stopped due to DLTs of Grade ≥3 
thrombocytopenia.  
Under Protocol Amendment 05, it is anticipated that 1 to 3 cohorts (8 participants per cohort or 
approximately 24 participants overall) may be enrolled in Part 1B, unless the incidence of 
DLTs dictates fewer participants as noted above for Part 1A and in Section 4.1. Additional 
cohorts (including up to 8 participants per cohort) may be opened in Part 1B if needed to 
evaluate alternative niraparib dose levels. Lastly, up to 5 additional participants may be 
enrolled into Part 1B to further evaluate the youngest participant group(s) if not represented.  
Numbers of participants for the Part 2 Osteosarcoma and Neuroblastoma Expansion Cohorts 
are discussed in the relevant protocol supplement. 
Diagnosis and Main Criteria for Inclusion: 
Participant will be eligible for Part 1 of the study if all of the following criteria are met: 
1. 
 
 
 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 22 of 213 
2. Participant is child or adolescent ≥6 months to <18 years old at the time of informed 
consent/assent. If a participant is enrolled under Protocol Amendment 05, the participant 
must be ≥6 months to <8 years old at the time of informed consent/assent. 
3. Participant with disease other than neuroblastoma has radiologically measurable disease at 
screening that can be tracked as RECIST v1.1 target lesion(s). 
Participant with neuroblastoma has measurable/evaluable target and/or non-target disease 
by INRC at screening. Neuroblastoma participants with recurrent/relapsed bone metastasis 
that is metaiodobenzylguanidine (MIBG)-positive (or FDG-positive, for MIBG-nonavid 
tumours) as only site of disease are eligible. 
4. Under Protocol Amendment 03 (or earlier), a participant in Part 1A must be able to swallow 
the 
 and have a baseline body weight of ≥20 kg. Participants in Part 
1A who are unable to swallow the 
 or who have a baseline body 
weight <20 kg are eligible to receive the niraparib 
 only. As of Protocol 
Amendment 04, there are no inclusion criteria addressing ability to swallow niraparib 
tablets. 
5. Performance status must be ≥60% on the Karnofsky scale for participants >16 years of age 
and ≥60% on the Lansky scale for participants ≤16 years of age. 
Note: Neurologic deficits in participants with brain metastases must have been stable for at 
least 7 days prior to study enrolment. Participants who are unable to walk because of 
paralysis, but who are upright in a wheelchair, will be considered ambulatory for the 
purpose of assessing the performance status. 
6. Participant has adequate organ function, defined as follows:  
Note: The participant must not have received blood transfusion, growth factors, or platelet 
stimulating agents in the 14 days prior to providing a sample for haematologic analysis 
nor erythropoietin in the prior 6 weeks. 
a. absolute neutrophil count (ANC) ≥1000/μL 
b. platelets ≥100 000/μL 
c. haemoglobin ≥8 g/dL or ≥5.0 mmol/L 
CCI
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 23 of 213 
d. serum creatinine≤1.5×upper limit of normal (ULN) for age or calculated creatinine 
clearance or radioisotope glomerular filtration rate ≥60 mL/min/1.73m2 
e. total bilirubin ≤1.5 × ULN or direct bilirubin ≤1 × ULN 
f. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN 
unless liver metastases are present, in which case AST and ALT must be ≤5 × ULN 
g. international normalised ratio or prothrombin time (PT) ≤1.5 × ULN unless the 
participant is receiving anticoagulant therapy, as long as PT or partial thromboplastin 
time (PTT) is within therapeutic range of intended use of anticoagulants 
h. activated PTT ≤1.5 × ULN unless the participant is receiving anticoagulant therapy as 
long as PT or PTT is within therapeutic range of intended use of anticoagulants 
7. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at 
least one of the following conditions applies:  
a. Is not a woman of childbearing potential (WOCBP). 
Or 
b. 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 3, from the Screening Visit through at least 180 days after the last dose of 
study treatment and agrees not to donate eggs (ova, oocytes) for the purpose of 
reproduction during this period. The Investigator should evaluate the effectiveness of 
the contraceptive method in relationship to the first dose of study treatment. 
c. A WOCBP must have a negative highly sensitive pregnancy test (urine or serum, as 
required by local regulations) within 24 hours prior to the first dose of study treatment 
and irrespective of prior medical treatment. 
Additional requirements for pregnancy testing during and after the Treatment Period are 
located in Section 8.2.9. 
The Investigator is responsible for review of medical history, menstrual history, and 
recent sexual activity to decrease the risk for inclusion of a woman with an early 
undetected pregnancy. 
8. A male participant of reproductive potential is eligible to participate if he agrees to the 
following starting with the first dose of study treatment through at least 90 days (a 
spermatogenesis cycle) after the last dose of study treatment: 
a. refrain from donating sperm 
plus, either: 
b. be abstinent from heterosexual intercourse as their preferred and usual lifestyle 
(abstinent on a long-term and persistent basis) and agree to remain abstinent  
or 
c. must agree to use a male condom and should also be advised of the benefit for a 
female partner to use a highly effective method of contraception, as a condom may 
break or leak, when having sexual intercourse with a WOCBP who is not currently 
pregnant. 
9. The Investigator, or a person designated by the Investigator, will obtain written informed 
consent from each study participant or the participant’s legally acceptable representative, 
parent(s), or legal guardian and the participant’s assent, when applicable, before any study-
specific activity is performed. The Investigator will retain the original copy of each 
participant’s signed consent/assent document. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 24 of 213 
Inclusion criteria for Part 2 of the study are described in each cohort-specific supplement. 
Main Criteria for Exclusion: 
Participant will not be eligible for study entry if any of the following criteria are met: 
1. Participation presents unacceptable risk to the prospective participant based on the 
Investigator’s judgment. 
2. Participant has known hypersensitivity to dostarlimab or niraparib, their components, or 
their excipients. 
3. Participant has a known history of myelodysplastic syndrome or acute myeloid leukaemia. 
4. Participant has active autoimmune disease that has required systemic treatment in the past 
2 years (i.e., with use of disease-modifying antirheumatic drugs, corticosteroids, or 
immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic 
corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered 
a form of systemic treatment.  
5. Participant has known active CNS metastases, carcinomatous meningitis, or both. Note: 
Participants with previously treated brain metastases may participate provided they are 
clinically stable and have no evidence of new, enlarging, or progressing brain metastases 
(using the identical imaging modality for each assessment, either MRI or CT scan) for at 
least 4 weeks (28 days) prior to the first dose of study treatment. In addition, the 
participant must not have been using steroids for at least 7 days prior to the first dose of 
study treatment. Carcinomatous meningitis precludes a participant from study participation 
regardless of clinical stability. 
6. Participant had a known additional (second primary) malignancy that progressed or 
required active treatment within the last 2 years. 
7. Participant is considered a poor medical risk due to a serious, uncontrolled medical 
disorder, nonmalignant systemic disease, or active infection that requires systemic therapy. 
Specific examples include, but are not limited to, history of (noninfectious) pneumonitis 
that required steroids or current pneumonitis, uncontrolled ventricular arrhythmia, 
uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava 
syndrome, or any psychiatric or substance abuse disorders that would interfere with 
cooperation with the requirements of the study (including obtaining assent/consent). 
8. Participant has a condition (such as transfusion-dependent anaemia or thrombocytopenia), 
requirement for therapy, or laboratory abnormality that might confound the study results or 
interfere with the participant’s participation for the full duration of the study treatment.  
9. Participant is pregnant, breastfeeding, or expecting to conceive within the projected 
duration of the study, starting with the Screening Visit through 180 days after the last dose 
of study treatment. 
No data are available regarding the presence of dostarlimab or niraparib or its metabolites 
in human milk, or on its effects on the breastfed infant or milk production. Because of the 
potential for serious adverse reactions in breastfed infants from dostarlimab and/or 
niraparib, female participants should not breastfeed during treatment with dostarlimab 
and/or niraparib and for at least 4 months after the last dose of dostarlimab or at least 30 
days after the last dose of niraparib, whichever is longer. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 25 of 213 
10. Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or 
any other form of immunosuppressive therapy within 7 days prior to the first dose of study 
treatment. 
11. Participant has a known history of HIV (type 1 or 2 antibodies). 
12. Participant has documented presence of HbsAg and/or HBcAb at Screening or within 3 
months prior to first dose of study intervention. Participants with a negative HbsAg and 
positive HbcAb result are eligible only if HBV DNA is negative (Appendix 12) 
13. Participant must not have a gastrointestinal condition, such as bowel obstruction, that can 
impact absorption of oral medications and is identified by clinical symptoms or CT scan, 
etc. 
14. Participant has had any known Grade 3 or 4 anaemia, neutropenia, and/or 
thrombocytopenia that was related to the most recent prior anticancer treatment and that 
persisted >4 weeks (28 days). 
15. Participant has not recovered (i.e., to Grade ≤1 or to baseline) from prior systemic 
anticancer therapy-induced AEs. Note: Participants with alopecia, hearing impairment, 
Grade ≤2 neuropathy, Grade ≤2 fatigue, Grade ≤2 anaemia, and/or Grade ≤2 neutropenia 
are an exception to this criterion and may qualify for participation in the study. 
16. Participant had toxicity related to prior immunotherapy that led to treatment 
discontinuation. 
17. Participant had treatment with systemic anticancer therapy (investigational agent or device, 
or approved chemotherapy, targeted therapy, immunotherapy, or other systemic therapy) 
within 3 weeks or 5 half-lives, whichever is shorter, prior to the first dose of study 
treatment; radiation therapy encompassing >20% of the bone marrow within 2 weeks prior 
to the first dose of study treatment; or any radiation therapy within 1 week prior to the first 
dose of study treatment. 
18. Participant has not recovered adequately from AEs or complications from any major 
surgery prior to starting study treatment. 
19. Participant has received a live vaccine within 30 days of planned start of study treatment. 
20. Participant has clinically significant cardiovascular disease (e.g., significant cardiac 
conduction abnormalities, uncontrolled hypertension, cardiac arrhythmia or unstable 
angina, New York Heart Association Grade 2 or greater congestive heart failure, serious 
cardiac arrhythmia requiring medication, and history of cerebrovascular accident) within 6 
months of enrolment. 
21. Participant has heart rate-corrected QT interval prolongation at screening >450 msec or 
>480 msec for participants with bundle branch block. 
Notes: 
• 
The QTc is the QT interval corrected for heart rate according to Bazett’s formula 
(QTcB), Fridericia’s formula (QTcF), and/or another method, machine read or 
manually over read. 
• 
The specific formula that will be used to determine eligibility and discontinuation 
for an individual participant must be determined prior to initiation of the study and 
used consistently for eligibility and study assessments. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 26 of 213 
22. Participant has received a solid organ transplant.  
23. Participant has a documented presence of HCV antibody at Screening or within 3 months 
prior to first dose of study intervention. NOTE: Participants with a positive HCV antibody 
test result due to prior resolved disease can be enrolled, if a confirmatory HCV RNA test is 
negative and the participant otherwise meets entry criteria. 
24. Participant has a documented presence of HCV RNA at Screening or within 3 months prior 
to first dose of study intervention. NOTE: The HCV RNA test is optional and participants 
with negative HCV antibody test are not required to undergo HCV RNA testing as well. 
Exclusion criteria for Part 2 of the study are described in each cohort-specific supplement. 
Investigational Product, Dosage and Mode of Administration: 
 
 
 
 Dostarlimab infusion will be administered before the niraparib 
dose at the study site on Day 1 of each 21-day treatment cycle (Q3W). Dostarlimab will be 
administered through a 30-minute infusion. A window between -5 minutes and +15 minutes is 
permitted, in the absence of any clinically significant infusion-related reaction that would 
necessitate interruption and/or increased infusion interval. 
Duration of Treatment: Study treatment may continue until documented PD, unacceptable 
toxicity, withdrawal of consent, Investigator’s decision, or death. 
Reference Therapy, Dosage, and Mode of Administration: 
Not applicable. 
Criteria for Evaluation: 
Safety 
• 
DLTs during the first 42 days following the initiation of study treatment (i.e., 
approximately the first 2 treatment cycles) in Part 1. 
• 
The incidence of treatment-emergent adverse events (TEAEs) occurring while 
participants are on treatment until 30 days after the last dose of study treatment for AEs, 
until 90 days after the last dose of study treatment for SAEs (or 30 days after last dose 
for SAEs if the participant starts alternative anticancer treatment), and study 
treatment-related SAEs and AESIs will be collected through the Follow-up Assessment 
Period (see Section 8.3.6) until the discontinuation of the participant from overall study 
participation. 
• 
Changes in clinical laboratory parameters (haematology, chemistry, thyroid function), 
urinalysis (if obtained), vital signs, physical examinations, ECGs, and usage of 
concomitant medications. 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 27 of 213 
Efficacy 
• 
ORR, defined as the proportion of participants with a best overall response (BOR) of 
confirmed CR or PR as determined by the Investigator using RECIST v1.1 or INRC 
(for participants with neuroblastoma only).  
• 
DOR, defined as the time from first documentation of confirmed response (CR or PR) 
until the time of first documented PD by RECIST v1.1 or INRC (for participants with 
neuroblastoma only) based on Investigator assessment, or death (whichever occurs 
first). 
Pharmacokinetics 
The PK parameters will be estimated by population PK methods with appropriate adjustment 
for key covariates including age and body weight. 
Antidrug Antibodies 
Dostarlimab ADAs will be analysed in a tiered approach (i.e., screening, confirmation, titre, 
and neutralising antibody assay) using electrochemiluminescence, if appropriate. 
Statistical Methods: 
Sample Size Consideration 
The sample size of approximately 56 participants in total is not based on formal statistical 
hypotheses but is estimated based on an mTPI-2 dose escalation design for Part 1 including 
approximately 7 cohorts (4 cohorts originally planned in Part 1A under Protocol Amendment 
03 and 3 cohorts planned in Part 1B under Protocol Amendments 04 and 05 [8 participants per 
each of the 7 cohorts]). Up to 5 additional participants may be enrolled to further evaluate the 
youngest participant group(s) if not represented. 
Analysis Populations 
• 
The DLT-evaluable Population consists of participants in Part 1 who complete the DLT 
observation period through at least 2 cycles of study treatment (including ≥80% of the 
intended niraparib dose and ≥2 infusions of dostarlimab) or experience a DLT. 
• 
The Safety Population is defined as all participants who receive at least 1 dose of either 
niraparib or dostarlimab. 
• 
The Intent-to-Treat (ITT) Population includes all participants who receive any study 
medication and have measurable baseline tumour assessment and/or, for neuroblastoma 
participants, MIBG-positive disease (or FDG-positive disease, for MIBG-nonavid 
tumours) at baseline. 
• 
The modified ITT (mITT) Population includes all participants who receive any study 
medication, have measurable baseline tumour assessment, and/or, for neuroblastoma 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 28 of 213 
participants, MIBG-positive disease (or FDG-positive disease, for MIBG-nonavid-
tumours) at baseline, and have at least 1 postbaseline tumour assessment.  
• 
The Per protocol Population includes all participants in the mITT Population who do 
not have protocol violations during the study that may significantly impact the 
interpretation of efficacy results. 
• 
The PK Population includes all participants who receive at least one dose of study 
treatment and have at least one PK sample. PK Populations are defined separately for 
each agent. 
• 
Immunogenicity (ADA) Population includes all participants who receive at least 1 dose 
of dostarlimab and who have at least 1 ADA sample with a result. 
General Methods 
All descriptive statistical analyses will be performed using the most recently released and 
available SAS statistical software, unless otherwise noted. For categorical variables, the 
number and percent of each category within a parameter will be calculated. For continuous 
variables, the sample size (n), mean, median, and standard deviation, as well as the minimum 
and maximum values, will be presented.  
 
 
 
 
 
 
 
Details of the statistical analyses presented below will be provided in the study’s statistical 
analysis plan. 
Efficacy Analysis 
The number and proportion of participants with an objective response will be tabulated by dose 
cohort and overall. ORR will be calculated along with its estimated 2-sided 95% CI. Among 
the participants with a confirmed response, a time-to-event analysis of DOR will be performed 
using Kaplan-Meier method, including quartile estimates and two-sided 95% CI.  
Safety Analysis 
For Part 1, the incidence of DLTs will be summarised by study part and cohort for the DLT-
evaluable Population. For all parts of the study, additional safety data will be summarised for 
the Safety Population. 
AEs will be classified using the Medical Dictionary for Regulatory Activities (MedDRA) 
v20.0 or later. All AEs occurring during the study will be included in by-participant data 
listings and tabulated by MedDRA system organ class and preferred term. Safety parameters 
will include the incidence of TEAEs, related TEAEs, serious TEAEs, TEAEs of Grade 3 or 
greater by National Cancer Institute Common Terminology Criteria for Adverse Events v5, 
TEAEs leading to death, TEAEs leading to treatment discontinuation, and TEAEs leading to 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 29 of 213 
dose modification. AESIs will also be summarised and listed. No formal hypothesis-testing 
analysis of AE incidence rates will be performed. 
All AEs occurring on study will be listed in participant data listings. By-participant listings 
also will be provided for the following: participant deaths, SAEs, and AEs leading to 
withdrawal of study treatment. 
Clinical laboratory tests, vital signs, ECG results, physical examination findings, performance 
status, and concomitant medication usage will be listed per participant for each assessment, 
and descriptive statistics will be tabulated for selected safety parameters. 
PK and Immunogenicity Analysis 
The PK characteristics of niraparib and dostarlimab will be evaluated in the PK Population 
using sparse blood sampling and population PK analysis approaches. Serum concentrations of 
dostarlimab and 
 will be presented 
using descriptive statistics by dose cohort and overall. Summary statistics will include mean, 
standard deviation, coefficient of variation (CV), geometric mean, geometric mean CV, 
median, and minimum and maximum values. The 
 concentration data 
may be used to evaluate the age-related metabolism development of niraparib in paediatric 
participants, if data permit. Niraparib and dostarlimab concentration‑time data will be analysed 
using a population approach. A nonlinear mixed effects model will be used to determine 
population PK parameters and identify relevant covariates (e.g., age, weight, or disease‑related 
covariates). The data from this study may be combined with data from other studies and the 
results of these analyses will be described in a separate report. 
Serum samples for the determination of anti-dostarlimab antibodies will be aliquots of the 
same samples collected as for PK. Minimally, ADA will be analysed using 
electrochemiluminescence with samples collected prior to all dostarlimab doses as indicated in 
the Schedule of Activities, as well as at EOT, at the Safety Follow-up Visit (30-days post-
treatment), and at the first Follow-up Visit (90-days post-treatment). The summary of number 
and percent of participants who become positive for ADAs and who develop NAb will be 
based on dose regimen, part, visit/time, and overall.  
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 30 of 213 
1.2. 
Schemas 
 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 31 of 213 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 32 of 213 
1.3. 
Schedule of Activities (SoA) 
The Schedule of Activities (SoA) for Part 1, inclusive of cohort-specific activities is 
provided in Table 3. The tumour assessment flowchart is presented in Table 4. The SoAs 
specific to the cohorts will be provided in the supplements.  
The study will be conducted in conformance with the protocol, Good Clinical Practice 
(GCP), and applicable regulatory requirements. Regulatory, ethical, and study oversight 
considerations are provided in Appendix 1. 
 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 33 of 213 
Table 3: 
Schedule of Activities 
Protocol Activity 
Screening 
Period 
Treatment Period 
EOT 
Visita,b 
Safety FUP 
Visit 
(30 [+7] Days 
Post-
Treatment)b 
FUP 
Assessment 
Period 
(Every 90 [±14] 
Days Post-
Treatment)c 
Study treatment cycle 
 
Cycles 1-2 
Cycles 3+ 
 
 
 
Cycle week 
 
1 
2 
3 
1 
2 
 
 
 
Study day 
-28 to -1 
 
 
 
 
 
 
 
 
Study visit window (days 
within cycle) 
 
±3 
±3 
±3 
±3 
±3 
+7 
+7 
±14 
Procedure 
 
 
 
 
 
 
 
 
 
Informed consent/assentd 
X 
 
 
 
 
 
 
 
 
Demographics and 
medical history 
X 
 
 
 
 
 
 
 
 
Performance status 
X 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
X 
 
 
 
 
 
 
 
 
Physical examination 
X 
A complete physical examination is to be conducted at Screening and EOT only, and as clinically 
indicated. 
 
 
Psychological 
assessmentsf 
X 
 
 
 
 
 
X 
 
 
Vital signs, weight, and 
heightg 
X 
X 
X 
X 
X 
X (Cycle 3 only) 
X 
X 
X 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 34 of 213 
Protocol Activity 
Screening 
Period 
Treatment Period 
EOT 
Visita,b 
Safety FUP 
Visit 
(30 [+7] Days 
Post-
Treatment)b 
FUP 
Assessment 
Period 
(Every 90 [±14] 
Days Post-
Treatment)c 
Study treatment cycle 
 
Cycles 1-2 
Cycles 3+ 
 
 
 
Cycle week 
 
1 
2 
3 
1 
2 
 
 
 
Study day 
-28 to -1 
 
 
 
 
 
 
 
 
Study visit window (days 
within cycle) 
 
±3 
±3 
±3 
±3 
±3 
+7 
+7 
±14 
Procedure 
 
 
 
 
 
 
 
 
 
CBC with differentialh 
X 
Twice 
weekly 
Twice 
weekly 
Twice 
weekly 
X 
 
X 
 
 
Coagulationh 
X 
As clinically indicated 
X 
 
 
Blood chemistryh 
X 
X 
X 
X 
X 
 
X 
 
 
Serum or urine pregnancy 
test (WOCBP only)i 
X 
X 
 
 
X 
 
X 
X 
X 
12-lead ECGk 
X 
 
 
 
X 
(Cycle 3 
only) 
 
X 
 
 
Dostarlimab 
administration 
 
X 
 
 
X 
 
 
 
 
Niraparib 
dispensed/collected 
(administered Day 1 after 
dostarlimab infusion) 
 
X 
 
 
X 
 
X 
(Collect-
ion only) 
 
 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 35 of 213 
Protocol Activity 
Screening 
Period 
Treatment Period 
EOT 
Visita,b 
Safety FUP 
Visit 
(30 [+7] Days 
Post-
Treatment)b 
FUP 
Assessment 
Period 
(Every 90 [±14] 
Days Post-
Treatment)c 
Study treatment cycle 
 
Cycles 1-2 
Cycles 3+ 
 
 
 
Cycle week 
 
1 
2 
3 
1 
2 
 
 
 
Study day 
-28 to -1 
 
 
 
 
 
 
 
 
Study visit window (days 
within cycle) 
 
±3 
±3 
±3 
±3 
±3 
+7 
+7 
±14 
Procedure 
 
 
 
 
 
 
 
 
 
Tumour assessment: 
CT or MRI l – 
All participants m 
Xn,o 
Every 9 weeks (every 63 [±7] days) following the start of study treatment for the first 
12 months and then every 12 weeks (every 84 [±7] days) thereafter, or more 
frequently if clinically indicated, until documented PD, the start of alternative 
anticancer treatment, or discontinuation from overall study participation (e.g., death, 
participant’s request, or participant is lost to follow-up), whichever comes firstp 
Xq 
Tumour assessment: 
MIBG-SPECT/CT or 
FDG-PET/CT – 
Participants with 
neuroblastoma only m 
Xn,o 
Every 9 weeks (every 63 [±7] days) following the start of study treatment for the first 12 
months and then every 12 weeks (every 84 [±7] days) thereafter, or more frequently if 
clinically indicated, until documented PD, the start of alternative anticancer treatment, or 
discontinuation from overall study participation (e.g., death, participant’s request, or 
participant is lost to follow-up), whichever comes firstp 
Note: MIBG-SPECT/CT should be used for participants with MIBG-avid tumours and 
FDG-PET/CT should be used as an alternative modality for participants whose 
tumours do not concentrate MIBG. 
Xq 
Tumour assessment: Bone 
scan, whole body MRI, or 
PET scan – Part 1 
(excluding participants 
with neuroblastoma) and 
Osteosarcoma Expansion 
Cohort m, r 
Xo 
Required throughout this interval if clinically indicated and to confirm disease response if baseline scan was positive for metastatic bone 
disease 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 36 of 213 
Protocol Activity 
Screening 
Period 
Treatment Period 
EOT 
Visita,b 
Safety FUP 
Visit 
(30 [+7] Days 
Post-
Treatment)b 
FUP 
Assessment 
Period 
(Every 90 [±14] 
Days Post-
Treatment)c 
Study treatment cycle 
 
Cycles 1-2 
Cycles 3+ 
 
 
 
Cycle week 
 
1 
2 
3 
1 
2 
 
 
 
Study day 
-28 to -1 
 
 
 
 
 
 
 
 
Study visit window (days 
within cycle) 
 
±3 
±3 
±3 
±3 
±3 
+7 
+7 
±14 
Procedure 
 
 
 
 
 
 
 
 
 
Bone marrow assessment 
– Participants with 
neuroblastoma only 
Xs 
If positive at baseline, every 9 weeks (every 63 [±7] days) following the start of study 
treatment for the first 12 months and then every 12 weeks (every 84 [±7] days) 
thereafter, or more frequently if clinically indicated, until documented PD, the start of 
alternative anticancer treatment, or discontinuation from overall study participation 
(e.g., death, participant’s request, or participant is lost to follow-up), whichever comes 
first.  Required for all participants to confirm disease response. 
Xq 
AE monitoring u 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Prior and concomitant 
medications and nondrug 
treatments 
X 
Medications and nondrug treatments will be monitored for study purposes from Screening to at least 30 days 
following the last dose of study treatment 
 
Blood sample for 
dostarlimab PK and/or 
ADAs and neutralising 
antibodies v, w 
 
X 
X (Cycle 1 
only) 
 
X (predose, 
Cycles 4 and 
6, and every 
6 cycles 
thereafter) 
 
X 
X 
X 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 37 of 213 
Protocol Activity 
Screening 
Period 
Treatment Period 
EOT 
Visita,b 
Safety FUP 
Visit 
(30 [+7] Days 
Post-
Treatment)b 
FUP 
Assessment 
Period 
(Every 90 [±14] 
Days Post-
Treatment)c 
Study treatment cycle 
 
Cycles 1-2 
Cycles 3+ 
 
 
 
Cycle week 
 
1 
2 
3 
1 
2 
 
 
 
Study day 
-28 to -1 
 
 
 
 
 
 
 
 
Study visit window (days 
within cycle) 
 
±3 
±3 
±3 
±3 
±3 
+7 
+7 
±14 
Procedure 
 
 
 
 
 
 
 
 
 
Blood sample for 
niraparib PK w, x 
 
X (Cycle 1 
and 2)  
X (Cycle 1 
only) 
 
 
 
 
 
 
Alternative anticancer 
treatment assessment 
 
 
 
 
 
X 
X 
X 
X 
Abbreviations: ADA=antidrug antibody; AE=adverse event; AESI=adverse event of special interest; ALP=alkaline phosphatase; BP=blood pressure; 
 
 CBC=complete blood count; CNS=central nervous system; CR=complete response; CT=computed tomography; ECG=electrocardiogram; eCRF=electronic case report 
form; EOT=End of Treatment; FDG-PET/CT=fluorodeoxyglucose-positron emission tomography/computed tomography; FUP=follow-up; G-CSF=granulocyte-colony stimulating 
factor; HbcAb=hepatitis B core antibody; HbsAg=hepatitis B surface antigen; HCVAb=Hepatitis C virus antibody; INRC=International Neuroblastoma Response Criteria; 
IV=intravenous; MIBG-SPECT/CT=metaiodobenzylguanidine-single-photon emission computed tomography/computed tomography; MRI=magnetic resonance imaging; 
PD=progressive disease; PET=positron emission tomography; PK=pharmacokinetics; PR=partial response; RECIST=Response Evaluation Criteria in Solid Tumours; 
SAE=serious adverse event; WOCBP=woman of childbearing potential. 
a. 
All participants will undergo an EOT Visit no more than 7 days following the decision to discontinue study treatment for any reason. 
b. 
The Safety FUP Visit and EOT Visit can be combined if both fall within the same window. The Safety FUP Visit is to take place no sooner than 30 days after last dose to permit the 
protocol-required collection of AEs/SAEs occurring during this 30-day interval. The Safety FUP Visit has a window of +7 days. 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 38 of 213 
c. 
During the FUP assessment period, participants will be followed via clinic visit or telephone contact every 90 (±14) days after the last dose of study treatment for the first year, 
every 180 (±14) days for the subsequent 2 years, and yearly (±14 days) for an additional 2 years (5 years total); or until the start of alternative anticancer therapy (unless there is 
an ongoing AE/SAE that must be followed until resolved, stabilised, or otherwise explained), the participant withdraws from the study overall, is lost to follow-up, or dies (whichever 
occurs earlier). 
d. 
Informed consent/assent must be obtained prior to undergoing any study-specific procedure and may occur prior to the 28-day Screening Period. 
f. 
Psychological assessments to be performed as per local standard of care. 
g. 
Vital signs include temperature, blood pressure, heart rate, and respiratory rate. All vital signs will be taken before, every 15 to 30 minutes during, and at the end of every 
dostarlimab infusion. Throughout the Treatment Period, all vital signs will be monitored at Week 1 of each cycle even if dostarlimab is not administered. In addition, for the first 8 
weeks of the Treatment Period (up to and including Cycle 3 Week 2), all vital signs will be monitored at Week 2 and Week 3 of each cycle. Height and weight will be measured at 
screening, Day 1 of each cycle, EOT, 30-Day Safety Follow-up, and during the FUP Assessment Period. 
h. 
Haematology, coagulation, and chemistry assessments will be performed by local laboratories. Parameters required in this study are listed in Table 15. Haematology, coagulation, 
and chemistry assessments must be measured within 7 days prior to Cycle 1 Day 1 to confirm eligibility. Haematology and chemistry must be performed and results evaluated 
prior to study treatment administration. Haematology is to be checked twice each week during the first 2 cycles of study treatment for all participants. Haematology tests may be 
performed at a laboratory facility other than the study site, but the test results must be reported to the study site, the study site must keep a copy of test results with the 
participant’s study file, and the results must be entered into the eCRF. If dose interruption or modification is required at any point on study because of haematologic toxicity, 
weekly blood draws for CBC will be done according to Table 10. Additional haematology or chemistry assessments may be performed according to local standard of care or as 
clinically indicated. If Cycle 1 Day 1 is no more than 7 days after sample collection for Screening, these samples do not need to be collected again for Cycle 1 Day 1, unless 
clinically warranted. Additional monitoring for haematology is to be performed after a niraparib dose increase due to a birthday or due to a weight increase that moves participants 
to a higher 
, respectively. Haematology is to be checked twice each week during the first 2 cycles of study treatment after the niraparib dose 
increase. Blood samples should be collected in order of priority as outlined in Section 8.2.  
i. 
If the participant is a WOCBP, urine or serum pregnancy test will be performed by the local laboratory at the Screening Visit, within 24 hours prior to the first dose of study 
treatment, on Day 1 of every cycle for the duration of the Treatment Period, at the EOT Visit, at the 30-Day Safety Follow-up Visit, and 180 (±14) days after the last dose of study 
treatment. Pregnancy testing should occur irrespective of prior medical treatment. The results from these tests must be available and negative before study treatment is 
administered. Additional pregnancy testing may be necessary if required by local practices or regulations or if potential pregnancy is suspected. 
k. 
ECG should be repeated at Cycle 3 Week 1 and EOT, as well as during the Treatment or FUP Periods if clinically indicated. 
l. 
CT scans should be performed with contrast agents unless contraindicated for medical reasons. MRI of the abdomen and pelvis can be substituted for CT if MRI adequately 
depicts the disease. However, MRI of the chest should not be substituted for CT of chest even if IV contrast is contraindicated. In such a case, CT will be performed without 
contrast to evaluate the lung parenchyma. If MRI is used to follow -up bone lesion(s), it must be performed prior to any treatment that may affect bone marrow cellularity (e.g., G-
CSF). PET/CT may be used according to RECIST v1.1 or INRC (participants with neuroblastoma only) guidelines with full-dose diagnostic CT and as clinically indicated. 
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 39 of 213 
m. The same imaging technique/modality must be used to follow identified lesions throughout the study for a given participant. Clinical assessment of superficial lesions should be 
carried out on the same date as the imaging studies or no later than 3 days thereafter and must be recorded in the participant’s eCRF. 
n. 
Participants must have a baseline tumour assessment (CT or MRI) of the chest, abdomen, pelvis, and any additional sites as clinically indicated within 28 days prior to the first 
dose of study treatment. Participants with neuroblastoma must also have a baseline tumour assessment via MIBG-SPECT/CT or FDG-PET/CT within 42 days prior to the first 
dose of study treatment. A baseline brain scan (IV contrast-enhanced MRI [preferred] or IV contrast-enhanced CT scan) is required for participants with previously treated brain 
metastases. (Participants with previously treated brain metastases may participate under the conditions detailed in Exclusion Criterion 5 in this master protocol and in each cohort-
specific supplement for Part 2.) 
o. 
Radiologic assessments obtained per the standard of care prior to enrolment into the study do not need to be repeated and are acceptable to use as baseline evaluations, if all of 
the following conditions are met:  
• 
the CT or MRI tumour assessments were obtained within 28 days prior to the first dose of study treatment/the MIBG-SPECT/CT or FDG-PET/CT tumour assessments 
were obtained within 42 days prior to the first dose of study treatment (participants with neuroblastoma only)/the bone scan, whole body MRI, or PET tumour 
assessments were obtained within 84 days prior to the first dose of study treatment (Part 1 [excluding participants with neuroblastoma] and the Osteosarcoma 
Expansion Cohort),  
• 
the assessments were performed using the method requirements outlined in RECIST v1.1 or INRC (participants with neuroblastoma only),  
• 
the same imaging technique/modality must be used to follow identified lesions throughout the study for a given participant, and  
• 
appropriate documentation indicating that these radiologic tumour assessments were performed as standard of care is available in the participant’s source notes. 
p. 
Tumour assessments by CT or MRI of sites involved by disease at baseline and of any additional sites as clinically indicated will be done postbaseline, as will MIBG-SPECT/CT or 
FDG-PET/CT tumour assessments (participants with neuroblastoma only) (see Table 4). Tumour assessments, including bone marrow assessments, will be conducted on the 
schedule shown in Table 3. Tumour assessments should be scheduled using the date of the first dose of study treatment as the reference date for all time points and are not to be 
scheduled based on the date of the previous imaging time point. Imaging assessment delay to conform to study treatment delay is not permitted.  
q. 
Participants who have already demonstrated documented PD as per RECIST v1.1 or INRC (participants with neuroblastoma only) do not need to have tumour assessments 
repeated at the EOT Visit or during the Post-Treatment FUP. Participants who do not have documented PD at time of study treatment discontinuation will continue to undergo 
tumour assessments on their original schedule (i.e., every 9 weeks [every 63 ±7 days] from the start of study treatment for the first 12 months and then every 12 weeks [every 84 
±7 days] thereafter), until documented PD, start of alternative anticancer treatment, or discontinuation from overall study participation [e.g., death, participant’s request, or 
participant is lost to follow-up], whichever comes first). Participants who have a PR or CR while on treatment and discontinue treatment prior to the next disease assessment must 
have all appropriate follow-up disease assessments to confirm the observed response no sooner than 4 weeks (28 days) after the first observation.  
r. 
Bone scan, whole body MRI, or PET scans will be carried out at baseline for all participants in Part 1 (excluding participants with neuroblastoma) and in the Osteosarcoma 
Expansion Cohort within 84 days prior to the first dose of study treatment to detect bony sites of disease. Subsequent assessments are to be performed during the Treatment 
Period when clinically indicated (i.e., participant describes new or worsening bone pain, or other signs or symptoms of new/progressing bone metastases are present). If the 
baseline bone scan, whole body MRI, or PET scan is positive for metastatic bone disease, a repeat assessment is required for confirmation of PR or CR. 
s. 
Bone marrow assessments obtained per the standard of care prior to enrolment into the study do not need to be repeated and are acceptable to use as baseline evaluations if 
obtained within 28 days prior to the first dose of study treatment. 
u. 
AEs will be collected until 30 days after the last dose of study treatment. SAEs will be collected until 90 days after the last dose of study treatment (or to a minimum of 30 days 
after the last dose of study treatment if the participant starts alternative anticancer treatment). However, any SAEs assessed as related to study participation or related to study 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 40 of 213 
treatment will be recorded through the FUP Assessment Period. AESIs must be recorded on the eCRF. AESI collection periods are described in Section 8.3.6. Any pregnancies 
that occur in female participants within 180 days after the last dose of study treatment or in partners of male participants within 90 days after the last dose of study treatment are to 
be reported as described in Section 8.3.5. Pregnancies occurring more than 180 days after last dose of study treatment with an associated SAE (considered causally related to the 
study treatment by the Investigator) will follow the SAE reporting requirements. All AEs and SAEs will be followed, regardless of start of alternative anticancer therapy, until the 
event is resolved, stabilised, or otherwise explained; or until the participant has withdrawn consent to the study overall, is lost to follow-up (as defined in Section 7.4), or has died. 
v. 
Blood samples (single sample for all analytes) for serum dostarlimab PK and/or ADA and neutralising antibodies (NAb) will be collected from participants during Cycle 1 at the 
following time points relative to the start of the dostarlimab infusion: Cycle 1 Day 1 at Predose (PK, ADA, and NAb) and 1 ± 0.5 hours postdose (PK only), Cycle 1 Day 8 at 168 ± 
12 hours postdose (PK, ADA, and NAb), and predose on Cycle 2 Day 1 (predose sample must be collected within 12 hours prior to infusion) (PK, ADA, and NAb). Blood samples 
for serum dostarlimab PK, ADA, and NAb will also be collected at the following time periods: predose in Cycles 4 and 6, every 6 cycles thereafter up to 2 years, and the EOT Visit. 
In addition, blood samples for serum dostarlimab ADA and NAb will be collected at the Safety Follow-up Visit (30 days post-treatment) and at the first Follow-up Visit (90 days 
post-treatment). PK, ADA, and NAb samples will be drawn at the same time points and in the same collection, except as noted. 
w. The maximum blood volume for each sample for PK, ADA and NAb and exploratory biomarker assessments is 0.8 mL/kg, and the maximum total blood volume allowed for PK, 
ADA, and NAb, and exploratory biomarker assessments is 1.8 mL/kg per 3-week treatment cycle. Blood samples should be collected in order of priority as outlined in Section 8.2. 
x. 
Blood samples for plasma niraparib and 
 (single sample for both analytes) will be collected from participants during Cycle 1 Day 1 at 2.5 and 
7 hours after the first dose of niraparib, predose on Cycle 1 Day 8, predose on Cycle 2 Day 1, and Cycle 2 Day 1 at 5 hours after niraparib dose. Additional niraparib PK sampling 
is to be performed after a niraparib dose increase due to a birthday or after a niraparib dose modification due to a weight increase or decrease. (These additional PK samples will 
be taken on Day 1 in the first cycle after the dose change at 2.5 and 7 hours postdose, predose on Day 1 of the second cycle after the dose change, and at 5 hours after the 
niraparib dose on Day 1 of the second cycle after the dose change). Note: Predose samples must be collected within 2 hours prior to dosing; Cycle 1 Day 1 2.5 hour samples must 
be collected at the scheduled time ±0.5 hour and other samples must be collected at the scheduled time ±2 hours. 
y. 
 
. Blood 
samples should be collected in order of priority as outlined in Section 8.2. 
 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 41 of 213 
Table 4: 
Tumour Assessment Flowchart 
Tumour 
Assessment 
Screening 
Period 
Treatment 
Period 
Confirmation 
of Responsea 
Post-Treatment 
Follow-Up 
CT or MRI of 
chest, abdomen, 
pelvis, and any 
additional sites as 
clinically 
indicated 
Required 
Required, 
including sites 
of any other 
tumour lesions 
identified at 
baseline and of 
any additional 
sites as clinically 
indicated  
Required, 
including sites 
of any other 
tumour lesions 
identified at 
baseline 
If PD has been 
documented: 
Not required 
If PD has not 
been 
documented: 
Required, 
including sites 
of any other 
tumour lesions 
identified at 
baseline 
Brain scan (IV 
contrast-enhanced 
MRI [preferred] 
or IV contrast-
enhanced CT) 
Required for 
participants 
with previously 
treated brain 
metastases 
Not required 
unless clinically 
indicated 
Required if 
baseline scan 
was positive 
Not required 
unless clinically 
indicated 
MIBG-
SPECT/CT for 
participants with 
MIBG-avid 
tumours or FDG-
PET/CT as the 
alternative 
modality for 
participants 
whose tumours 
do not 
concentrate 
MIBG 
(Participants with 
neuroblastoma 
only) 
Required 
Required 
Required 
If PD has been 
documented: 
Not required 
If PD has not 
been 
documented: 
Required 
Bone scan, whole 
body MRI, or 
PET scan (Part 1 
[excluding 
participants with 
neuroblastoma] 
and 
Osteosarcoma 
Expansion 
Cohort)  
Required 
Not required 
unless clinically 
indicated 
Required if 
baseline scan 
was positive for 
metastatic bone 
disease 
Not required 
unless clinically 
indicated 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 42 of 213 
Tumour 
Assessment 
Screening 
Period 
Treatment 
Period 
Confirmation 
of Responsea 
Post-Treatment 
Follow-Up 
Clinical 
assessment of 
superficial lesions 
Required 
Required for 
sites of tumour 
lesions 
identified at 
baseline and any 
additional sites 
as clinically 
indicated 
Required for 
sites of tumour 
lesions 
identified at 
baseline  
Required for 
sites of tumour 
lesions identified 
at baseline, 
unless PD has 
been 
documented 
elsewhere 
Bone marrow 
aspirate and 
biopsy 
(Participants with 
neuroblastoma 
only) 
Required 
Required for 
participants with 
bone marrow 
involvement at 
screening 
Required for all 
participants 
If PD has been 
documented: 
Not required 
If PD has not 
been 
documented: 
Required for 
participants with 
bone marrow 
involvement at 
screening 
Abbreviations: CT=computed tomography; EOT=End of Treatment; FDG-PET/CT=fluorodeoxyglucose-positron 
emission tomography/computed tomography; MIBG-SPECT/CT=metaiodobenzylguanidine-single-photon 
emission computed tomography/computed tomography; MRI=magnetic resonance imaging; PD=progressive 
disease.  
Note: See Table 3 for detailed guidance on tumour assessment procedures.  
a. Participants who have a PR or CR while on treatment and discontinue treatment prior to the next disease 
assessment must have all appropriate follow-up disease assessments to confirm the observed response no sooner 
than 4 weeks (28 days) after the first observation.  
 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 43 of 213 
2. 
INTRODUCTION 
Childhood cancers are a leading cause of death in children globally, with approximately 
300 000 cancers diagnosed per year and an estimated 80 000 cancer-related deaths in 
children per year worldwide (IARC, 2017). Advancements in cancer therapies have 
improved survival over the last few decades, but survival rates have plateaued over the 
last 5 years for difficult-to-treat diseases such as acute myeloid leukaemia (AML), 
several central nervous system (CNS) tumours, neuroblastoma, and bone and soft tissue 
sarcomas. On average, approximately 20% to 30% of paediatric solid tumours will recur. 
The recurrence rate can be as high as 70% to 80% in specific tumour types, such as high-
grade glioma. Based on literature review, the expected response rate at the time of relapse 
is approximately 10% to 20% across these tumour types. This leaves a significant unmet 
medical need for the treatment of recurrent solid tumours in the paediatric population. 
2.1. 
Background on Niraparib 
Niraparib is a potent and selective inhibitor of poly (adenosine diphosphate-ribose) 
polymerase (PARP)1 and PARP2, which are key enzymes in the repair pathway for 
single-strand DNA breaks called base excision repair. When the activities of PARP1 and 
PARP2 are inhibited, single-strand DNA breaks become double-strand DNA breaks 
following DNA replication. Cancer cells are consequently forced to rely on double-strand 
DNA break repair mechanisms, in particular homologous recombination DNA repair 
(HRR), for their survival and proliferation. Defects in HRR can be caused by genetic and 
epigenetic alterations to dozens of genes, including breast cancer susceptibility gene 
(BRCA) 1 and BRCA2. PARP inhibitors are therefore capable of selectively killing a 
subset of cancer cells with deficiencies in HRR that are dependent upon an alternative 
DNA repair pathway: Base excision repair.  
2.1.1. 
Clinical Data for Niraparib 
The use of PARP inhibitors as selective anticancer agents is supported by both 
nonclinical data demonstrating that PARP inhibitors are more potent cytotoxic inducers 
in tumours with inactivation of BRCA1/2 than they are in tumours with functional BRCA, 
as well as by clinical studies showing that PARP inhibitors exhibit antitumour activity in 
patients with certain types of cancer such as breast, ovarian, prostate, and pancreatic 
cancers, including, but not limited to, those with defined BRCA mutations (Gonzalez-
Martin, 2019; Moore, 2019; Sachdev, 2019). In general, there are compelling data in 
multiple tumour types to support the efficacy of niraparib in BRCA-mutated cancers, and 
although clinical data outside of BRCA mutations are limited, there are encouraging 
preclinical and emerging clinical data to suggest that tumours with mutations in HRR 
genes or that are HRR deficient may also be highly sensitive to niraparib. In 
Study 213356 (formerly study PR305011C; NOVA), a pivotal Phase 3 trial in adult 
participants with platinum-sensitive, recurrent ovarian cancer, niraparib was observed to 
prolong progression-free survival (PFS) relative to placebo across cohorts of participants 
with germline BRCA mutations (hazard ratio [HR]=0.27, p<0.001), non-germline BRCA 
mutations (HR=0.45, p<0.001), and non-germline BRCA mutations and HRR deficiencies 
(HR=0.38, p<0.001) (niraparib IB [GSK document No. RPS-CLIN-053021]). These data 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 44 of 213 
support the hypothesis that patients without genomic BRCA mutations may still benefit 
from niraparib treatment, and it is likely that the activity of niraparib in these patients is 
driven by defects in HRR other than BRCA mutations. 
As of December 2023, niraparib is approved in over 40 countries worldwide, including 
the US, European Union, Japan, China, Switzerland, Australia, and Canada as 
maintenance treatment for women with recurrent epithelial ovarian, fallopian tube, or 
primary peritoneal cancer who are in complete or partial response to platinum-based 
chemotherapy and for the maintenance treatment of adult patients with advanced 
epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete 
response (CR) or PR to first-line platinum-based chemotherapy.  
2.2. 
Background on Dostarlimab 
Dostarlimab is a humanised monoclonal antibody (mAb) of the immunoglobulin G4 
(IgG4) subclass that binds with high affinity to programmed cell death protein 1 (PD-1) 
and blocks the interaction between PD-1 and its ligands, programmed cell death-ligand 1 
(PD-L1) and programmed cell death-ligand 2 (PD-L2).  
PD-1 is a cell surface receptor expressed on T cells that limits T-cell activation through 
binding to PD-L1 and, to a lesser extent, PD-L2 (Dong, 1999; Freeman, 2000; Ishida, 
1992; Latchman, 2001; Tseng, 2001). The PD-1/PD-L1 checkpoint serves as a negative 
regulator of T-cell activity to help control local inflammatory responses and maintain 
self-tolerance. PD-L1 is expressed constitutively on a subset of macrophages, but it is 
also known to be expressed on tumour cells (Keir, 2008). In the tumour 
microenvironment, when PD-L1 on tumour cells binds to PD-1 on activated T cells, T-
cell activation is inhibited, which prevents tumour cell killing by T cells (Chen, 2015; 
Zou, 2008). This process is called immune evasion. Blockade of the interaction between 
PD-1 and PD-L1/PD-L2 with dostarlimab in patients with solid tumours is expected to 
strengthen the functional activity of tumour-infiltrating lymphocytes and promote tumour 
cell death. 
Dostarlimab was generated using a proprietary platform that employs affinity maturation 
to select highly specific antibodies with desired functional characteristics (Bowers, 2011). 
The functional antagonist activity of dostarlimab was confirmed in a mixed lymphocyte 
reaction, demonstrating enhanced activation of T cells as measured by interleukin-2 
production upon the addition of dostarlimab (Laken, 2016). 
2.2.1. 
Clinical Data for Dostarlimab 
Dostarlimab was granted accelerated approval by the United States Food and Drug 
Administration (FDA) on 22 April 2021 with subsequent conversion to a full approval on 
09 February 2023 for the treatment of adult patients with mismatch repair-deficient 
(dMMR) recurrent or advanced endometrial cancer, as detected by an FDA-approved 
test, that has progressed on or following prior treatment with a platinum-containing 
regimen (Biologics License Application [BLA] 761,174). A Conditional Marketing 
Authorisation Application (CMAA) was granted by the European Medicines Agency 
(EMA) on 21 April 2021 with subsequent conversion to a full approval on 07 December 
2023 for use in women with dMMR/microsatellite instability-high (MSI-H) recurrent or 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 45 of 213 
advanced endometrial cancer, who have progressed on or following prior treatment with 
a platinum-containing regimen. In addition, accelerated approval was granted by the FDA 
on 17 August 2021 for dostarlimab for the treatment of patients with recurrent or 
advanced dMMR solid tumours, as determined by an FDA-approved test, that have 
progressed on or following prior treatment and who have no satisfactory alternative 
treatment options (BLA 761, 223) 
The US and European approvals were based on data from GSK study 213346 (formerly 
study 4010-01-001; GARNET), which evaluated dostarlimab monotherapy in participants 
with recurrent or advanced solid tumours who have limited treatment options and who 
had dMMR/microsatellite-instability-high endometrial cancer that progressed on or after 
a platinum-containing regimen. An objective response rate (ORR; blinded independent 
review using Response Evaluation Criteria in Solid Tumours [RECIST] v1.1) of 44.7% 
(95% CI: 34.9, 54.8) was observed (dostarlimab IB (GSK document No. RPS-CLIN-
029721). 
2.3. 
Rationale for Synergy Between PARP Inhibitors and Immune 
Checkpoint Inhibitors 
There is a strong preclinical rationale, as well as emerging clinical data, for synergy 
between PARP inhibitors and immune checkpoint inhibitors. It has been demonstrated 
that PARP inhibitors increase lymphocyte infiltration and activation in mouse tumour 
models (Huang, 2015) turning “immunologically cold” tumours into “immunologically 
hot” tumours, which are more likely to respond to anti-PD-1 therapies.  
Both intrinsic DNA repair deficiency and PARP inhibition lead to accumulation of DNA 
damage and cytoplasmic DNA, which leads to activation of the stimulator of interferon 
genes (STING) pathway (Ding, 2018; Hartlova, 2015; Parkes, 2017). The STING 
pathway in turn contributes to antitumour immune responses in cancer [reviewed in 
(Barber, 2015; Li, 2018)]. 
Recently, PARP inhibitors have been shown to elevate PD-L1 expression (Jiao, 2017). 
This finding suggests that the immunomodulatory effects of PARP inhibitors could be 
muted by the expression of PD-L1, and that blocking PD-1 or PD-L1 may enhance the 
ability of niraparib to induce durable responses. Nonclinical studies conducted in 
syngeneic murine models have demonstrated the increased efficacy of an 
anti-PD-1/niraparib combination over either agent alone, and the combination was well 
tolerated in these studies (Huang, 2015; Meade, 2016; Mills, 2017; Xing, 2006).  
Finally, in Study 213363 (formerly study 3000-PN162-01-001; TOPACIO) in adults with 
platinum-resistant ovarian cancer and triple-negative breast cancer, the combination of 
niraparib and an anti-PD-1 inhibitor (pembrolizumab) demonstrated efficacy in a broad 
range of biomarker-defined subpopulations including those participants with normal 
BRCA alleles and without molecular evidence of HRR deficiency, with improved activity 
as compared to either agent alone (Vinayak, 2019). Safety data were consistent with the 
safety profiles described for either treatment as monotherapy. Furthermore, the 
combination was shown to be tolerable with no new safety signals identified 
(Konstantinopoulos, 2017). The incidence of immune-related TEAEs with dostarlimab 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 46 of 213 
was comparable to that observed with pembrolizumab, dostarlimab and pembrolizumab 
have the same molecular target and therefore mechanism of action, and results from 
GARNET suggest the safety and efficacy of dostarlimab are comparable to those of 
pembrolizumab. Niraparib is currently being investigated in combination with 
dostarlimab in several adult disease settings, including a registrational study (Study 
213359; formerly study 3000-03-005; FIRST) evaluating maintenance with niraparib and 
dostarlimab as part of a treatment plan following first-line treatment in adult participants 
with either Stage 3 or 4 nonmucinous epithelial ovarian cancer. 
2.4. 
Rationale for Tumour Type   
The tumour types that are targeted for niraparib clinical development in adults (eg, 
ovarian, breast, prostate, and lung cancer) do not occur or are extremely rare in children. 
In paediatric malignancies, mutations in the HRR pathway are infrequent (Harttrampf, 
2017), and there is no single tumour type that would be characteristic of these mutations. 
However, there are other mechanisms that could lead to deficiency in HRR, thereby 
predisposing the tumour to respond to PARP inhibitors. A method to identify tumours 
with homologous recombination deficiency is through genome-wide mutational 
signature. An example of one of these mutational signatures is mutational signature 3, 
present in a relatively high percentage of paediatric solid tumours across multiple tumour 
types (Gröbner, 2018). Mutational signature 3, also henceforth referred to as BRCAness 
mutational signature, in turn has been linked with the failure of double-strand DNA break 
repair by HRR (Alexandrov, 2013). Based on a recent report of whole genome 
sequencing of over 500 paediatric tumours, the following tumour types exhibit the 
BRCAness mutational signature in approximately >50% of cases: Osteosarcoma, 
adrenocortical carcinoma, neuroblastoma, medulloblastoma, high-grade glioma, 
rhabdomyosarcoma (Gröbner, 2018; Kovac, 2015, PedPanCan), and Ewing sarcoma 
(personal communication with Dr Stefan Pfister, 16 May 2018). Osteosarcoma and 
neuroblastoma, specifically, exhibit the BRCAness mutational signature in >90% of cases 
(Gröbner, 2018). Additionally, nonclinical data support the rationale for PARP inhibitor 
activity not necessarily related to the presence of mutational signature 3 in many of the 
aforementioned tumour types, including osteosarcoma (Chornenkyy, 2015; Engert, 2017; 
Engert, 2015; Garnett, 2012; Kovac, 2015; Smith, 2011). 
 
 
 
 
  
2.5. 
Rationale for Current Study 
Historically, the response rates observed in early-phase studies of single agents used to 
treat relapsed paediatric tumours are lower than the response rates observed using 
combination therapies (Waligora, 2018). Data on the activity of single agent PARP 
inhibitors in paediatric tumours hold limited promise (Choy, 2014; Chugh, 2017; 
Federico, 2017). Combining PARP inhibitors with cytotoxic chemotherapy has been 
limited by overlapping toxicity profiles that result in intermittent dosing of the PARP 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 47 of 213 
inhibitors, which may reduce their efficacy (Chen, 2016; Chugh, 2017; Halford, 2017; 
Kurzrock, 2014). On the other hand, combining PARP inhibitors with biologic agents has 
been well tolerated and has allowed dosing of the PARP inhibitor at the single agent 
maximum tolerated dose (MTD) level (Dean, 2012; Konstantinopoulos, 2017; Lee, 2017; 
Liu, 2013; Mirza, 2017). The activity of immune checkpoint inhibitors in paediatric solid 
tumours as a single agent has also been limited (Geoerger, 2017; Kabir, 2018; Kara L. 
Davis, 2017). The activity of immune checkpoint inhibitors in adult indications has been 
linked to the expression of PD-L1 in the tumour as well as to the overall TMB. Similar to 
the BRCAness mutational signature, there is no single histologic subtype of paediatric 
tumours with high TMB (Gröbner, 2018) or PD-L1 expression (Geoerger, 2017). 
However, tumour types with these attributes, such as osteosarcoma, high-grade glioma, 
rhabdomyosarcoma, adrenocortical carcinoma, medulloblastoma, and neuroblastoma, 
overlap with tumours with a high BRCAness mutational signature (Geoerger, 2017; 
Gröbner, 2018). 
This initial clinical study in the paediatric population will therefore evaluate the 
combination of a PARP inhibitor, niraparib, with the PD1 inhibitor, dostarlimab. The 
study will be conducted to determine the recommended Phase 2 dose (RP2D) and 
evaluate the pharmacokinetics (PK), safety, and efficacy of niraparib in combination with 
dostarlimab in paediatric participants ≥6 months to <18 years of age with recurrent or 
refractory solid tumours that are known to have 
 
 
 
 The study will be conducted as a two-
part dose escalation, followed by Cohort Expansion. In Part 1A, the RP2D of the 
niraparib tablet formulation and dostarlimab will be determined, unless the need arises 
for use of the tablet for oral suspension 
 of niraparib for evaluation of a lower 
dose. Part 1B will determine the PK parameters of the 
 of niraparib in combination 
with dostarlimab, with the objective of determining the RP2D of the niraparib 
 in 
combination with dostarlimab for the intended paediatric population (i.e., participants not 
able to swallow the tablet formulation). Part 2 will consist of disease-specific expansion 
cohorts of participants, including participants with osteosarcoma or neuroblastoma, to 
evaluate the anticancer activity of the RP2D of niraparib and dostarlimab. The details for 
Part 2 of this study are presented in each cohort-specific supplement, as applicable. 
2.6. 
Benefit Risk Assessment 
2.6.1. 
Risk Assessment:  
2.6.1.1. 
Niraparib Monotherapy 
More detailed information about the known and expected risks and reasonably expected 
adverse events (AEs) of niraparib observed in adults may be found in the current version 
of the niraparib Investigator’s Brochure (niraparib IB (GSK document No. RPS-CLIN-
053021). Risk minimisation measures for this study (such as dose reduction and 
discontinuation) are discussed in Table 5, Section 4.7.2.1 (including Table 9 and 
CCI
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 48 of 213 
Table 10), and Section 6.8.1. The SoA table in Section 1.3 also indicates safety follow-up 
visits. 
Table 5: 
Summary of Risks and Mitigations for Niraparib 
Abbreviation: AML=Acute myeloid leukaemia; MDS=Myelodysplastic syndrome; PARP=poly (adenosine 
diphosphate-ribose) polymerase. 
 
2.6.1.2. 
Dostarlimab Monotherapy  
More detailed information about the known and expected risks and reasonably expected 
AEs of dostarlimab observed in adults may be found in the current version of the 
dostarlimab Investigator’s Brochure (GSK document No. RPS-CLIN-029721). Risk 
minimisation measures for this study (such as dose reduction and discontinuation) are 
discussed in Table 6, Section 4.7.2.2 (including Table 11), and Section 6.8.1. The SoA 
table in Section 1.3 also indicates safety follow-up visits. 
 
Risks of Clinical 
Significance (Identified or 
Potential) 
Summary of Data/Rationale 
for Risk 
Mitigation Strategy 
Thrombocytopenia 
Anaemia 
Neutropenia including 
neutropenic infection and 
sepsis. 
Based on nonclinical and 
clinical observations as well 
as identified risk with PARP 
inhibitor, niraparib  
Protocol provides guidelines 
for monitoring haematologic 
labs and adverse reactions 
(Section 4.7.2.1, Table 10)  
Protocol provides guidance for 
dose modification and 
discontinuation of study 
(Section 4.7.2.1, Table 10)  
Hypertension 
Cases reported with niraparib 
Protocol provides monitoring 
and stopping criteria for 
discontinuation of study 
treatment (Section 4.7.2.1, 
Table 9) 
MDS or AML, along with 
other second primary 
malignancy (new 
malignancies other than 
MDS or AML) 
Based on nonclinical and 
clinical observations as well 
as identified with PARP 
inhibitor, niraparib 
Protocol provides monitoring 
and stopping criteria for 
discontinuation of study 
treatment (Section 4.7.2.1, 
Table 10) 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 49 of 213 
Table 6: 
Summary of Risks and Mitigations for Dostarlimab 
Abbreviations: AE=adverse event; imAE=immune-mediated adverse event; IRR=infusion-related reaction; 
mAb=monoclonal antibody; PD-(L)1=programmed cell death protein 1/(programmed death-ligand 1). 
 
2.6.1.3. 
Niraparib plus Dostarlimab Combination Safety and Efficacy 
In addition to current paediatric study 213406, GSK is evaluating the efficacy and safety 
of dostarlimab in combination with niraparib in the following studies in adults: 
• Study 213357 (OPAL, formerly known as 3000-02-005): A Phase 2 multicohort 
study to evaluate the safety and efficacy of novel treatment combinations 
(niraparib at 300 mg or 200 mg plus dostarlimab in combination with 
bevacizumab) in patients with recurrent ovarian cancer (NCT03574779). 
• Study 213361 (RUBY, formerly known as 4010-03-001): A Phase 3 multicohort 
study to evaluate dostarlimab plus carboplatin-paclitaxel versus placebo plus 
carboplatin-paclitaxel in participants with recurrent or primary advanced 
endometrial cancer. Part 2 includes participants receiving dostarlimab plus 
carboplatin-paclitaxel followed by dostarlimab plus niraparib (NCT03981796). 
GSK evaluated the efficacy and safety of dostarlimab in combination with niraparib in 
the following studies in adults: 
Risks of Clinical 
Significance (Identified or 
Potential) 
Summary of Data/Rationale 
for Risk 
Mitigation Strategy 
Immune-mediated AEs 
(imAEs; including 
pneumonitis, colitis, 
hepatitis, endocrinopathies, 
immune-related skin 
adverse reactions, nephritis 
and other imAEs) 
imAEs, which may be severe 
or fatal, can occur in patient 
treated with monoclonal 
antibodies directed against 
immune checkpoints, 
including dostarlimab. While 
imAEs usually occur during 
treatment, 
symptoms can also manifest 
after discontinuation of 
treatment. imAEs may occur 
in any organ or tissue and 
may affect more than one 
body system simultaneously. 
Participants with the following 
medical history are ineligible 
for this study: 
• 
Toxicity related to prior 
immunotherapy leading to 
study treatment 
discontinuation 
• 
Active autoimmune disease 
• 
Severe hypersensitivity to 
dostarlimab, its 
components, or its 
excipients. 
Established management 
algorithms for imAEs: refer to 
Table 11 and Table 12 for 
further details on the 
identification, evaluation, and 
management of toxicities, 
including cumulative effects, 
with a potential immune 
etiology. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 50 of 213 
• Study 213351 (IOLite, formerly known as 3000-01-002): A Phase 1b dose finding 
study of niraparib, cobolimab, bevacizumab, and platinum-based doublet 
chemotherapy in combination with dostarlimab in patients with advanced or 
metastatic cancer. Two parts of the study (Part A and C) include niraparib and 
evaluated the safety and preliminary efficacy of niraparib in combination with 
dostarlimab or niraparib plus bevacizumab in combination with dostarlimab in 
patients with advanced or metastatic cancer (NCT03307785). 
• Study 213352 (JASPER, formerly known as 3000-02-001): A Phase 2, multiarm 
study of niraparib administered alone and in combination with a PD-1 inhibitor 
(pembrolizumab or dostarlimab) in patients with non-small cell lung cancer 
(NCT03308942). 
• Study 213353 (MOONSTONE, formerly known as 3000-02-006): A Phase 2 
open-label, single-arm study to evaluate the efficacy and safety of the 
combination of niraparib and dostarlimab in patients with platinum-resistant 
ovarian cancer (NCT03955471). 
• Study 213355 (FIRST, formerly known as 3000-03-005): A randomised, double-
blind, Phase 3 comparison of platinum-based therapy with dostarlimab and 
niraparib versus standard of care platinum-based therapy as first-line treatment of 
Stage III or IV non-mucinous epithelial ovarian cancer (NCT03602859). 
Safety 
As of March 2023, the safety and tolerability of niraparib has been evaluated in >2000 
participants with advanced cancers who have received at least 1 dose of niraparib, of 
whom over 250 received niraparib in combination with a PD-1 inhibitor (either 
dostarlimab or pembrolizumab) (niraparib IB [GSK document No. RPS-CLIN-053021]). 
As expected, considering the well-established safety profile of PD-1 inhibitors, including 
dostarlimab and pembrolizumab, and the safety profile of niraparib, no new safety signals 
were observed with the combination of niraparib and a PD-1 inhibitor. Overall, the safety 
profiles observed to date are consistent with the safety profile of either niraparib or 
dostarlimab monotherapy. 
Efficacy 
Niraparib and Dostarlimab 
Efficacy results from the IOLite study demonstrated clinical benefit with the treatment 
combination of dostarlimab and niraparib. Although the sample size was small, 
encouraging preliminary evidence of antitumour activity was demonstrated in the 
participants treated with dostarlimab in combination with niraparib. In general, 
pharmacokinetic (PK) analysis following administration of dostarlimab plus niraparib 
showed no appreciable differences in systemic exposure between treatments.  
Niraparib and Pembrolizumab 
Efficacy has also been demonstrated for niraparib in combination with the PD-1 inhibitor 
pembrolizumab (a PD-1 inhibitor compared to which dostarlimab is proposed to have 
similar safety and activity characteristics) in the TOPACIO (Study 213363) and JASPER 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 51 of 213 
(Study 213352) studies. In the TOPACIO study, the combination demonstrated 
antitumour activity across biomarker-defined subpopulations including patients with 
normal BRCA alleles and without molecular evidence of HRR (Konstantinopoulos , 2017; 
Vinayak 2019). Furthermore, the combination was shown to be tolerable with no new 
safety signals identified (Konstantinopoulos , 2017; Vinayak , 2019).  
The JASPER study also demonstrated antitumour activity in adults with non-small cell 
lung cancer with the combination of niraparib and pembrolizumab with the highest 
response rate observed in participants with high PD-L1 expression (Ramalingam, 2022; 
GSK document No. RPS-CLIN-053021). Like TOPACIO, the combination was tolerable 
and no new safety signals were observed. 
2.6.2. 
Overall Benefit: Risk Conclusion 
As demonstrated in the NOVA study for monotherapy niraparib and in the GARNET 
study for monotherapy dostarlimab, clinical evidence supports a positive risk/benefit 
profile for each agent individually when used as monotherapy. Both agents have 
displayed antitumour activity and have manageable safety profiles that are well-
established by extensive clinical trial and post-marketing experience. Clinical evidence 
on the combination of niraparib and dostarlimab in the adult population demonstrates a 
manageable safety profile with signs of synergistic activity in refractory/recurrent adult 
populations irrespective of mutational status. Antitumour activity has been reported from 
IOLite for the combination of niraparib plus dostarlimab and from TOPACIO for the 
combination of niraparib and pembrolizumab in the targeted patient populations. 
In summary, the available efficacy and safety evidence from the combination of niraparib 
and dostarlimab in the adult population suggests potential therapeutic benefit for the 
treatment of recurrent solid tumours in the paediatric population. Therefore, it is 
warranted to explore the safety and efficacy of the combination at the appropriate dose as 
determined in the planned Part 1 in a trial of paediatric participants with high unmet 
medical need. 
Information from this study will inform the Sponsor of the safety, tolerability, and initial 
signs clinical activity of the proposed combination in the specified tumour types. 
2.6.3. 
Dose Justification 
2.6.3.1. 
Niraparib Dosing  
Niraparib Dosing in Adults 
The recommended dose of 
 for first-line maintenance treatment of ovarian 
cancer is 
 for participants weighing <77 kg or with a platelet 
count <150 000/μL or 
 for participants weighing ≥77 kg and with a platelet count 
≥150 000/μL based on the PRIMA study. The recommended dose for second-line 
maintenance treatment of ovarian cancer is 
. In univariate exposure-response 
analyses of the PRIMA study, increasing niraparib exposure was associated with 
increasing risk of thrombocytopenia, anaemia, neutropenia, hypertension, and fatigue 
AEs. 
CCI
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 52 of 213 
Niraparib Dosing in Children 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 53 of 213 
2.6.3.2. 
Dostarlimab Dose 
Dostarlimab Dosing in Adults 
The currently approved adult dosing regimen for 
 
 for subsequent 
cycles until disease progression or unacceptable toxicity based on study 213346 
(GARNET) for endometrial cancer in the US and EU and dMMR pan-tumour in the US. 
Based on exposure-response analysis of the data from the GARNET study, there was no 
statistically significant relationship between dostarlimab PK exposure (area under the 
plasma concentration-time curve [AUC], maximum plasma concentration [Cmax], and 
minimum plasma concentration [Cmin] during the first dosing interval [21 days]) and 
overall response rate after accounting for patient and disease-related covariates. From the 
exposure-safety analysis, dostarlimab PK exposures (AUC, Cmax, and Cmin) during the 
first 6 weeks after the first dose (i.e., 42 days) did not have a statistically significant or 
clinically relevant relationships with any of the 5 most prevalent drug-related AEs as 
assessed by Investigators (asthenia, diarrhoea, fatigue, hypothyroidism, and nausea) 
(dostarlimab IB GSK Document No. RPS-CLIN-029721). 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 54 of 213 
 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 55 of 213 
3. 
STUDY OBJECTIVES AND ENDPOINTS 
The objectives and endpoints for Part 1 of this study are detailed as follows in Table 8. 
The study design and endpoints for Part 2 of this study are detailed in the separate cohort-
specific supplements; however, the common objectives are summarised as follows in 
Table 8. 
Table 8: 
Objectives and Endpoints for Study 213406 
Objectives 
Endpoints 
Primary 
Part 1A: Establish the RP2D of the 
combination of niraparib tablet and 
dostarlimab in paediatric participants 
Assess the incidence of DLTs by study part 
and cohort for the DLT-evaluable Population. 
Part 1B: Establish the RP2D of the 
combination of 
 
 in paediatric participants 
Assess the incidence of DLTs by study part 
and cohort for the DLT-evaluable Population. 
Part 2: Assess the safety, tolerability, and the 
antitumour activity of the combination of 
niraparib and dostarlimab 
Please refer to the separate cohort-specific 
supplements for this information. 
Secondary 
Evaluation of measures of anticancer activity 
in paediatric participants 
ORR based on Investigator assessment is 
defined as the proportion of participants with 
a BOR of confirmed CR or PR as determined 
by the Investigator using RECIST v1.1 or 
INRC (for participants with neuroblastoma 
only). 
DOR is defined as the time from first 
documentation of confirmed response (CR or 
PR) until the time of first documented PD by 
RECIST v1.1 or INRC (for participants with 
neuroblastoma only) based on Investigator 
assessment or death (whichever occurs first). 
Part 2: Please refer to the separate cohort-
specific supplements for this information. 
Evaluation of the safety and tolerability of the 
combination of 
 
 in paediatric participants 
Assess the incidence of TEAEs, SAEs, 
imAEs, TEAEs leading to death, and AEs 
leading to treatment discontinuation. AE 
evaluation period is while participants are on 
treatment or up to 90 days after the last dose 
of study treatment.  
Characterisation of the PK of the combination 
of niraparib and dostarlimab in paediatric 
participants 
Niraparib and dostarlimab concentrations; PK 
parameters of niraparib and dostarlimab, if 
appropriate. 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 56 of 213 
Objectives 
Endpoints 
Assessment of the immunogenicity of 
dostarlimab in paediatric participants 
Rate and extent of ADA to dostarlimab. 
Exploratory 
Abbreviations: ADA=antidrug antibody(ies); AE=adverse event; BOR=best overall response; 
CR=complete response; 
; DLT=dose limiting toxicity; DOR=duration of 
response; INRC=International Neuroblastoma Response Criteria; imAE=immune-mediated adverse event; 
ORR=objective response rate; PD=progressive disease; PK=pharmacokinetic(s); PR=partial response; 
RECIST=Response Evaluation Criteria in Solid Tumours; RP2D=recommended Phase 2 dose; 
SAE=serious adverse event; SoA=schedule of activities; TEAE=treatment-emergent adverse event; 
 
  
CCI
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 57 of 213 
4. 
OVERALL DESIGN 
This is a master protocol for a Phase 1, multicentre, open-label, dose escalation study 
(Part 1) with a Safety Run-in and Cohort Expansion component (Part 2) (Figure 1). The 
study will consist of an initial dose escalation portion conducted in participants with 
tumours that are known to have a 
 
 
 
 Part 1A, a dose escalation to determine the RP2D of the 
combination of niraparib tablets and dostarlimab, included participants who were able to 
swallow the 
 niraparib tablets and who had a body weight of ≥20 kg. Part 1B, a 
dose escalation to determine the RP2D of the combination of 
 
, under Protocol Amendment 03 (or earlier), included participants who could 
not swallow the 
 or who had a body weight of <20 kg. In Part 2 
of the study under Protocol Amendment 03, the RP2D regimen established in Part 1 was 
evaluated for efficacy and safety in disease-specific expansion cohorts including 
participants ≥20 kg and able to swallow 
. Under Protocol 
Amendment 05, participants will receive 
, and eligibility 
for Part 1B is no longer dependent upon participant weight or ability to swallow niraparib 
tablets. Instead, 
 
 
  
A review of safety data and available preliminary PK data will be conducted by the 
Sponsor and Investigators following completion of the DLT observation periods in Part 
1A, Part 1B, and the Part 2 Safety Run-in. Determination of the specific RP2D will be 
based on review of safety and PK data. An mTPI-2 dose escalation design will be used 
for the evaluation of safety at each dose level (Appendix 10). 
 
 
 Otherwise, 
participants requiring a niraparib dose reduction from 
 were to be required to 
discontinue study treatment (both drugs).  
The study designs for the Part 2 Safety Run-in and for the Part 2 expansion cohorts are 
described in each of the cohort-specific supplements. 
4.1. 
Part 1 Dose Escalation Design 
 
 
 
 
 
 
 
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 58 of 213 
 
 
 
 
 
 
 
 
 
4.1.1. 
Part 1A Design 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Participants in Cohort 0 were dosed in a staggered fashion. At this dose level, no more 
than 3 participants were allowed to receive an initial dose of study treatment until the first 
3 participants had all completed at least 1 cycle of study treatment and the resulting data 
from all 3 participants had been reviewed. This was to ensure an adequate interval for 
observation and assessment of potential acute AEs. Although not needed, dosing strategy 
for subsequent participants after the initial 3 participants dosed was to have been made by 
the Dose Escalation Committee (DEC) if >1 DLT was observed in the first 3 participants 
within the first cycle of treatment for each participant (see Appendix 1 for details 
regarding the DEC). 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 59 of 213 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 60 of 213 
If Cohort 0 
 was deemed safe based on 
the mTPI-2 parameters described above, 2 cohorts were to have opened: Cohort 1A and 
Cohort 1B. In Cohort 1A, 
 
 In Cohort 1B, niraparib was to be escalated to dose level 2 
(DL2; no more than 2 times DL1) as determined based on the observed DLTs and PK 
values, if available, from Cohort 0, and 
. If both 
Cohorts 1A and 1B were considered safe, then Cohort 2 
 
 was to be opened. If the Cohort 2 dose level was deemed 
safe, this may have been considered the RP2D for the niraparib tablet formulation. If the 
dose level from Cohort 2 was not cleared for use, the RP2D was to be the dose level from 
Cohort 1B. If only 1 cohort of Cohorts 1A and 1B was deemed safe, then that dose level 
was to be considered the RP2D. Lastly, if neither Cohort 1A nor 1B was deemed safe, the 
combination dose level from Cohort 0 was to be the RP2D. 
If Cohort 0 was deemed too toxic based on the mTPI-2 parameters described above, a 
clinical assessment of the observed DLTs was to be done. If it was determined by the 
Sponsor and the Site Investigators that all the DLTs observed could be attributed to an 
immune checkpoint inhibitor (ICI), Cohort -1A, 
 
, was to be opened (Figure 3, B. Dose De-
escalation). If not all DLTs observed could be attributed to an ICI, Cohort -1B, with 
niraparib de-escalated to dose level -1 (DL-1; determined based on the observed PK data 
in Cohort 0 and availability of an alternative dosing option[s], including the TfOS) and 
dostarlimab 
, was to be opened. 
If Cohort -1A 
 was deemed safe based 
on the mTPI-2 parameters described above, the dose level from Cohort -1A was to be 
established as the RP2D. If Cohort -1A was not cleared and it was determined by the 
Sponsor and the Site Investigators that all the DLTs observed could be attributed to an 
ICI, the study would not continue as designed. If Cohort -1A was not cleared and it was 
determined by the Sponsor and the Site Investigators that not all the DLTs observed 
could be attributed to an ICI, Cohort -2, evaluating niraparib at DL-1 and dostarlimab at 1 
mg/kg Q3W, would be opened. If Cohort -2 was deemed safe, the dose level from Cohort 
-2 would be the RP2D. If Cohort -2 was not cleared, the study would not continue as 
designed. Alternate dosing option(s), such as use of a lower dose with the TfOS, may also 
have been implemented for niraparib, if appropriate. 
If Cohort -1B 
 was deemed safe based 
on the mTPI-2 parameters described above, the dose level from Cohort -1B was to be 
established as the RP2D. If Cohort -1B was not cleared and it was determined by the 
Sponsor and the Site Investigators that all the DLTs observed could be attributed to an 
ICI, Cohort -2 evaluating 
, was to be 
opened. If Cohort -1B was not cleared and it was determined by the Sponsor and the Site 
Investigators that not all the DLTs observed could be attributed to an ICI, the study 
would not continue as designed. If Cohort -2 was deemed safe, the dose level from 
Cohort -2 was to be considered the RP2D. If Cohort -2 was not cleared, the study would 
not continue as designed. Alternate dosing option(s), such as use of a lower dose with the 
TfOS, may also have been implemented for niraparib, if appropriate. 
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 61 of 213 
Once the RP2D of niraparib and dostarlimab was established in Part 1A for 
 
, Part 2 (disease-specific expansion cohorts, as described in cohort-
specific supplements to this protocol) was opened to accrual for a limited number of 
participants who were able to swallow the 
. In addition, Part 1B 
opened once the RP2D was established in Part 1A and the niraparib TfOS was available 
(Section 4.1.2). 
4.1.2. 
Part 1B Design  
Figure 4: 
Part 1B Study Schema Under Protocol Amendment 03 (or Earlier) 
 
Abbreviations: DL-1=dose level -1; DL2=dose level 2; PK=pharmacokinetic(s); popPK=population pharmacokinetics; 
RP2D=recommended Phase 2 dose. 
a. 
The study will not continue as designed. Alternate niraparib schedules (such as dosing during 2 of 3 weeks) 
and/or conversion to body surface area-based dosing may also be implemented for niraparib, if appropriate. 
Dose level cleared, and niraparib escalation not recommended based on PK 
Dose level cleared, but niraparib escalation recommended based on PK  
Dose level not cleared
Cohort 1:
Niraparib Dose Based 
on popPK
Dostarlimab RP2D from 
Part 1A
Cohort -1:
Niraparib DL-1 (dose 
decrease guided by PK)
Dostarlimab RP2D from 
Part 1A
RP2D is 
Cohort 1
Cohort 2:
Niraparib DL2 (dose 
increase guided by PK)
Dostarlimab RP2D from 
Part 1A
Stopa
RP2D is 
Cohort 2
RP2D is 
Cohort -1
Niraparib 
PK
assessment
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 62 of 213 
Following the enrolment pause and review and analysis of clinical, safety and PK data for 
all study participants, Part 1B will restart using a modified 
 
 described in Section 2.6.3.1 and Table 7. 
 
 
 
The planned dose escalation schema for the reopened Part 1B is in Figure 5. PK 
evaluations will be performed in at least 6 participants in each cohort unless enrolment 
into the cohort is closed prematurely due to toxicity.  
Enrolment into each Part 1B cohort will take participant age into consideration, with the 
intent to distribute enrolment across 3 age categories: 6 months to <2 years; ≥2 years to 
<6 years; and ≥6 years to <8 years. Enrolment into each cohort will be limited to no more 
than 4 participants aged 6 years or older out of the first 6 participants. The remaining 2 
participants out of the first 6 participants in each cohort must be younger than age 6 
years. 
Once enrolment into Cohort A has reached the target 6 participants (or 8, if necessary), 
safety and PK data will be evaluated, and the decision will be made to open either Cohort 
B or Cohort C. Decision steps are described below.  
If Cohort B is to be opened, but at least 1 participant from the youngest age category 
(6 months to <2 years) has not been enrolled in Cohort A, the first potential participant 
aged 6 months to <2 years to join the study will be enrolled into Cohort A to permit 
safety evaluation of the starting niraparib and dostarlimab dose levels. Data from this ≥6 
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 63 of 213 
months to <2 years of age participant will not contribute to the decision for the next dose 
level, but may be used to evaluate safety and PK within that age category. 
The DEC will review all relevant safety and PK data immediately after all participants 
treated in the same dose cohort have passed the DLT period. For Cohort A, the DEC may 
potentially initiate data review as soon as 2 participants have been enrolled and observed 
for the DLT period, depending on the occurrence of DLTs and/or Grade ≥3 
thrombocytopenia. 
Cohort A 
Participants in Cohort A will be dosed in a staggered fashion, meaning, no more than 
2 participants will be allowed to receive the initial dose of study treatment until each 
participant has completed 2 cycles of study treatment and the resulting clinical safety data 
from both participants have been reviewed. This is to ensure an adequate interval for 
observation and assessment of tolerability of the dose.  
• 
If DLTs or Grade ≥3 thrombocytopenia are observed in ≤1 of the first 2 dosed 
participants and it is deemed safe to proceed by the study team, a third participant 
will be allowed to receive the initial dose of study treatment. No additional 
participants will be allowed to receive study treatment until the third participant has 
completed at least 2 cycles of study treatment and the resulting data have been 
reviewed by the study team. 
• 
If DLTs or Grade ≥3 thrombocytopenia are observed in <2 of the first 3 dosed 
participants, Cohort A will continue to enrol up to 6 evaluable participants. If a DLT 
is observed in 2 of the first 6 dosed participants, Cohort A will be expanded to 8 
DLT-evaluable participants.  
• 
If DLTs or Grade ≥3 thrombocytopenia are observed in both of the first 2 dosed 
participants, Part 1B will be paused. Safety data for the first 2 dosed participants will 
be reviewed by the DEC. The dosing strategy for subsequent participants will be 
determined by the DEC. (See Appendix 1 for details regarding the DEC.) 
• 
If DLTs or Grade ≥3 thrombocytopenia are observed in 2 of the first 3 dosed 
participants, Part 1B will be paused and safety data and PK data will be reviewed by 
the DEC. The dosing strategy for subsequent participants will be determined by the 
DEC.  
• 
If 8 participants have been enrolled and if DLTs are observed in 3 or more of 8 DLT-
evaluable participants, the dose level will not be cleared and the decision about the 
next dose level will be made by the DEC (i.e., to proceed to Cohort C with niraparib 
DL-1). 
If Cohort A is deemed safe based on the mTPI-2 parameters described previously, results 
of the niraparib PK assessment will be taken into consideration when determining the 
RP2D. If the PK exposure for the niraparib TfOS is consistent with the exposure 
observed in adults, the niraparib dose in Cohort A will be the basis of determining the 
RP2D for the TfOS.  

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 64 of 213 
If the PK exposure for dostarlimab in Cohort A is consistent with the exposures observed 
in adults, then the dose level of niraparib and of dostarlimab from Cohort A will be 
determined to be the RP2D.  
If the PK exposures observed in Cohort A with the niraparib TfOS are substantially lower 
than those observed in adults, a dose escalation cohort (Cohort B) will be opened.  
Cohort B 
The dose of niraparib for Cohort B will be determined based on the PK evaluation in 
Cohort A and the dose level of dostarlimab will remain the same as in Cohort A.  
If Cohort B is deemed safe based on the mTPI-2 parameters, results of the niraparib PK 
assessment in Cohort B will be taken into consideration when determining the RP2D for 
TfOS. 
If the PK exposure for the niraparib TfOS in Cohort B is consistent with the exposures 
observed in adults, the niraparib dose in Cohort B will be the basis of determining the 
RP2D for the TfOS. 
Cohort C 
If Cohort A is not cleared based on the mTPI-2 parameters described above, Cohort C 
will be opened using a reduced niraparib dose, determined based on the niraparib PK 
evaluation in Cohort A. The dose of dostarlimab will be the same as in Cohort A.  
If Cohort C is deemed safe based on the mTPI-2 parameters described above, results of 
the niraparib PK assessment in Cohort C will be taken into consideration when 
determining the RP2D for TfOS.  
If the PK exposure for the niraparib TfOS in Cohort C is consistent with the exposures 
observed in adults, the niraparib dose in Cohort C will be the basis of determining the 
RP2D for the TfOS.  
Cohort D 
If the exposures of dostarlimab observed in Cohorts A and B (or Cohorts A and C) are 
substantially lower than those observed in adults, a dose escalation cohort (Cohort D) will 
be opened. The dose of dostarlimab for Cohort D will be determined based on the 
dostarlimab PK evaluation in Cohorts A and B (or Cohorts A and C). A dose of 
 may be tested. The dose level of 
niraparib in Cohort D will be the niraparib RP2D as determined from evaluation in 
Cohorts A, B, and/or C. 
If Cohort D is deemed safe based on the mTPI-2 parameters described above, the dose 
level of dostarlimab from Cohort D will be the RP2D in combination with the niraparib 
RP2D. If Cohort D is not cleared, then the dose level of 
 from Cohort 
 
 will be the RP2D in combination with the niraparib 
RP2D. 
If Cohort C is not deemed safe, the study will not continue as designed. 
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 65 of 213 
Alternate niraparib schedules may be implemented for niraparib, if appropriate. 
Additional dose levels of niraparib and/or dostarlimab may be evaluated based on safety 
and PK data from the specific cohorts. 
 
 
 
Once the RP2D for the combination of the 
 is determined 
in Part 1B of the study, participants <8 years of age will be eligible for enrolment into the 
Part 2 disease-specific expansion cohorts (described in cohort-specific supplements to 
this protocol).  
In addition, once the RP2D is determined, the RP2D cohort in Part 1B will remain open 
until completion of Part 2 overall for additional enrolment to reach minimum N=3 
participants enrolled in Part 1B RP2D within each age category: ≥6 months to <2 years; 
≥2 years to <6 years; ≥6 years to <8 years.  
4.2. 
Intra-Participant Dose Escalation 
For participants who participate in Part 1A and 1B of the study, intra-participant dose 
escalation to a higher dose level of niraparib and/or dostarlimab that has been found to be 
safe during dose escalation may be allowed after all of the following have taken place: 
a. participant has received at least 2 cycles of treatment in their current cohort 
b. participant has required no dose modifications due to AEs 
c. participant has no evidence of progressive disease (PD) 
d. Investigator has determined that dose escalation would be in the best interest of the 
participant 
Such cases must be discussed with the Sponsor. 
4.3. 
Dose Limiting Toxicity 
The DLT observation period is 42 days following the initiation of study treatment (ie, 
approximately the first 2 treatment cycles) in Part 1.  
A participant will be considered unevaluable for DLT assessment if, for reasons other 
than DLT, the participant does not complete the DLT observation period or receives 
<80% of the intended niraparib dose (e.g., missed 9 or more doses; reason for missed 
doses may include, but is not limited to, noncompliance) or <2 infusions of dostarlimab.  
Participants considered unevaluable may be replaced after consultation between the 
Sponsor and Investigator.  
A participant may continue on study treatment following a DLT if the Investigator 
determines doing so is in the best interest of the participant, after discussion by the 
Investigator with the GSK Medical Monitor, and after appropriate recovery from the 
DLT by the participant. 
DLT is defined as any of the following occurring during the first 42 days of study 
treatment: 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 66 of 213 
• 
any treatment-related Grade 4 nonhaematologic clinical (nonlaboratory) AE. 
• 
any treatment-related Grade 3 nonhaematologic clinical (nonlaboratory) AE not 
resolving to Grade ≤1 within 48 hours of initiating optimal medical intervention. 
• 
any treatment-related Grade 3 or 4 nonhaematologic laboratory abnormality if any 
of the following also occur:  
− the abnormality leads to hospitalisation. 
− the abnormality persists for ≥7 days from the time of AE onset and participant 
is symptomatic from the AE and/or requires intervention. 
• 
any treatment-related haematologic toxicity defined as any of the following:  
− Grade 4 thrombocytopenia persists for ≥7 days from the time of AE onset or 
Grade 3 or 4 thrombocytopenia associated with clinically significant bleeding 
or requiring platelet transfusion. 
− Grade 4 neutropenia persists for ≥7 days, Grade 3 or 4 neutropenia associated 
with infection, or Grade 3 or 4 febrile neutropenia persists for ≥72 hours. 
− Grade 4 anaemia or Grade 3 anaemia requiring blood transfusion. 
• 
any treatment-related toxicity leading to prolonged delay (>2 weeks) in initiating 
Cycle 2. 
• 
any treatment-related toxicity resulting in the participant receiving <80% of the 
intended niraparib dose and/or <2 dostarlimab infusions due to dose 
modification/interruption/ reduction. 
• 
any treatment-related Grade ≥2 uveitis, eye pain, or blurred vision that does not 
resolve with topical therapy within 2 weeks. 
• 
any treatment-related Grade ≥2 immune-related endocrine toxicity that requires 
hormone replacement, except Grade 2 thyroiditis or thyroid dysfunction. 
• 
any treatment-related Grade 2 colitis or diarrhoea that persists for ≥7 days without 
resolution to Grade ≤1 despite adequate steroid therapy. 
• 
any Grade 3 or 4 imAE that does not resolve to Grade ≤1 or baseline within 8 days 
despite adequate immune suppressive therapy. 
• 
Grade 3 or higher infusion-related reaction. 
• 
any grade of hemophagocytic lymphohistiocytosis. 
• 
any grade of Posterior Reversible Encephalopathy Syndrome (PRES). 
• 
any treatment-related Grade 5 AE. 
4.4. 
General Study Conduct 
This study consists of a Screening Period (Day -28 to Day -1), a Treatment Period, an 
End of Treatment (EOT) Visit, a Safety Follow-up Visit, and a Follow-up Assessment 
Period. During the Treatment Period, study treatment administration will occur in 3-week 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 67 of 213 
cycles. Participants will receive niraparib daily or on an alternative schedule in 
combination with dostarlimab Q3W until documented PD, unacceptable toxicity, 
withdrawal of consent, Investigator’s decision, or death. 
Participants must have a baseline tumour assessment (computed tomography [CT] or 
magnetic resonance imaging [MRI]) of the chest, abdomen, pelvis, and any additional 
sites as clinically indicated within 28 days prior to the first dose of study treatment. 
Participants with neuroblastoma must also have a baseline tumour assessment via 
metaiodobenzylguanidine-single-photon emission computed tomography/computed 
tomography (MIBG-SPECT/CT) or fluorodeoxyglucose-positron emission 
tomography/computed tomography (FDG-PET/CT) within 42 days prior to the first dose 
of study treatment. A baseline brain scan (IV contrast-enhanced MRI [preferred] or IV 
contrast-enhanced CT) is required for participants with previously treated brain 
metastases. (Participants with previously treated brain metastases may participate under 
the conditions detailed in exclusion criterion 5 in this master protocol and in the 
exclusion criteria of each cohort-specific supplement for Part 2.) 
Tumour assessments by CT or MRI of sites involved by disease at baseline and of any 
additional sites as clinically indicated will be done postbaseline, as will MIBG-
SPECT/CT or FDG-PET/CT tumour assessments (participants with neuroblastoma only). 
Tumour assessments should be conducted every 9 weeks (every 63 [±7] days) for the first 
12 months and then every 12 weeks (every 84 [±7] days) thereafter, following the start of 
study treatment, or more frequently if clinically indicated, until documented PD, the start 
of alternative anticancer treatment, or discontinuation of participant from overall study 
participation (eg, death, participant’s request, loss to follow-up), whichever comes first. 
Tumour assessments should be scheduled using the date of the first dose of study 
treatment as the reference date for all time points and are not to be scheduled based on 
the date of the previous imaging time point. Imaging assessment delay to conform to 
study treatment delay is not permitted.  
Bone scan, whole body MRI, or positron emission tomography (PET) scan will be carried 
out at baseline for all participants in Part 1 (excluding participants with neuroblastoma) 
and in the Part 2 Osteosarcoma Expansion Cohort within 84 days prior to the first dose of 
study treatment to detect bony sites of disease. Subsequent assessments are to be 
performed during the Treatment Period when clinically indicated. If the baseline bone 
scan, whole body MRI, or PET scan is positive for metastatic bone disease, a repeat 
assessment is required for confirmation of partial response (PR) or complete response 
(CR) or if clinically indicated. 
The same imaging technique/modality must be used to follow identified lesions 
throughout the study for a given participant.  
Clinical assessment of superficial lesions should be carried out on the same date as the 
imaging studies or no later than 3 days thereafter and must be recorded in the 
participant’s electronic case report form (eCRF). 
Participants with neuroblastoma will undergo bone marrow assessments at Screening 
and, if positive at baseline, every 9 weeks (every 63 [±7] days) following the start of 
study treatment for the first 12 months and then every 12 weeks (every 84 [±7] days) 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 68 of 213 
thereafter, or more frequently if clinically indicated, until documented PD, the start of 
alternative anticancer treatment, or discontinuation of participant from overall study 
participation (e.g., death, participant’s request, loss to follow-up), whichever comes first. 
Participants who have a PR or CR while on treatment and who discontinue treatment 
prior to the next disease assessment must have all appropriate follow-up disease 
assessments to confirm the observed response no sooner than 4 weeks (28 days) after the 
first observation. 
Blood samples to assess niraparib PK, dostarlimab PK, and dostarlimab antidrug 
antibodies (ADAs) and neutralising antibodies (NAb) will be collected from all 
participants pre- and postdose at the time points specified in Table 3. 
 
 
 Blood samples should be 
collected in order of priority as outlined in Section 8.2. Tumour samples will be collected 
from all participants in Part 2 and also from Part 1 participants, but only under specific 
circumstances such as a treatment response. 
Safety assessments conducted throughout the Treatment Period include symptom-
directed physical examinations, electrocardiograms (ECGs), vital signs, and clinical 
laboratory assessments, including complete blood count (CBC) with differential, 
coagulation profile, chemistry, thyroid function panel, and pregnancy (irrespective of 
prior medical treatment) testing. Psychological assessments will be administered as per 
local standard of care. 
 
 
 
 
All participants will undergo an EOT Visit conducted no more than 7 days following the 
decision to discontinue study treatment and a Safety Follow-up Visit 30 (+7) days after 
the last date of study treatment administration. Participants are expected to complete the 
Safety Follow-up Visit regardless of reason for study treatment discontinuation and even 
if they have started alternative anticancer therapy. During the long-term Follow-up 
Assessment Period, participants will be followed via clinic visit or telephone contact (if 
an in-person visit is not possible) every 90 (±14) days after the last dose of study 
treatment for the first year, every 180 (±14) days for the subsequent 2 years, and yearly 
(±14 days) for an additional 2 years (5 years total), or until the start of alternative 
anticancer therapy (unless there is an ongoing AE/SAE that must be followed until 
resolved, stabilised, or otherwise explained), or until the participant withdraws from the 
study overall, is lost to follow-up, or dies (whichever occurs earlier). 
Collection and recording of all AEs for each participant will start on the day of informed 
consent/assent. Nonserious AEs will be collected until 30 days after the last dose of study 
treatment. Serious adverse events (SAEs) will be collected until 90 days after the last 
dose of study treatment (or to a minimum of 30 days after the last dose of study treatment 
if the participant starts alternative anticancer treatment). However, any SAEs assessed as 
related to study participation or related to study treatment will be collected through the 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 69 of 213 
Follow-up Assessment Period. Adverse events of special interest (AESIs) are defined in 
Appendix 2; AESIs will be collected through the Follow-up Assessment Period as 
described in Section 8.3.6. Details of all pregnancies in female participants and, if 
indicated, female partners of male participants who receive study treatment will be 
collected until 180 days after the last dose of study treatment in female participants and 
90 days after the last dose of study treatment for female partners of male participants. In 
addition, all ongoing AEs and SAEs are to be followed, regardless of start of alternative 
anticancer therapy, until the event is resolved, stabilised, or otherwise explained; until the 
participant has withdrawn consent from the study overall, is lost to follow-up (as defined 
in Section 7.4); or has died. 
4.5. 
Number of Participants 
Under Protocol Amendment 03, approximately 56 participants were planned to be 
enrolled in Part 1 of the study, including approximately 32 participants in Part 1A and 
approximately 24 participants in Part 1B (unless the incidence of DLTs dictated fewer 
participants as per the Dose Escalation Plan described in Section 4.1). See Section 9.1 for 
sample size considerations per cohort. 
A total of 23 participants were enrolled into Part 1A Cohorts 0, 1A, and 1B. Part 1A 
Cohort 1B was not deemed to be safe, and, as a result, no participants were enrolled into 
Part 1A Cohort 2. In addition, a total of 3 participants were enrolled into Part 1B Cohort 
1, for which enrolment into Part 1B Cohort 1 was prematurely stopped due to DLTs of 
Grade ≥3 thrombocytopenia.  
Under Protocol Amendment 05, it is anticipated that, 1 to 3 cohorts (8 participants per 
cohort or approximately 24 participants overall) may be enrolled in Part 1B, unless the 
incidence of DLTs dictates fewer participants as noted in Section 4.1. Additional cohorts 
(including up to 8 participants per cohort) may be opened in Part 1B if needed to evaluate 
alternative niraparib dose levels. Lastly, up to 5 additional participants may be enrolled 
into Part 1B to further evaluate the youngest participant group(s) if not represented.  
Numbers of participants for the Part 2 Osteosarcoma and Neuroblastoma Expansion 
Cohorts are discussed in the relevant protocol supplement.  
4.6. 
Treatment Assignment 
All participants in this single-arm study will receive treatment with niraparib in 
combination with dostarlimab. 
 
 
  
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 70 of 213 
4.7. 
Dose Adjustment Criteria 
4.7.1. 
Niraparib Dose Adjustment for Age and Weight 
When a participant who is <8 years of age experiences a birthday while on study, a 
niraparib dose increase should be considered from the start of their next cycle i.e., Week 
1 (Table 7). For example, if a 6-year-old participant receiving niraparib has a birthday 
and turns 7 years old, then that participant will receive a higher dose of niraparib as 
indicated in Table 7.  
When a participant ≥8 years of age experiences a weight change while on study that 
moves them into a higher or lower weight dosing category in Table 7, a niraparib dose 
adjustment should be considered from the start of the next cycle; i.e., Week 1 of the 
following cycle. 
If a 7-year-old participant has a birthday and turns 8-years-old while on study, then that 
participant will shift to the 
 
 
 
 
 
 
 
 
Niraparib dose may not be adjusted in response to age increase or weight change during 
the first 2 cycles of therapy.  
Following a dose change (increase or decrease), additional niraparib PK samples will be 
obtained (see Table 3, footnote x).  
Following a niraparib dose increase, participants will be closely monitored (Table 3) for 
risk of haematological toxicities as follows:  
• 
Part 1B and Part 2 Safety Run-in: Twice weekly CBC for the period of 2 cycles 
following the increase in niraparib dose.  
• 
Part 2 Expansion Cohorts: Once weekly CBC for the period of 2 cycles 
following the increase in niraparib dose.  
4.7.2. 
Dose Adjustment for Adverse Events 
Adverse reactions should be managed with dose reduction, interruption of treatment, or 
dose discontinuation. 
For dostarlimab, interruption is defined as stopping administration before completion of 
the infusion, including both cases in which the infusion is resumed and completed on the 
same day and cases in which administration is not resumed that day. 
Study intervention delay is defined as withholding study intervention administration for 
longer than the regularly scheduled dosing interval. For dostarlimab dosing delays >12 
weeks, or if AEs do not return to baseline or Grade <1 within 12 weeks (see Table 11), 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 71 of 213 
dostarlimab should be permanently discontinued unless the Investigator and Medical 
Monitor agree there is strong evidence supporting continued treatment. 
All dose reductions, treatment delays (including any missed doses) and discontinuations, 
and the reason for such modifications should be recorded in the eCRF. 
It should be noted that required treatment discontinuation of either niraparib or 
dostarlimab will result in study treatment discontinuation of both treatments.  
4.7.2.1. 
Niraparib 
The recommended dose modifications for adverse reactions should be followed as listed 
in Table 9 and Table 10. Following a dose reduction, participants should not 
subsequently have dose re-escalated unless a discussion with the GSK Medical Monitor 
has occurred. Following 2 dose reductions, participants will not be allowed to further 
dose reduce, and study treatment should be discontinued. Study treatment should be 
discontinued for selected AEs that persist beyond 28 days, as noted below. 
Table 9: 
Niraparib Dose Modifications for Nonhaematologic Adverse 
Reactions 
NCI CTCAE Grade ≥3 adverse 
reaction where prophylaxis is not 
considered feasible or adverse reaction 
event persists despite treatment 
• Withhold niraparib for a maximum of 28 days or 
until resolution of adverse reaction. 
• For those adverse reactions that do not resolve 
within 28 days, niraparib should be discontinued. 
Otherwise, discussion with the GSK Medical 
Monitor is required to resume niraparib. 
• Participants may resume niraparib at a lower dose 
after discussion with the GSK Medical Monitor.a 
NCI CTCAE Grade ≥2 adverse 
reaction of PRES 
• 
Discontinue study treatment for participants. 
Abbreviations: TfOS= tablet for oral suspension; CTCAE=Common Terminology Criteria for Adverse 
Events; NCI=National Cancer Institute; PRES=Posterior Reversible Encephalopathy Syndrome. 
There have been rare reports of niraparib-treated patients developing signs and symptoms 
that are consistent with PRES. PRES is a rare neurologic disorder that can present with 
the following signs and symptoms including seizures, headache, altered mental status, 
visual disturbance, or cortical blindness, with or without associated hypertension. A 
diagnosis of PRES requires confirmation by brain imaging, preferably MRI. In patients 
developing PRES, treatment of specific symptoms including control of hypertension is 
recommended, along with discontinuation of niraparib. The safety of reinitiating 
niraparib therapy in patients previously experiencing PRES is not known. 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 72 of 213 
Table 10: 
Niraparib Dose Modifications for Haematologic Adverse Reactions 
Weekly blood draws for CBC will be monitored until the adverse reaction resolves; after 
resuming niraparib, weekly blood draws for CBC will be required for an additional 4 weeks 
(28 days) after the adverse reaction has been resolved to the specified levels, after which 
monitoring at Week 1 of each cycle may resume (Table 3). 
Platelet count 
<100 000/µL 
First occurrence: 
• Withhold niraparib for a maximum of 28 days and monitor 
blood counts weekly until platelet counts return to 
≥100 000/µL. Resume niraparib at the same or lower dose 
• For those adverse reactions that do not resolve within 28 days, 
study treatment should be discontinued. Otherwise, discussion 
with the GSK Medical Monitor is required to resume niraparib. 
• If nadir platelet count was <75 000/µL, niraparib dose should 
be reduced. 
• Participants may resume niraparib at the same or a lower dose 
after discussion with the GSK Medical Monitor.a. 
Second occurrence: 
• Withhold niraparib for a maximum of 28 days and monitor 
blood counts weekly until platelet counts return to 
≥100,000/µL. 
• For those adverse reactions that do not resolve within 28 days, 
study treatment should be discontinued. Otherwise, discussion 
with the GSK Medical Monitor is required to resume niraparib.  
• If nadir platelet count is <75,000/µL, niraparib dose should be 
reduced. 
• Participants may resume niraparib at a lower dose after 
discussion with the GSK Medical Monitor.a. 
Neutrophil <1000/µL or  
Haemoglobin <8 g/dL 
• Withhold niraparib for a maximum of 28 days and monitor 
blood counts weekly until neutrophil counts return to ≥1000 µL 
or haemoglobin returns to ≥8 g/dL. 
• For those adverse reactions that do not resolve within 28 days, 
study treatment should be discontinued. Otherwise, discussion 
with the GSK Medical Monitor is required to resume niraparib. 
• Participants may resume niraparib at a lower dose after 
discussion with the GSK Medical Monitor.a 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 73 of 213 
Haematologic adverse 
reaction requiring 
transfusion 
• For participants with platelet count ≤10 000/μL, platelet 
transfusion should be considered. If there are other risk factors, 
such as co-administration of anticoagulation or antiplatelet 
drugs, consider interrupting these drugs and/or transfusion at a 
higher platelet count. 
• Red blood cell transfusion(s) may be given at the discretion of 
the Investigator. 
• Participants may resume niraparib at a lower dose after 
discussion with the GSK Medical Monitor.a 
MDS/AML 
Any suspected case of MDS/AML reported while a participant is 
receiving treatment or being followed for post-treatment 
assessments must be referred for evaluation to a local 
haematologist to perform bone marrow aspirate and biopsy as per 
local standards of practice. The study site must receive a copy of 
the haematologist’s report of aspirate/biopsy findings, which must 
include a classification according to the WHO, and other sample 
testing reports related to MDS/AML. If a diagnosis of MDS/AML 
is confirmed by a haematologist, the participant must permanently 
discontinue study treatment. 
Abbreviations: TfOS= tablet for oral suspension; CBC=complete blood count. 
For clinical situations not covered by this dose modification guidance, the Investigator 
must contact the GSK Medical Monitor. 
4.7.2.2. 
Dostarlimab 
Given the mechanism of action of dostarlimab, it is anticipated that activation of the 
cellular immune system can be manifested as imAEs. An imAE is defined as an AE of 
any organ that is associated with study intervention exposure, is of unknown etiology, 
and is consistent with an immune-related mechanism. Special attention should be paid to 
AEs that may be suggestive of potential imAEs. Onset of imAEs can occur after the first 
dose, later after several doses have been administered, or several months after the last 
dose of immunotherapy treatment (Ramos-Casals, 2020). 
Early recognition of drug-related imAEs and initiation of treatment are critical in 
mitigating severity and reducing the risk of complications, because the majority of 
imAEs are reversible with the use of steroids and other immune suppressants or therapies 
(Pardoll, 2012; Weber , 2012). If a drug-related imAE is suspected, the participant should 
return to the study site as soon as possible instead of waiting for their next scheduled 
visit. Participants who experience a new or worsening imAE should be contacted and/or 
evaluated at the study site more frequently. A thorough evaluation should be conducted to 
rule out neoplastic, infectious, metabolic, toxin-related, or other etiologies before 
diagnosing a drug-related imAE. Serological, immunological, and histological (i.e., via a 
biopsy) data should be considered to support the diagnosis of an immune-related toxicity. 
Consultation with an appropriate medical specialist should be considered when 
investigating a possible imAE. 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 74 of 213 
For all imAEs of interest (imAEIs) listed in Table 11, dostarlimab should be held until 
participant is clinically and metabolically stable and AEs are resolved to Grade 1 or less. 
If systemic steroids are used as a part of imAEI management, total dose of daily steroids 
should be equal to or less than prednisone 10 mg at the time of resuming dostarlimab. All 
AEs are to be graded according to NCI CTCAE v5 (US Department of Health and 
Human Services, 2017) 
Table 11 includes details on the management of dostarlimab dose delays and 
discontinuation for specific events. Institutional management guidelines, the SITC 
clinical practice guideline on immune checkpoint inhibitor-related AEs (Naidoo, 2023) 
and the NCCN clinical practice guideline for management of imAEs (NCCN, 2021), the 
ESMO clinical practice guideline for management of toxicities from immunotherapy 
(Haanen, 2022) and/or the ASCO guideline on management of immune-related adverse 
events in patients treated with immune checkpoint inhibitor therapy (Brahmer, 2021) 
should be consulted and used to supplement the algorithms provided below. In cases 
where the Investigator is directed to discontinue study intervention permanently, these 
instructions are mandatory; some exceptions may be permitted after consultation with the 
Sponsor if the dose modification/treatment guidelines in Table 11 and/or Table 12 differ 
from the institutional or professional society guidance. The Medical Monitor can be 
contacted if there are additional questions about PD-1 inhibitor-related AE management. 
 

CONFIDENTIAL 
GSK group of companies 
 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 75 of 213 
Table 11: 
Guidelines for Treatment of Immune-mediated Adverse Events 
Toxicity 
Toxicity Grade or 
Conditions (NCI 
CTCAE v5.0) 
Action Taken with 
Dostarlimab 
imAE Management with 
Corticosteroid and/or Other 
Therapies 
Monitoring and Follow-up 
General instructions: This table provides guidelines for dose modifications/dose discontinuations for AEs that are suspected to be imAEs related to the ICI. 
Corticosteroid taper should be initiated upon AE improving to Grade ≤1 and continue to taper over at least 4 weeks. 
For situations where study intervention has been withheld, administration can be resumed after the AE has been reduced to Grade ≤1 and corticosteroid has been tapered. Study 
intervention should be permanently discontinued if the AE does not resolve within 12 weeks of last dose or corticosteroids cannot be reduced to ≤10 mg/day prednisone, or 
equivalent, within 12 weeks. 
For severe and life-threatening imAEs, IV corticosteroid should be initiated first, followed by oral steroid. Other immunosuppressive treatment should be initiated if imAEs cannot be 
controlled by corticosteroids. 
Uveitis 
Grade 2 
Withhold 
Urgent ophthalmology consultation. 
Administer treatment with ophthalmic 
and systemic 
prednisone/methylprednisolone. 
Ensure adequate evaluation (e.g., urgent 
ophthalmology consultation). 
Grade 3 or 4 
Permanently discontinue 
Diarrhoea/colitis 
Grade 2-3 
Withhold dose. Restart dosing 
when toxicity resolves to Grade 
0 to 1. 
Administer corticosteroids (initial dose 
of 1 to 2 mg/kg methylprednisolone or 
equivalent) followed by taper. 
Monitor carefully for signs and symptoms 
of enterocolitis (such as diarrhoea, 
abdominal pain, blood or mucus in stool, 
with or without fever) and of bowel 
perforation (such as peritoneal signs and 
ileus). 
Participants with Grade ≥2 diarrhoea 
where colitis is suspected should 
consider GI consultation and an 
endoscopy to rule out colitis. 
All participants who experience 
diarrhoea/colitis should be advised to 
drink liberal quantities of clear fluids. If 
sufficient oral fluid intake is not feasible, 
Grade 4 
Permanently discontinue  

CONFIDENTIAL 
GSK group of companies 
 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 76 of 213 
Toxicity 
Toxicity Grade or 
Conditions (NCI 
CTCAE v5.0) 
Action Taken with 
Dostarlimab 
imAE Management with 
Corticosteroid and/or Other 
Therapies 
Monitoring and Follow-up 
fluid and electrolytes should be 
substituted via IV infusion.  
AST/ALT elevation, increased 
bilirubin or hepatitis 
Grade 2 with 
AST/ALT >3 and up 
to 5×ULN or  
total bilirubin >1.5 and 
up to 3×ULN 
Withhold dose. Restart dosing 
when toxicity resolves to 
Grade 0 to 1. 
Inform GSK Medical Monitor 
before resuming dose.  
Administer corticosteroids (initial dose 
of 0.5 to 1 mg/kg methylprednisolone or 
equivalent) followed by taper. 
Inform GSK Medical Monitor 
Monitor with liver function tests (consider 
weekly or more frequently until liver 
enzyme value[s] return to baseline or are 
stable). 
Ensure adequate hepatology evaluation 
(e.g., hepatologist consultation) 
See Section 7.1.1, Appendix 8 and 
Appendix 9 for additional details on liver 
event follow-up assessments. 
Grade 3 with AST / 
ALT >5×ULN  
up to 8x ULN 
Discontinue  
See Section for liver chemistry 
stopping criteria and 
monitoring guidance, and for 
liver rechallenge process and 
criteria. 
Administer corticosteroids (1 to 2 mg/kg 
methylprednisone or equivalent), 
followed by taper 
Strongly recommend specialist 
hepatology evaluation 
See Section 7.1.1, Appendix 8 and 
Appendix 9 for liver chemistry monitoring 
guidance 
Grade 3 (AST or ALT 
>8x ULN up to 
20xULN) or total 
bilirubin > 3xULN (up 
to 10xULN) 
Permanently discontinue 
See Section 7.1.1 for liver 
chemistry stopping criteria and 
monitoring guidance 
Administer corticosteroids (initial dose 
of 1 to 2 mg/kg methylprednisolone or 
equivalent) followed by taper. 
Inform GSK Medical Monitor 
See Section 7.1.1 for liver chemistry 
monitoring guidance. 
Strongly recommend specialist 
hepatology evaluation. 
Grade 4 (AST or ALT 
>20x ULN or total 
bilirubin >10x ULN) 
Permanently discontinue 
See Section 7.1.1 for liver 
chemistry stopping criteria and 
monitoring guidance 
Administer corticosteroids (initial dose 
of 2 mg/kg methylprednisolone or 
equivalent) followed by taper. 
Inform GSK Medical Monitor 
See Section 7.1.1 for liver chemistry 
monitoring guidance. 

CONFIDENTIAL 
GSK group of companies 
 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 77 of 213 
Toxicity 
Toxicity Grade or 
Conditions (NCI 
CTCAE v5.0) 
Action Taken with 
Dostarlimab 
imAE Management with 
Corticosteroid and/or Other 
Therapies 
Monitoring and Follow-up 
Specialist hepatology evaluation is 
recommended. 
T1DM or hyperglycaemia 
Grade 3-4 
hyperglycaemia or 
T1DM (associated 
with metabolic 
acidosis or ketonuria) 
Withhold dose.  
Restart dosing in appropriately 
managed, clinically and 
metabolically stable 
participants. Insulin 
replacement therapy is 
required. 
Initiate insulin replacement therapy for 
participants with T1DM. 
Monitor participants for hyperglycaemia 
or other signs and symptoms of diabetes. 
Ensure adequate evaluation (e.g., 
specialist consultation). 
Hypophysitis 
2-4 
Hold until hormonal therapy 
results return to adequate 
levels by laboratory values and 
restart dosing when toxicity 
resolves to Grade 0 to 1.  
For recurrence or worsening of 
Grade ≥2 hypophysitis after 
steroid taper has been 
completed and is on adequate 
hormone replacement therapy, 
permanently discontinue.  
Administer corticosteroids and initiate 
HRT as clinically indicated. 
Monitor for signs and symptoms of 
hypophysitis (including hypopituitarism 
and adrenal insufficiency) 
Ensure adequate endocrine evaluation 
(e.g., endocrine consultation). 

CONFIDENTIAL 
GSK group of companies 
 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 78 of 213 
Toxicity 
Toxicity Grade or 
Conditions (NCI 
CTCAE v5.0) 
Action Taken with 
Dostarlimab 
imAE Management with 
Corticosteroid and/or Other 
Therapies 
Monitoring and Follow-up 
Adrenal insufficiency 
2-4 
Hold until hormonal therapy 
results in return to adequate 
levels by laboratory values and 
restart dosing when toxicity 
resolves to Grade 0 to1.  
For recurrent or worsening 
Grade ≥2 adrenal insufficiency 
while adequate hormonal 
replacement is continuing, 
permanently discontinue 
Start treatment with corticosteroids 
before other HRT to avoid adrenal crisis 
(hydrocortisone slowly titrating doses 
down according to symptoms or 
prednisone and fludrocortisone titrating 
up or down based on BP, other 
symptoms, and laboratory results); 
participants with severe symptoms may 
require additional fluids (e.g., saline 
>2L). 
Monitor for cortisol level (AM), 
comprehensive metabolic panel (Na, K, 
CO2, and glucose), and renin. 
Ensure adequate endocrine evaluation 
(e.g., endocrine consultation). 
Hyperthyroidism  
3 or 4 
Hold until hormonal therapy 
results in return to adequate 
levels by laboratory values and 
restart dosing when toxicity 
resolves to Grade 0 to 1. 
Treat with nonselective beta-blockers 
(e.g., propranolol) or thionamides as 
appropriate.  
Monitor for signs and symptoms of 
thyroid disorders 
Ensure adequate evaluation (e.g., 
endocrine consultation). 
Hypothyroidism 
3 or 4 
Hold until administration of 
HRT results in return to 
adequate hormone levels 
based on laboratory values 
and restart dosing when 
toxicity resolves to Grade 0 to 
1 
Initiate thyroid replacement hormones 
(e.g., levothyroxine or liothyronine) per 
standard of care. 
Monitor for signs and symptoms of 
thyroid disorders. 
Monitor thyroid function tests. 
Ensure adequate evaluation (e.g., 
endocrine consultation). 
Exclude concomitant adrenal 
insufficiency (AM cortisol level). 

CONFIDENTIAL 
GSK group of companies 
 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 79 of 213 
Toxicity 
Toxicity Grade or 
Conditions (NCI 
CTCAE v5.0) 
Action Taken with 
Dostarlimab 
imAE Management with 
Corticosteroid and/or Other 
Therapies 
Monitoring and Follow-up 
Pneumonitis 
2 
Withhold dose. Restart dosing 
when toxicity resolves to 
Grade 0 to 1.  
Administer corticosteroids (eg, 1 to 
2 mg/kg/day of prednisone or 
equivalent)  
Taper corticosteroids when symptoms 
improve to Grade 1 or less over no less 
than 4 weeks (28 days).  
Monitor participants for signs and 
symptoms of pneumonitis. 
Evaluate participants with suspected 
pneumonitis with radiological imaging 
and initiate corticosteroid treatment. 
Ensure adequate evaluation (e.g., 
specialist pulmonologist / respiratory 
opinion) 
Add prophylactic antibiotics for 
opportunistic infections (e.g., PJP). 
3-4 or recurrent 
Grade 2 
Permanently discontinue 
IV for Grade 3 to 4 (eg, 1 to 2 
mg/kg/day of prednisone or equivalent).  
Taper corticosteroids when symptoms 
improve to Grade 1 or less over no less 
than 4 weeks (28 days). 
Exfoliative dermatologic 
conditions 
Suspected SJS, TEN, 
or DRESS 
Withhold if suspected 
Treat with high potency topical steroids 
to affected areas. 
Treat with prednisone. 
Ensure adequate evaluation (e.g., urgent 
dermatology consultation) to confirm 
etiology and exclude other causes. 
Confirmed SJS, TEN, 
or DRESS 
Permanently discontinue 
Administer 1 to 2 mg/kg/day IV 
methylprednisolone and taper steroid 
when dermatitis is controlled. 

CONFIDENTIAL 
GSK group of companies 
 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 80 of 213 
Toxicity 
Toxicity Grade or 
Conditions (NCI 
CTCAE v5.0) 
Action Taken with 
Dostarlimab 
imAE Management with 
Corticosteroid and/or Other 
Therapies 
Monitoring and Follow-up 
Renal failure or nephritis 
2 
Withhold dose. Restart dosing 
when toxicity resolves to Grade 
0 to 1. 
Oral for Grade 2 (initial dose of 0.5 to 
1 mg/kg/day of prednisone or 
equivalent) 
Taper corticosteroids when symptoms 
improve to Grade 1 or less over no less 
than 4 weeks (28 days). 
Monitor participants for signs and 
symptoms, including monitoring of 
creatinine and urine protein every 3 to 7 
days. 
Ensure adequate evaluation (e.g., 
nephrology consultation, renal biopsy) to 
confirm etiology and exclude other 
causes. 
Consider inpatient care for Grade 3 to 4. 
3-4 
Permanently discontinue. 
IV for Grade 3 to 4 (1 to 2 mg/kg/day of 
prednisone or equivalent). 
Consider adding 1 of the following after 
1 week of steroids: azathioprine, 
cyclosporine, cyclophosphamide, 
infliximab, mycophenolate. 
If persistent Grade 2 beyond 1 week, 
prednisone/ methylprednisolone. 
Taper corticosteroids when symptoms 
improve to Grade 1 or less over no less 
than 4 weeks (28 days). 
Myositis 
2-3 
Restart dosing when toxicity 
resolves to Grade 0 to 1. 
Oral for Grade 2 (initial dose of 0.5 to 
1 mg/kg/day of prednisone or 
equivalent) 
IV for Grade 3 to 4 (1 to 2 mg/kg/day of 
prednisone or equivalent). 
Taper corticosteroids when symptoms 
improve to Grade 1 or less over no less 
than 4 weeks (28 days). 
Ensure adequate evaluation.  
4 
Permanently discontinue. 

CONFIDENTIAL 
GSK group of companies 
 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 81 of 213 
Toxicity 
Toxicity Grade or 
Conditions (NCI 
CTCAE v5.0) 
Action Taken with 
Dostarlimab 
imAE Management with 
Corticosteroid and/or Other 
Therapies 
Monitoring and Follow-up 
Myocarditis 
Any grade 
Permanently discontinue. 
Administer high-dose corticosteroids 
(1 g/day of IV methylprednisolone) for 3 
to 5 days. If responding and stable, 
switch to oral prednisone taper over 6 to 
12 weeks based on clinical response 
and improvement in cardiac biomarkers. 
If no improvement in 24 to 48 hours, 
consider adding other potent 
immunosuppressive agents. 
Ensure adequate evaluation (e.g., urgent 
cardiology consultation) to confirm 
etiology and/or exclude other causes. 
Severe neurological events 
(myasthenic 
syndrome/myasthenia gravis, 
Guillain-Barré syndrome, 
transverse myelitis) 
Grade 2, 3, or 4 
Permanently discontinue 
Consider high dose corticosteroids and 
other therapies as needed. 
It is highly recommended that 
Investigators discuss any AEs with the 
Sponsor before using infliximab. 
Ensure adequate evaluation (e.g., 
neurology consultation). 
Consider MRI of brain and/or spine 
depending on symptoms. 
Consider inpatient management as 
clinically indicated. 
Encephalitis 
Any grade 
Permanently discontinue 
Consider IV acyclovir until PCR results 
obtained. 
Trial with methylprednisolone; if severe, 
treatment with methylprednisolone. 
If positive for autoimmune 
encephalopathy antibody or no 
improvement after 7 to 14 days, 
consider rituximab. 
Ensure adequate evaluation to confirm 
etiology and/or exclude other causes. 
Obtain specialist neurology consultation. 

CONFIDENTIAL 
GSK group of companies 
 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 82 of 213 
Toxicity 
Toxicity Grade or 
Conditions (NCI 
CTCAE v5.0) 
Action Taken with 
Dostarlimab 
imAE Management with 
Corticosteroid and/or Other 
Therapies 
Monitoring and Follow-up 
Other imAEs 
Based on severity 
and type of reaction 
(Grade 2 or 3) 
Withhold. Restart dosing when 
toxicity resolves to Grade 0 or 
1.  
Based on severity of AE, administer 
corticosteroids. When controlled, taper 
steroid. 
Ensure adequate evaluation (including 
specialist consultation) to confirm 
etiology and exclude other causes. 
Grade 4 or recurrent 
Grade 3 
Permanently discontinue. 
Recurrence of imAE in this table 
after resolution to Grade ≤1 
Grade 1 or 2 
Withhold (except for 
pneumonitis, see above). 
Based on severity of AEs, administer 
appropriate treatment until symptoms 
improve to Grade ≤2. 
Ensure adequate evaluation (e.g. 
specialist opinion). 
3-4 
Permanently discontinue. 
Hemophagocytic 
lymphohistiocytosis (HLH) 
Suspected HLH 
Withhold  
Obtain specialist opinion for diagnosis 
and management. 
Obtain specialist opinion for monitoring 
and follow-up. 
Confirmed HLH 
Permanently discontinue 
Obtain specialist opinion for 
management. 
Abbreviations: ALT=alanine aminotransferase; AST=aspartate aminotransferase; CTCAE=Common Terminology Criteria for Adverse Events; GI=gastrointestinal; HRT=hormone 
replacement therapy; ICI=immune checkpoint inhibitor; imAE=immune-mediated adverse event; imAEI=immune-mediated adverse event of interest; PCR=polymerase chain 
reaction; T1DM=type 1 diabetes mellitus; ULN=upper limit of normal; SJS=Stevens-Johnson syndrome; TEN= toxic epidermal necrolysis; DRESS=Drug Rash with Eosinophilia 
and Systemic Symptoms. 
 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 83 of 213 
Participants receiving IV study treatment may develop signs and symptoms of an infusion 
reaction during or shortly after drug infusion. These reactions generally resolve 
completely within 24 hours of completion of infusion. Table 12 shows treatment 
guidelines for participants who experience infusion-related reactions associated with 
administration of study treatment, including actions to be taken with the study treatment, 
if necessary. 
 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 84 of 213 
Table 12: 
Infusion Reaction Treatment Guidelines 
NCI-CTCAE Grade 
Treatment 
Premedication at Subsequent 
Dosing 
Grade 1 
Mild reaction; infusion interruption not indicated; treatment 
not indicated 
Increase monitoring of vital signs as medically indicated 
until the participant is deemed medically stable in the 
opinion of the Investigator. 
None 
Grade 2 
Requires infusion interruption but responds promptly to 
symptomatic treatment (eg, antihistamines, NSAIDs, 
narcotics, or IV fluids); prophylactic medications indicated 
for ≤24 hours 
Stop infusion and monitor symptoms. 
Additional appropriate medical therapy may include, but is 
not limited to the following:  
• IV fluids 
• Antihistamines 
• NSAIDs 
• Acetaminophen 
• Narcotics 
Increase monitoring of vital signs as medically indicated 
until the participant is deemed medically stable in the 
opinion of the Investigator. 
If symptoms resolve within 1 hour of stopping drug infusion, 
the infusion may be restarted at 50% of the original infusion 
rate (eg, from 100 mL/h to 50 mL/h). Otherwise, dosing will 
be withheld until symptoms resolve, and the participant 
should be premedicated for the next scheduled dose. 
Participants who develop Grade 2 toxicity despite 
adequate premedication should be permanently 
discontinued from further study treatment 
administration. 
Participant may be premedicated 
1.5 hours (± 30 minutes) prior to 
infusion of dostarlimab with the 
following:  
• Diphenhydramine 50 mg PO 
(or equivalent dose of 
antihistamine) 
• Acetaminophen 500 to 
1000 mg PO (or equivalent 
dose of antipyretic) 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
 
Page 85 of 213 
NCI-CTCAE Grade 
Treatment 
Premedication at Subsequent 
Dosing 
Grade 3: 
Prolonged (ie, not rapidly responsive to symptomatic 
medication and/or brief interruption of infusion); recurrence 
of symptoms following initial improvement; hospitalisation 
indicated for other clinical sequelae (eg, renal impairment, 
pulmonary infiltrates) 
Grade 4: 
Life-threatening; pressor or ventilatory support indicated 
Stop Infusion. 
Additional appropriate medical therapy may include, but is 
not limited to the following:  
• IV fluids 
• Antihistamines 
• NSAIDs 
• Acetaminophen 
• Narcotics 
• Oxygen 
• Pressors 
• Corticosteroids 
• Epinephrine 
Increase monitoring of vital signs as medically indicated 
until the participant is deemed medically stable in the 
opinion of the Investigator. 
Hospitalisation may be indicated. 
Participant is permanently discontinued from further 
study treatment administration. 
No subsequent dosing. 
Abbreviations: IV=intravenous; NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events; NSAID=nonsteroidal anti-inflammatory 
drug; PO=orally. 
Note: Appropriate resuscitation equipment should be available in the room and a physician is readily available during the period of study treatment administration. 
 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 86 of 213 
4.8. 
End of Study Definition 
The end of the study is defined as the date of completion of the last visit of the last 
participant in the study or the date of completion of the last scheduled procedure shown 
in the applicable SoA for the last participant in any part of the study globally.  
A participant is considered to have completed the study if the participant has completed 
all study assessments, including the last scheduled procedure shown in Table 3 for Part 1 
and in the SoAs specific to the cohorts provided in the supplements.  
4.9. 
Study Conduct 
4.9.1. 
Procedures by Visit 
Standard of care tests/procedures, including laboratory assessments, ECG, physical 
examination, vital signs, height, weight, and performance status, performed before the 
enrolment into the study can be used as part of the screening assessments as long as the 
tests/procedures are performed within this visit window indicated in Table 3. Local 
laboratory assessments (chemistry, coagulation, and haematology) must be performed, 
and results reviewed within 7 days prior to administration of the first dose of study 
treatment, as indicated in Table 3. Tumour assessment (CT or MRI), MIBG-SPECT/CT 
or FDG-PET/CT scan (participants with neuroblastoma only), and bone scan, whole body 
MRI, or PET scan (Part 1 [excluding participants with neuroblastoma] and Part 2 
Osteosarcoma Expansion Cohort) obtained per the standard of care prior to the first dose 
of study treatment (within 28 days for CT or MRI, 42 days for MIBG-SPECT/CT or 
FDG-PET/CT, and 84 days for bone scan, whole body MRI, or PET scan) do not need to 
be repeated and are acceptable to use as baseline evaluations if the conditions presented 
in Section 8.1.2.1 are met. Source documents must clearly identify the standard of care 
tests/procedures that are used for Screening, and the results of these tests/procedures must 
be entered in the eCRF. Table 3 details which procedures are performed at each visit. 
4.9.2. 
General Guidance for Treatment Continuity when Participants are 
Unable to Come into the Clinic 
Due to the significant challenges that currently face the healthcare system and 
participants due to Coronavirus Disease 2019 (COVID-19), as well as the potential for 
enduring or additional quarantine measures, the following guidance is being provided in 
this protocol. In the spirit of global diversity in the COVID-19 pandemic and its impact 
on healthcare in each individual country as well as the recently issued guidance by 
several regulatory authorities, the autonomy of each investigative site to assess the 
benefit/risk for their participants participating in clinical studies should be maintained. 
Prior to utilisation of any of the measures outlined in this section, discussion and 
approval must be obtained from Sponsor/contract research organisation. 
It is expected that sites participating in clinical studies will make every effort to ensure 
proper monitoring and well-being of enrolled participants by adhering to safety 
monitoring as outlined in the SoA (Table 3). The use of local laboratories and local 
radiology centres to reduce the need for a participant to come into the clinic are 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 87 of 213 
supported, if deemed necessary for the well-being of the participant. These local facilities 
should be added to regulatory documents, as required. 
Additionally, regulatory guidance issued in response to the COVID-19 pandemic 
supports the use of central and remote monitoring programs to maintain oversight of 
clinical sites. Any restrictions in place at the site that will impact monitoring and/or 
participant access to the site and care providers should be communicated to the 
Sponsor/contract research organisation. 
General rules for participants with limited possibility to travel are as follows: 
• 
If possible, replace in-person visits with phone contact or alternative location for 
assessment (eg, local laboratories and imaging centres). 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 88 of 213 
5. 
STUDY POPULATION  
Prospective approval of protocol deviations to recruitment and enrolment criteria, also 
known as protocol waivers or exemptions, are not permitted. 
5.1. 
Participant Inclusion Criteria 
Participant will be eligible for Part 1 of the study if all of the following criteria are met: 
2. Participant is child or adolescent ≥6 months to <18 years old at the time of informed 
consent/assent. If a participant is enrolled under Protocol Amendment 05, the 
participant must be ≥6 months to <8 years old at the time of informed consent/assent. 
3. Participant with disease other than neuroblastoma has radiologically measurable 
disease at screening that can be tracked as RECIST v1.1 target lesion(s) . 
Participant with neuroblastoma has measurable/evaluable target and/or non-target 
disease by International Neuroblastoma Response Criteria (INRC) at screening. 
Neuroblastoma participants with recurrent/relapsed bone metastasis that is MIBG-
positive (or FDG-positive, for MIBG-nonavid tumours) as only site of disease are 
eligible. 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 89 of 213 
5. Performance status must be ≥60% on the Karnofsky scale for participants >16 years 
of age and ≥60% on the Lansky scale for participants ≤16 years of age. 
Note: Neurologic deficits in participants with brain metastases must have been stable 
for at least 7 days prior to study enrolment. Participants who are unable to walk 
because of paralysis, but who are upright in a wheelchair, will be considered 
ambulatory for the purpose of assessing the performance status. 
6. Participant has adequate organ function, defined as follows:  
Note: The participant must not have received blood transfusion, growth factors, or 
platelet stimulating agents in the 14 days prior to providing a sample for 
haematologic analysis nor erythropoietin in the prior 6 weeks. 
a. absolute neutrophil count (ANC) ≥1000/μL 
b. platelets ≥100 000/μL 
c. haemoglobin ≥8 g/dL or ≥5.0 mmol/L 
d.  serum creatinine≤1.5×upper limit of normal (ULN) for age or calculated 
creatinine clearance or radioisotope glomerular filtration rate 
≥60 mL/min/1.73m2 
e. total bilirubin ≤1.5×ULN or direct bilirubin ≤1×ULN 
f. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 
≤2.5×ULN unless liver metastases are present, in which case AST and ALT must 
be ≤5×ULN 
g. international normalised ratio or prothrombin time (PT) ≤1.5×ULN unless the 
participant is receiving anticoagulant therapy, as long as PT or partial 
thromboplastin time (PTT) is within therapeutic range of intended use of 
anticoagulants 
h. activated PTT ≤1.5×ULN unless the participant is receiving anticoagulant 
therapy as long as PT or PTT is within therapeutic range of intended use of 
anticoagulants 
7. A female participant is eligible to participate if she is not pregnant or breastfeeding 
and at least one of the following conditions applies:  
a. Is not a woman of childbearing potential (WOCBP). 
or 
b. 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 3, from the Screening Visit through at least 180 days after the last 
dose of study treatment and agrees not to donate eggs (ova, oocytes) for the 
purpose of reproduction during this period. The Investigator should evaluate the 
effectiveness of the contraceptive method in relationship to the first dose of study 
treatment. 
c. A WOCBP must have a negative highly sensitive pregnancy test (urine or serum, 
as required by local regulations) within 24 hours prior to the first dose of study 
treatment and irrespective of prior medical treatment. 
Additional requirements for pregnancy testing during and after the Treatment Period 
are located in Section 8.2.9. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 90 of 213 
The Investigator is responsible for review of medical history, menstrual history, and 
recent sexual activity to decrease the risk for inclusion of a woman with an early 
undetected pregnancy. 
8. A male participant of reproductive potential is eligible to participate if he agrees to 
the following starting with the first dose of study treatment through at least 90 days (a 
spermatogenesis cycle) after the last dose of study treatment: 
a. refrain from donating sperm 
plus, either: 
b. be abstinent from heterosexual intercourse as their preferred and usual lifestyle 
(abstinent on a long-term and persistent basis) and agree to remain abstinent 
or 
c. must agree to use a male condom and should also be advised of the benefit for a 
female partner to use a highly effective method of contraception, as a condom 
may break or leak, when having sexual intercourse with a WOCBP who is not 
currently pregnant 
9. The Investigator, or a person designated by the Investigator, will obtain written 
informed consent from each study participant or the participant’s legally acceptable 
representative, parent(s), or legal guardian and the participant’s assent, when 
applicable, before any study-specific activity is performed. The Investigator will 
retain the original copy of each participant’s signed consent/assent document. 
Inclusion criteria for Part 2 of the study are described in each cohort-specific supplement. 
5.2. 
Participant Exclusion Criteria 
Participant will not be eligible for study entry if any of the following criteria are met: 
1. Participation presents unacceptable risk to the prospective participant based on the 
Investigator’s judgment. 
2. Participant has known hypersensitivity to dostarlimab or niraparib, their components, 
or their excipients. 
3. Participant has a known history of myelodysplastic syndrome (MDS) or AML. 
4. Participant has active autoimmune disease that has required systemic treatment in the 
past 2 years (i.e., with use of disease-modifying antirheumatic drugs, corticosteroids, 
or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or 
physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) 
is not considered a form of systemic treatment.  
5. Participant has known active CNS metastases, carcinomatous meningitis, or both. 
Note: Participants with previously treated brain metastases may participate provided 
they are clinically stable and have no evidence of new, enlarging, or progressing brain 
metastases (using the identical imaging modality for each assessment, either MRI or 
CT scan) for at least 4 weeks (28 days) prior to the first dose of study treatment. In 
addition, the participant must have not been using steroids for at least 7 days prior to 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 91 of 213 
the first dose of study treatment. Carcinomatous meningitis precludes a participant 
from study participation regardless of clinical stability. 
6. Participant had a known (second primary) additional malignancy that progressed or 
required active treatment within the last 2 years. 
7. Participant is considered a poor medical risk due to a serious, uncontrolled medical 
disorder, nonmalignant systemic disease, or active infection that requires systemic 
therapy. Specific examples include, but are not limited to, history of (noninfectious) 
pneumonitis that required steroids or current pneumonitis, uncontrolled ventricular 
arrhythmia, uncontrolled major seizure disorder, unstable spinal cord compression, 
superior vena cava syndrome, or any psychiatric or substance abuse disorders that 
would interfere with cooperation with the requirements of the study (including 
obtaining assent/consent).  
8. Participant has a condition (such as transfusion-dependent anaemia or 
thrombocytopenia), requirement for therapy, or laboratory abnormality that might 
confound the study results or interfere with the participant’s participation for the full 
duration of the study treatment. 
9. Participant is pregnant, breastfeeding, or expecting to conceive within the projected 
duration of the study, starting with the Screening Visit through 180 days after the last 
dose of study treatment.  
No data are available regarding the presence of dostarlimab or niraparib or its 
metabolites in human milk, or on its effects on the breastfed infant or milk 
production. Because of the potential for serious adverse reactions in breastfed infants 
from dostarlimab and/or niraparib, female participants should not breastfeed during 
treatment with dostarlimab and/or niraparib and for at least 4 months after the last 
dose of dostarlimab or at least 30 days after the last dose of niraparib, whichever is 
longer. 
10. Participant has a diagnosis of immunodeficiency or is receiving systemic steroid 
therapy or any other form of immunosuppressive therapy within 7 days prior to the 
first dose of study treatment. 
11. Participant has a known history of HIV (type 1 or 2 antibodies). 
12. Participant has documented presence of HbsAg and/or HBcAb at Screening or within 
3 months prior to first dose of study intervention. Participants with a negative HbsAg 
and positive HbcAb result are eligible only if HBV DNA is negative (Appendix 12) 
13. Participant must not have a gastrointestinal condition, such as bowel obstruction, that 
can impact absorption of oral medications and is identified by clinical symptoms or 
CT scan, etc. 
14. Participant has had any known Grade 3 or 4 anaemia, neutropenia, and/or 
thrombocytopenia that was related to the most recent prior anticancer treatment and 
that persisted >4 weeks (28 days). 
15. Participant has not recovered (i.e., to Grade ≤1 or to baseline) from prior systemic 
anticancer therapy-induced AEs. Note: Participants with alopecia, hearing 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 92 of 213 
impairment, Grade ≤2 neuropathy, Grade ≤2 fatigue, Grade ≤ 2 anaemia, and/or 
Grade ≤2 neutropenia are an exception to this criterion and may qualify for 
participation in the study. 
16. Participant had toxicity related to prior immunotherapy that led to treatment 
discontinuation. 
17. Participant had treatment with systemic anticancer therapy (investigational agent or 
device, or approved chemotherapy, targeted therapy, immunotherapy, or other 
systemic therapy) within 3 weeks or 5 half-lives, whichever is shorter, prior to the 
first dose of study treatment; radiation therapy encompassing >20% of the bone 
marrow within 2 weeks prior to the first dose of study treatment; or any radiation 
therapy within 1 week prior to the first dose of study treatment. 
18. Participant has not recovered adequately from AEs or complications from any major 
surgery prior to starting study treatment. 
19. Participant has received a live vaccine within 30 days of planned start of study 
treatment. 
20. Participant has clinically significant cardiovascular disease (eg, significant cardiac 
conduction abnormalities, uncontrolled hypertension, cardiac arrhythmia or unstable 
angina, New York Heart Association Grade 2 or greater congestive heart failure, 
serious cardiac arrhythmia requiring medication, and history of cerebrovascular 
accident) within 6 months of enrolment. 
21. Participant has heart rate-corrected QT interval prolongation at screening >450 msec 
or >480 msec for participants with bundle branch block.  
Notes: 
• 
The QTc is the QT interval corrected for heart rate according to Bazett’s 
formula (QTcB), Fridericia’s formula (QTcF), and/or another method, 
machine read or manually over read. 
• 
The specific formula that will be used to determine eligibility and 
discontinuation for an individual participant must be determined prior to 
initiation of the study and used consistently for eligibility and study 
assessments.  
22. Participant has received a solid organ transplant. 
23. Participant has a documented presence of HCV antibody at Screening or within 3 
months prior to first dose of study intervention. NOTE: Participants with a positive 
HCV antibody test result due to prior resolved disease can be enrolled, if a 
confirmatory HCV RNA test is negative and the participant otherwise meets entry 
criteria. 
24. Participant has a documented presence of HCV RNA at Screening or within 3 months 
prior to first dose of study intervention. NOTE: The HCV RNA test is optional and 
participants with negative HCV antibody test are not required to undergo HCV RNA 
testing as well. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 93 of 213 
Exclusion criteria for Part 2 of the study are described in each cohort-specific 
supplement. 
5.3. 
Lifestyle Considerations 
Cases of photosensitivity have been reported for patients on niraparib treatment. 
Participants must be informed on measures to decrease exposure to ultraviolet light, such 
as minimising time in direct sunlight unless wearing hats and long-sleeves and 
application of sun protection creams. 
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study 
but are not subsequently entered in the study. A minimal set of screen failure information 
is required to ensure transparent reporting of screen failure participants to meet the 
Consolidated Standards of Reporting Trials publishing requirements and to respond to 
queries from regulatory authorities. Minimal information includes demographics, screen 
failure details, eligibility criteria, any protocol deviations, and any SAEs. 
Individuals who do not meet the criteria for participation in this study (screen failure) 
may be rescreened. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 94 of 213 
6. 
STUDY TREATMENTS(S) AND CONCOMITANT 
THERAPY 
6.1. 
Study Treatment(s) Administered 
The dosing regimens for niraparib in Part 1B and Part 2 under Protocol Amendment 05 
are shown in Table 7 in Section 2.6.3.1.  
Details for suspension and administration of the TfOS are included in the Pharmacy 
Manual. 
Dostarlimab is an IgG4-κ humanised mAb that binds with high affinity to PD-1 and will 
be supplied for all study parts as a solution for intravenous (IV) infusion in single-use 10-
mL vials containing 500 mg (50 mg/mL). 
Details about the investigational products are provided in Table 13. 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 95 of 213 
Table 13: 
Investigational Products 
Intervention name 
Dosage 
formulation 
Type 
Drug 
Drug 
Biologic 
Unit dose 
strength(s) 
Use 
IMP 
IMP 
IMP 
Authorised 
AxMP/ 
Unauthorised 
AxMP 
Not applicable 
Not applicable 
Not applicable 
Sourcing 
Provided centrally by 
the Sponsor  
Provided centrally by 
the Sponsor 
Provided centrally by 
the Sponsor  
Physical 
description 
(Packaging and 
Labelling; see 
Section 6.2.1) 
Dosage level(s) 
See Section 2.6.3.1, 
Table 7 
See Section 2.6.3.1, 
Table 7 
See Section 2.6.3.2 
Manufacturer 
WuXi STA (WuXi), 
China (DS, DP) 
Dishman, India (DS) 
Corden, Colorado, US 
(DS) 
Mayne Pharma, 
Raleigh, North 
Carolina, US (DP) 
Siegfried, Switzerland 
(DS) 
WuXi STA (WuXi), 
China (DS, DP)  
Corden, Colorado, US 
(DS) 
Dishman, India (DS) 
Siegfried, Switzerland 
(DS) 
WuXi Biologics 
(WuXi), Wuxi, China 
(DS) 
Ajinomoto Althea 
(Aji), San Diego, 
California, US (DP) 
Abbreviations: AxMP = auxiliary medicinal product; DP=drug product; DS=drug substance; IMP = investigational 
medicinal product; IV=intravenous; Non-IMP = non-investigational medicinal product; 
 
; US=United States. 
 
CCI
CCI
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 96 of 213 
6.2. 
Preparation/Handling/Storage/Accountability 
6.2.1. 
Study Treatment Packaging and Labelling 
Previously, niraparib 
 were used by participants in all cohorts of Part 1A 
and niraparib 
 was used by participants in Part 1B Cohort 1 under Protocol 
Amendment 03. TfOS will be used by participants under Protocol Amendment 05. 
Niraparib will be packed in high-density polyethylene bottles with child-resistant 
closures. 
 
 
The label text of the study treatments will comply with Good Manufacturing Practice and 
national legislation to meet the requirements of the participating countries. The study 
treatment will be open-label and non-participant-specific. 
6.2.2. 
Study Treatment Storage 
All study treatment supplies must be stored in accordance with the Pharmacy Manual 
instructions and package labelling. Until dispensed or administered to the participants, 
the study treatments will be stored in a securely locked area that is accessible only to 
authorised personnel. 
6.2.3. 
Administration 
Details on the administration of the study treatments can be found in the Pharmacy 
Manual. A summary is provided below. 
6.2.3.1. 
Niraparib 
Oral niraparib will be dispensed to participants on Day 1 of every 21 -day cycle 
beginning with Cycle 1 of the Treatment Period until the end of the Treatment Period, 
PD, unacceptable toxicity, withdrawal of consent/assent, Investigator’s decision to 
withdraw, or death. On day 1 of each cycle, niraparib should be administered while at the 
site and after completion of the dostarlimab infusion. 
Participants will be instructed to take their niraparib dose once daily at approximately the 
same time each day. Niraparib will be self-administered or administered to the child by 
the parent/caregiver. 
 
 
 The consumption of water and food 
(i.e., light meal) with niraparib is permissible. If a participant vomits or misses a dose of 
niraparib, a replacement dose should not be taken.  
CCI
CCI
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 97 of 213 
 
  
6.2.3.2. 
Dostarlimab 
Dostarlimab infusion will be administered before the niraparib dose at the study site on 
Day 1 of each 21-day treatment cycle (Q3W). Dostarlimab may be administered up to 3 
days before or after the scheduled Day 1 of each cycle after Cycle 1 due to administrative 
reasons. If dostarlimab is administered on Day 1 of the cycle, it will be administered after 
all procedures and assessments have been completed, unless otherwise indicated. 
Participant dosing with dostarlimab is based on assigned cohort and participant weight at 
Week 1 of each treatment cycle, 
. Actual 
dostarlimab dosing within ±10% of the calculated weight-based dose is acceptable. 
Dostarlimab will be administered through a 30-minute infusion. Sites should make every 
effort to target infusion timing to be as close to 30 minutes as possible. Given the 
variability of infusion pumps from site to site, however, a window between -5 minutes 
and +15 minutes is permitted, in the absence of any clinically significant infusion-related 
reaction that would necessitate interruption and/or increased infusion interval. 
Participants should remain under observation at the study site post-study treatment 
infusion per the judgement of the Investigator or as per institutional guidelines to monitor 
for potential infusion reactions or other AEs. 
6.2.4. 
Study Treatment Accountability 
The Investigator or designee is responsible for maintaining accurate dispensing records of 
the study treatments throughout the clinical study. 
Details of maintaining drug accountability, including information on the accountability 
log, will be provided in the Pharmacy Manual. 
The Study Monitor will assume the responsibility to reconcile the niraparib and 
dostarlimab study treatment accountability logs. The pharmacist will dispense niraparib 
and dostarlimab study treatment for each participant according to the protocol and 
Pharmacy Manual. 
6.2.5. 
Study Treatment Handling and Disposal 
At the end of study, when all participants have stopped protocol treatment, complete drug 
reconciliation per batch should be available at the site for verification in order to allow 
drug destruction or return procedure. After receiving Sponsor approval in writing, the 
investigational site is responsible for destruction of study treatment according to local 
regulations. If a site does not have the capability for on-site destruction, the Sponsor will 
provide a return for destruction service through a third party. Both the unused and 
expired study treatment must be destroyed, upon authorisation of the Sponsor, according 
to local regulations and procedures, and a copy of the destruction form must be filed in 
the study binder. 
The medication provided for this study is to be used only as indicated in this protocol and 
only for the participants entered in this study. 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 98 of 213 
• 
The Investigator or designee must confirm appropriate temperature conditions 
have been maintained during transit for all study treatment received and any 
discrepancies are reported and resolved before use of the study treatment. 
• 
Only participants enrolled in the study may receive study treatment and only 
authorised site staff may supply or administer study treatment.  
• 
All study treatments must be stored in a secure, environmentally controlled, and 
monitored (manual or automated) area in accordance with the labelled storage 
conditions with access limited to the Investigator and authorised site staff. 
• 
The Investigator, institution, or the head of the medical institution (where 
applicable) is responsible for study treatment accountability, reconciliation, and 
record maintenance (ie, receipt, reconciliation, and final disposition records). 
• 
Further guidance and information for the final disposition of unused study 
treatment are provided in the Pharmacy Manual.  
• 
Precaution will be taken to avoid direct contact with the study intervention. An 
MSDS describing occupational hazards and recommended handling precautions 
will be provided to the Investigator. In the case of unintentional occupational 
exposure notify the monitor, Medical Monitor and/or GSK study contact. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
This is a non-randomised, open-label study. 
6.4. 
Study Treatment Compliance 
When participants are dosed at the site, they will receive study treatment directly from 
the Investigator or designee, under medical supervision. The date and time of each dose 
administered in the clinic will be recorded in the source documents. The dose of study 
treatment and study participant identification will be confirmed at the time of dosing by a 
member of the study site staff other than the person administering the study treatment. 
A dosing diary was used during the first 2 treatment cycles for participants in Part 1A in 
order to monitor treatment compliance during the DLT observation phase for the 
 
 
Under Protocol Amendment 05, all participants treated with the niraparib 
 will be 
expected to record all 
 use in the dosing diary to permit ongoing monitoring of 
dosing compliance. 
6.5. 
Dose Modification 
Specific dose modifications are included in Section 4.7. Any required dose modifications 
should be captured in the eCRF. 
6.6. 
Treatment of Overdose 
Young children are much less likely to report an overdose. The Investigator should warn 
parents/caregivers to store the study treatment out of reach of children. 
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 99 of 213 
In the event of an overdose, the Investigator should: 
• 
Contact the Medical Monitor immediately. 
• 
Closely monitor the participant for AE/SAE and laboratory abnormalities until the 
investigational product can no longer be detected systemically. 
• 
Document the quantity of the excess dose as well as the duration of the overdosing 
in the case report form (CRF). 
Decisions regarding dose interruptions or modifications will be made by the Investigator 
in consultation with the Medical Monitor based on the clinical evaluation of the 
participant. 
6.7. 
Continued Access to Study Intervention After the End of the 
Study 
Given that the end of study overall occurs when the last participant completes their last 
visit or last procedure, there will be no participants on the study in any capacity at the 
time that end of study occurs and, therefore, no need to provide study treatment to any 
ongoing participant. 
6.8. 
Concomitant Therapy 
Any medication that the participant is receiving, including herbal and other 
non-traditional remedies, at the time of screening or during the study must be recorded 
along with:  
• 
Reason for use 
• 
Dates of administration including start and end dates 
• 
Dosage information including dose and frequency 
The Medical Monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 
6.8.1. 
Rescue Medications 
Participants should receive appropriate supportive care measures as deemed necessary by 
the treating Investigator, including but not limited to the items outlined below. 
Prophylactic cytokines (eg, G-CSF) should be administered according to current ASCO 
guidelines [Smith, 2015] (except in Cycle 1 per Section 6.8.2). 
Note: it may be necessary to perform additional procedures such as bronchoscopy, 
endoscopy, or skin photography as part of evaluation of the event. 
6.8.2. 
Prohibited Medications 
Known prior medications that exclude participants from participating in the study are 
described in the exclusion criteria (Section 5.2). 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 100 of 213 
Participants are prohibited from receiving the following therapies during the Screening 
and Treatment periods of this study: 
• 
Systemic anticancer or biological therapy.  
• 
Immunotherapy not specified in this protocol. 
• 
Local interventions (such as radiotherapy) to RECIST v1.1/INRC target lesions 
prior to PD (unless discussed with and approved by GSK’s Medical Monitor). 
• 
Investigational agents other than niraparib and dostarlimab. 
• 
Prophylactic cytokines (e.g., G-CSF) should not be administered in the first cycle 
of the study but may be administered in subsequent cycles according to local 
guidelines. 
• 
Systemic glucocorticoids for any purpose other than to manage symptoms of 
suspected imAEs. (Note: Use of inhaled steroids, local injection of steroids, topical 
steroids, and steroid eye drops are allowed.) If medically deemed necessary (e.g., 
acute asthma or chronic obstructive pulmonary disease exacerbation, prophylaxis 
for IV contrast if indicated), Investigators are allowed to use their judgment to treat 
participants with systemic steroids. In such cases, systemic steroids should be 
stopped at least 24 hours prior to the next dose of dostarlimab. 
The combination of niraparib with vaccines or immunosuppressant agents has not been 
studied. 
The data on niraparib in combination with cytotoxic medicinal products are limited. 
Therefore, caution should be taken if niraparib is used in combination with vaccines, 
immunosuppressant agents or with other cytotoxic medicinal products. 
Concomitant administration of dostarlimab and live vaccines are prohibited during the 
study and for a period of at least 180 days after the last dose. 
No other anticancer treatment is permitted during the course of the study treatment for 
any participant. Palliative radiotherapy (excluding the pelvic region and/or palliative 
radiotherapy encompassing >20% of the bone marrow within 1 week of the first dose of 
study treatment) is allowed for pre-existing small areas of painful metastases that cannot 
be managed with local or systemic analgesics, as long as no evidence of PD is present. 
The niraparib safety profile includes risk for thrombocytopenia; therefore, participants 
should be advised to use caution when taking anticoagulants (e.g., warfarin) and 
antiplatelet drugs (e.g., aspirin). 
No clinical drug interaction studies have been performed with niraparib. In vitro data and 
physiologically based PK (PBPK) modeling indicated no clinically relevant inhibition or 
induction of drug-metabolizing cytochrome P450 enzymes and no clinically relevant 
inhibition of most efflux transporters or uptake transporters. 
Niraparib is an inhibitor of MATE-1 and -2K with IC50 of 0.18 µM and ≤0.14 µM, 
respectively. Simulations using PBPK modeling indicate an expected >2-fold increase in 
exposure of metformin when administered with niraparib at 200 mg or 300 mg daily. 
Close monitoring of glycemia is recommended when starting or stopping niraparib in 
patients receiving metformin. A dose adjustment of metformin may be necessary.  

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 101 of 213 
Physicians should follow the current versions of the niraparib IB and the dostarlimab IB 
for information on the general management of the participants participating in the study. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 102 of 213 
6.8.3. 
Other Study Restrictions 
Participants who are blood donors should not donate blood during the study and for 
90 days after the last dose of study treatment. 
Participants should maintain a normal diet, unless modifications are required to manage 
an AE such as diarrhoea, nausea, or vomiting. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 103 of 213 
7. 
DISCONTINUATION OF STUDY TREATMENT AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of Study Treatment 
Participants may be discontinued from study treatment at any time. Participants who 
discontinue from study treatment will not be replaced, unless deemed unevaluable for 
assessment of DLT as defined in Section 4.3.  
Participants who discontinue study treatment will attend the EOT Visit no more than 7 
days following the decision to discontinue study treatment and a Safety Follow-up Visit 
30 (+7) days after the last dose of study treatment. Participants are expected to complete 
the Safety Follow-up Visit regardless of reason for study treatment discontinuation and 
even if they have started subsequent anticancer therapy. Initiation of alternative 
anticancer therapy does not require withdrawal from the study overall. During the long-
term Follow-up Assessment Period, participants will be followed via clinic visit or 
telephone contact (if an in-person visit is not possible) every 90 (±14) days after the last 
dose of study treatment for the first year, every 180 (±14) days for the subsequent 2 
years, and yearly (±14 days) for an additional 2 years (5 years total), until the start of 
alternative anticancer therapy (unless there is an ongoing AE/SAE that must be followed 
until resolved, stabilised, or otherwise explained), or until discontinuation of the 
participant from the study overall, is lost to follow-up (as defined in Section 7.4), or dies 
(whichever occurs earlier). 
Specific reasons for discontinuing treatment include the following, in addition to those 
indicated in Section 4.7. Discontinuation of study treatment does not require 
discontinuation of participation in the study overall. 
• 
AE, which may include DLTs and recurrence of AEs upon rechallenge with study 
treatment. 
• 
MDS/AML (as confirmed by a haematologist)  
• 
Second primary malignancies other than MDS/AML may require discontinuation 
to be assessed by the treating physician in agreement with the Sponsor. 
• 
Hypertensive crisis/PRES 
• 
if the participant is required to discontinue either niraparib or dostarlimab, then 
discontinuation of all study treatments is mandated. 
• 
if there is risk to the participant as judged by the Investigator, Sponsor, or both. 
• 
if the participant has had severe noncompliance with protocol as judged by the 
Investigator, Sponsor, or both. 
• 
if the participant becomes pregnant 
• 
if the participant withdraws assent and/or the parent(s)/guardian(s) withdraw 
consent 
• 
if the participant is lost to follow-up 
• 
if the participant dies 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 104 of 213 
• 
if the participant has PD according to RECIST v1.1 criteria or INRC (participants 
with neuroblastoma only) or symptomatic deterioration necessitating a change in 
therapy in the opinion of the Investigator (see below) 
• 
initiation of new alternative anticancer therapy 
There is accumulating evidence indicating clinical benefit in a subset of patients treated 
with immunotherapy despite evidence of PD (Nishino, 2015). Therefore, participants 
with radiologic evidence of PD who are clinically stable may continue study treatment at 
the Investigator’s discretion, after discussion with the participant’s legally acceptable 
representative, parent(s), and/or legal guardian and after consultation with the Sponsor, 
while awaiting confirmatory tumour imaging. Clinical stability is defined by the 
following criteria: 
• 
absence of signs and symptoms indicating clinically significant PD (including 
worsening of laboratory values) 
• 
absence of rapid PD 
• 
no decline in performance status 
• 
no progressive tumour at critical anatomical sites (e.g., cord compression) 
requiring urgent medical intervention. 
Repeat imaging should be performed at 4 to 6 weeks from the initial assessment of PD. If 
repeat imaging assessment following RECIST v1.1 or INRC (participants with 
neuroblastoma only), shows stable disease (SD), PR, or CR, participants can continue 
study treatment at the Investigator’s discretion and efforts should be made to return to the 
imaging visit schedule defined in the SoA. In the event that PD is confirmed (e.g., second 
overall response of PD per RECIST v1.1 or INRC), participants should discontinue study 
treatment. 
Participants who discontinue from all study treatments without documented PD will 
continue to receive follow-up assessments and tumour imaging as part of the study unless 
they are discontinued from the study overall. 
7.1.1. 
Liver Chemistry Stopping Criteria 
Study treatment will be discontinued for a participant if liver chemistry stopping criteria 
are met. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 105 of 213 
Figure 6: 
Phase I/II Liver Chemistry Stopping and Monitoring Event Algorithm  
 
 
Refer to Appendix 8 for Required Liver Safety Actions, Monitoring and Follow-up to 
Assess Causality of Liver Events and Appendix 9 for Liver Safety Drug Restart or 
Rechallenge Guidelines. 
7.1.2. 
QTc Stopping Criteria 
A participant who meets the bulleted criterion will be withdrawn from study treatment: 
• QTc >500 msec 
For participants with underlying bundle branch block, follow the discontinuation criteria 
listed in Table 14: 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 106 of 213 
Table 14: 
Bundle Branch Block QTc Discontinuation Criteria 
Baseline QTc with Bundle Branch 
Block 
Discontinuation QTc with Bundle Branch 
Block 
<450 msec 
>500 msec 
450 – 480 msec 
≥530 msec 
 
7.2. 
Withdrawal of Consent 
If consent is withdrawn (i.e., a participant withdrew assent and/or parent(s)/guardian(s) 
withdrew consent), then the participant/participant’s parent/guardian(s) will no longer be 
contacted by the Investigator. However, any information that can subsequently be found 
in the public domain may be used by the Investigator or a third party acting on behalf of 
the Investigator. 
7.3. 
Participant Discontinuation/Withdrawal from the Clinical 
Study 
• 
A participant may withdraw from the study at any time at their own request and/or 
at the request of their parent/guardian for any reason (or without providing any 
reason); reasons may include withdrawal of consent/assent, death, lost to follow-
up, study terminated by the Sponsor.  
• 
A participant may be withdrawn at any time at the discretion of the Investigator for 
safety, behavioural, or compliance reasons. This is expected to be uncommon. 
• 
At the time of discontinuing from the study, if possible, an early discontinuation 
visit should be conducted, as shown in the SoA. See SoA for data to be collected at 
the time of study discontinuation and follow-up and for any further evaluations 
that need to be completed. 
• 
The participant will be permanently discontinued both from the study treatment 
and from the study at that time. 
• 
If the participant withdraws consent for disclosure of future information, the 
Sponsor may retain and continue to use any data collected before such a 
withdrawal of consent. 
• 
If a participant withdraws from the study, the participant may request destruction 
of any samples taken and not tested for further research, and the Investigator must 
document this in the site study records. 
• 
Investigators will attempt to contact participants who do not return for scheduled 
visits or follow-up. 
• 
Participants who are withdrawn from the study because of AEs/SAEs must be 
clearly distinguished from participants who are withdrawn for other reasons. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 107 of 213 
Investigator will follow participants who are withdrawn from the study due to an 
AE/SAE until the event is resolved. 
7.4. 
Lost to Follow-Up 
A participant will be considered lost to follow-up if the participant repeatedly fails to 
return for scheduled visits and is unable to be contacted by the study site.  
The following actions must be taken if a participant fails to return to the clinic for a 
required study visit: 
• 
The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain 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, the participant will be 
considered to have withdrawn from the study. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 108 of 213 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
Timings for all procedures and assessments are provided in the SoA (Table 3). Sites are 
to consult with the GSK Medical Monitor for any procedure that is anticipated to be 
completed outside the required time window.  
8.1. 
Assessment of Efficacy 
8.1.1. 
Primary Efficacy Endpoint 
Not applicable. 
8.1.2. 
Secondary Efficacy Endpoints 
Efficacy of the combination of niraparib and dostarlimab is part of the secondary 
objectives of the study. Secondary efficacy endpoints include ORR and DOR as assessed 
by the Investigator per RECIST v1.1 (Eisenhauer, 2009; Schwartz, 2016) or INRC (Park, 
2017) (for participants with neuroblastoma only). 
8.1.2.1. 
Radiologic Assessments 
All participants will undergo serial radiologic assessments to assess tumour response in 
accordance with Table 3 and Table 4. 
Timing and Considerations for Radiologic Assessments 
Participants must have a baseline tumour assessment (CT or MRI*) of the chest, 
abdomen, pelvis, and any additional sites** as clinically indicated within 28 days prior to 
the first dose of study treatment. Participants with neuroblastoma must also have a 
baseline tumour assessment via MIBG-SPECT/CT or FDG-PET/CT within 42 days prior 
to the first dose of study treatment. 
*CT scans should be performed with contrast agents unless contraindicated for 
medical reasons. MRI of the abdomen and pelvis can be substituted for CT if MRI 
adequately depicts the disease. However, MRI of the chest should not be substituted 
for CT of chest even if IV contrast is contraindicated. In such a case, CT will be 
performed without contrast to evaluate the lung parenchyma. If MRI is used to 
follow-up bone lesion(s), it must be performed prior to any treatment that may affect 
bone marrow cellularity (e.g., G-CSF). PET/CT may be used according to RECIST 
v1.1 or INRC (participants with neuroblastoma only) guidelines with full-dose 
diagnostic CT and as clinically indicated. 
**A baseline brain scan (IV contrast-enhanced MRI [preferred] or IV contrast-
enhanced CT) is required for participants with previously treated brain metastases. 
(Participants with previously treated brain metastases may participate under the 
conditions detailed in exclusion criterion 5 in this master protocol and in the 
exclusion criteria of each cohort-specific supplement for Part 2). 
Tumour assessments by CT or MRI of sites involved by disease at baseline and of any 
additional sites as clinically indicated will be done postbaseline, as will MIBG-
SPECT/CT or FDG-PET/CT tumour assessments (participants with neuroblastoma only). 
Tumour assessments should be conducted every 9 weeks (every 63 [±7] days) from the 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 109 of 213 
start of study treatment for the first 12 months and then every 12 weeks (every 84 [±7] 
days) thereafter, or more frequently if clinically indicated, until documented PD, the start 
of alternative anticancer treatment, or discontinuation of participant from overall study 
participation (eg, death, participant’s request, loss to follow-up), whichever comes first. 
Tumour assessments should be scheduled using the date of the first dose of study 
treatment as the reference date for all time points and are not to be scheduled based on 
the date of the previous imaging time point. Imaging assessment delay to conform to 
study treatment delay is not permitted. Participants who have already demonstrated 
documented PD as per RECIST v1.1 or INRC (participants with neuroblastoma only) do 
not need to have tumour assessments repeated at the EOT Visit or during the 
Post-Treatment FUP. Participants who do not have documented PD at time of study 
treatment discontinuation will continue to undergo tumour assessments on their original 
schedule (i.e., every 9 weeks [every 63 ±7 days] from the start of study treatment for the 
first 12 months and then every 12 weeks [every 84 ±7 days] thereafter, until documented 
PD, start of alternative anticancer treatment, or discontinuation from overall study 
participation [e.g., death, participant’s request, or participant is lost to follow-up], 
whichever comes first).  
Bone scan, whole body MRI, or PET scan will be carried out at baseline for all 
participants in Part 1 (excluding participants with neuroblastoma) and in the Part 2 
Osteosarcoma Expansion Cohort within 84 days prior to the first dose of study treatment 
in order to detect bony sites of disease. Subsequent assessments are to be performed 
during the Treatment Period when clinically indicated (i.e., participant describes new or 
worsening bone pain, or other signs or symptoms of new/progressing bone metastases are 
present). If the baseline bone scan, whole body MRI, or PET scan is positive for 
metastatic bone disease, a repeat assessment is required for confirmation of PR or CR. 
Participants who have a PR or CR while on treatment and who discontinue treatment 
prior to the next disease assessment must have all appropriate follow-up disease 
assessments to confirm the observed response no sooner than 4 weeks (28 days) after the 
first observation. 
Radiologic assessments obtained per the standard of care prior to enrolment into the 
study do not need to be repeated and are acceptable to use as baseline evaluations if all of 
the following conditions are met: (1) the CT or MRI tumour assessments were obtained 
within 28 days prior to the first dose of study treatment/the MIBG-SPECT/CT or FDG-
PET/CT tumour assessments were obtained within 42 days prior to the first dose of study 
treatment (participants with neuroblastoma only)/the bone scan, whole body MRI, or PET 
tumour assessments were obtained within 84 days prior to the first dose of study 
treatment (Part 1 [excluding participants with neuroblastoma] and in the Part 2 
Osteosarcoma Expansion Cohort), (2) the assessments were performed using the method 
requirements outlined in RECIST v1.1 or INRC (participants with neuroblastoma only), 
(3) the same imaging technique/modality must be used to follow identified lesions 
throughout the study for a given participant, and (4) appropriate documentation indicating 
that these radiologic tumour assessments were performed as standard of care is available 
in the participant’s source notes. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 110 of 213 
Clinical assessment of superficial lesions should be carried out on the same date as the 
imaging studies or no later than 3 days thereafter and must be recorded in the 
participant’s eCRF. 
Participant scan data are not routinely collected in this study. However, such data may be 
requested under special circumstances, such as during investigation of a significant safety 
event.  
8.1.2.1.1. Evaluation of Tumour Response 
Evaluation of tumour response will be according to RECIST v.1.1 guidelines or INRC 
(for participants with neuroblastoma only). 
8.1.2.2. 
Bone Marrow Assessments 
Participants with neuroblastoma will undergo bone marrow assessment in accordance 
with Table 3. If positive at baseline, bone marrow samples will be obtained every 9 
weeks (every 63 [±7] days) following the start of study treatment for the first 12 months 
and then every 12 weeks (every 84 [±7] days) thereafter, or more frequently if clinically 
indicated, until documented PD, the start of alternative anticancer treatment, or 
discontinuation from overall study participation (e.g., death, participant’s request, loss to 
follow-up), whichever comes first.  
Bone marrow assessments obtained per the standard of care prior to enrolment into the 
study do not need to be repeated and are acceptable to use as baseline evaluations if the 
assessments were obtained within 28 days prior to the first dose of study treatment. 
8.1.2.3. 
ORR Based on Investigator Assessment 
ORR based on Investigator assessment is defined as the proportion of participants with a 
best overall response (BOR) of confirmed CR or PR as determined by the Investigator 
using RECIST v1.1 or INRC (for participants with neuroblastoma only).  
8.1.2.4. 
Duration of Response 
DOR is defined as the time from first documentation of confirmed response (CR or PR) 
until the time of first documented PD by RECIST v1.1 or INRC (for participants with 
neuroblastoma only) based on Investigator assessment or death (whichever occurs first). 
This will only be calculated for participants who have a BOR of confirmed CR or PR. 
Participants who do not experience PD or die after they have had a response are censored 
at the date of their last tumour assessment.  
8.2. 
Assessment of Safety 
Planned time points for all safety assessments are provided in the SoA. 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 111 of 213 
At some timepoints, the protocol may specify that blood samples for clinical care (i.e., 
clinical chemistry, haematology, pregnancy) and for study-related research (PK, 
exploratory biomarkers) be obtained during a single study visit. In the event of concern 
for excessive blood volume withdrawal, sample collection should be prioritised as 
follows: 
1. clinical care 
2. niraparib PK 
3. dostarlimab PK, ADA, and NAb 
8.2.1. 
Safety Parameters 
Safety parameters will include the incidence of treatment-emergent adverse events 
(TEAEs), SAEs, study treatment-related SAEs, imAEs and AESIs. Clinical laboratory 
assessments (haematology, chemistry, coagulation, thyroid function), urinalysis (if 
obtained), vital sign measurements, performance status, ECG parameters, observations 
during physical examination, and use of concomitant medications will be collected. 
All safety parameters will be performed in accordance with Table 3. 
8.2.2. 
Demographic/Medical History 
Demographic and baseline characteristics consist of those variables that are assessed at 
screening/baseline. Participant demographics consist of gestational age (for participants 
≤2years of age at screening), race, ethnicity, and sex. 
Collection of sex, race and ethnicity data is necessary to assess and monitor the diversity 
of the trial participants, and to determine if the trial participants are truly representative of 
the impacted population. 
8.2.3. 
Disease History 
For disease history, the following will be documented: 
• 
date of initial diagnosis 
• 
tumour type 
• 
stage at time of initial diagnosis 
• 
last relapse date 
8.2.4. 
Medical and Surgical History 
Major medical and surgical history (including prior anticancer treatments and surgeries 
for the disease under study) will be collected. Details of any other prior invasive 
malignancy will be collected. Medical and surgical history will be obtained by 
interviewing the participant or the participant’s legally authorised representative (LAR) 
or by reviewing the participant’s medical records. 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 112 of 213 
8.2.5. 
Electrocardiogram 
Standard 12-lead ECGs will be performed in accordance with Table 3 using an ECG 
machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc 
intervals. ECG should be repeated at Cycle 3 Week 1 and EOT, as well as during the 
Treatment or Follow-up Periods if clinically indicated. 
8.2.7. 
Physical Examination 
Physical examinations and symptom-directed physical examinations will be performed in 
accordance with Table 3. Any physical examination abnormalities assessed as clinically 
significant should be recorded as an AE or SAE. If SAE criteria are met, the finding 
should be recorded and reported according to the SAE reporting process (see 
Appendix 2). 
8.2.8. 
Vital Signs, Height, and Weight 
Vital signs, height, and weight will be measured in accordance with Table 3. Vital signs 
will include temperature, blood pressure, heart rate, and respiratory rate. All vital signs 
will be taken before, every 15 to 30 minutes during, and at the end of every dostarlimab 
infusion. Throughout the Treatment Period, all vital signs will be monitored at Week 1 of 
each cycle even if dostarlimab is not administered. In addition, for the first 8 weeks of the 
Treatment Period (up to and including Cycle 3 Week 2), all vital signs will be monitored 
at Week 2 and Week 3 of each cycle. Height and weight will be measured at screening, 
Day 1 of each cycle, EOT, Safety Follow-up, and during the Follow-up Assessment 
Period. 
Any vital sign abnormalities assessed as clinically significant should be recorded as an 
AE or SAE. If SAE criteria are met, the finding should be recorded and reported 
according to the SAE reporting process (see Appendix 2). 
8.2.9. 
Pregnancy Testing 
Niraparib is known to have properties that require the participant to use contraception and 
may have adverse effects on a foetus in utero. It is not known if dostarlimab may have 
adverse effects on a foetus in utero in humans. However, murine models of allogeneic 
pregnancy showed that blockade of PD-L1 signalling can eliminate foetomaternal 
tolerance and cause spontaneous abortion as indicated by increase in embryo resorption 
and a reduction in litter size (D’Addio, 2011). Human IgG4 antibodies are known to cross 
the placental barrier. Dostarlimab, being an IgG4, has the potential to be transmitted from 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 113 of 213 
the mother to the developing foetus. Therefore, there is a risk associated with the 
administration of dostarlimab to WOCBP. 
If a participant is of childbearing potential, a urine or serum pregnancy test will be 
performed in accordance with Table 3 irrespective of prior medical treatment. The results 
from these tests must be available and negative before study treatment is administered. 
Additional pregnancy testing may be necessary if required by local practices or 
regulations or if potential pregnancy is suspected. 
Any pregnancies that occur in female participants within 180 days after the last dose of 
study treatment or in partners of male participants within 90 days after the last dose of 
study treatment are to be reported as described in Section 8.3.5. 
8.2.10. 
Performance Status 
Performance status will be assessed using the Karnofsky scale for participants >16 years 
of age and the Lansky scale for participants ≤16 years of age in accordance with Table 3.  
8.2.11. 
Psychological Assessments 
Psychological assessments will be performed in accordance with Table 3 and as per local 
standard of care.  
8.2.12. 
Laboratory Assessments 
Laboratory variables will be determined in accordance with Table 3. The list of clinical 
laboratory tests to be performed is provided in Table 15. Parameters must be measured 
within 7 days prior to Cycle 1 Day 1 to confirm eligibility. These tests will be performed 
by the local laboratory at the clinical site. If Cycle 1 Day 1 is no more than 7 days after 
sample collection for Screening, these samples do not need to be collected again for 
Cycle 1 Day 1, unless clinically warranted. (Note: Baseline platelet count of 100 000/µL 
is considered acceptable for use in this trial considering age-related differences in platelet 
counts and impact of prior therapies.)  
Any abnormal laboratory value assessed as clinically significant should be recorded as an 
AE. If SAE criteria are met or if the laboratory abnormality is an AESI, the event should 
be recorded and reported according to the SAE reporting process (see Appendix 2). 
Haematologic, blood chemistry, and coagulation factor testing may occur more 
frequently than is specified in Table 3, according to local standard of care, if medically 
indicated per Investigator judgment, or if the event meets the criteria for study treatment 
dose modification (see Section 4.7). Additional tests may be performed at a laboratory 
facility other than the study site, but the test results must be reported to the study site, the 
study site must keep a copy of test results with the participant’s study file, and the results 
must be entered into the eCRF. 
Any suspected case of MDS/AML reported while a participant is receiving treatment or 
being followed for post-treatment assessments must be referred for evaluation to a local 
haematologist to perform bone marrow aspirate and biopsy as per local standards of 
practice. The study site must receive a copy of the haematologist’s report of 
aspirate/biopsy findings, which must include a classification according to WHO, and 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 114 of 213 
other sample testing reports related to MDS/AML. Report data will be entered in the 
appropriate eCRF pages, and the site must keep a copy of all reports with the 
participant’s study file. If a diagnosis of MDS/AML is confirmed by a haematologist, the 
participant must permanently discontinue study treatment. 
Any suspected case of second primary malignancy (new malignancies other than 
MDS/AML) reported while a participant is receiving treatment or followed for post-
treatment assessments must be investigated, including obtaining and documenting a 
histological diagnosis. Testing completed as part of standard of care is sufficient as long 
as the methods are deemed acceptable after consultation with the GSK Medical Monitor. 
If clinically significant values do not return to normal/baseline within a period of time 
judged reasonable by the Investigator, the etiology should be identified, and the Sponsor 
notified. 
If laboratory values from non-protocol-specified laboratory tests performed at the 
institution’s local laboratory require a change in participant management or are 
considered clinically significant by the Investigator (e.g., SAE or AE or dose 
modification), then the results must be recorded. 
Table 15: 
Safety Laboratory Assessments 
Laboratory 
Assessments 
Parameters 
Haematology 
CBC: 
• 
haemoglobin 
• 
platelet count 
• 
white blood cell count 
• 
differential white blood cell 
count* 
Coagulation factors: 
• 
international normalised 
ratio 
• 
activated PTT 
 
Blood 
Chemistry 
Sodium, potassium, chloride, calcium, magnesium, glucose, total bilirubin, 
ALP, AST, ALT, total protein, albumin, creatinine, urea or blood urea 
nitrogen, amylase, thyroid function (thyroid-stimulating hormone [TSH], 
triiodothyronine [T3] or free triiodothyronine [FT3], and free thyroxine 
[FT4] or equivalent). 
* 
Either absolute counts or percentages may be recorded for differential values. 
8.2.13. 
Drug Screen 
Not applicable. 
8.2.14. 
Viral Disease Testing 
 
 
 or in response to any future requests from 
local health authorities) or if warranted by participant’s history in accordance with 
Table 3. 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 115 of 213 
8.3. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and 
Other Safety Reporting 
The definitions of an AE, SAE, TEAE, and AESI can be found in Appendix 2. DLTs for 
Part 1 are defined in Section 4.3. 
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, 
or the participant’s LAR). 
The Investigator and any qualified designees are responsible for detecting, documenting, 
and reporting events that meet the definition of an AE, SAE, or AESI and remain 
responsible for following up all events. 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 2. 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE Information 
• 
All AEs will be collected from the signing of the informed consent form 
(ICF)/assent until 30 days after the last dose of study treatment and SAEs will be 
collected from the signing of the ICF/assent until 90 days after the last dose of 
study treatment (or to a minimum of 30 days after the last dose of study treatment 
if the participant starts alternative anticancer treatment) at the time points specified 
in Table 3. However, any SAEs assessed as related to study participation (e.g., 
study treatment, protocol-mandated procedures, invasive tests, or change in 
existing therapy) or related to study treatment will be recorded from the signing of 
the ICF/assent through the Follow-up Assessment Period as specified in Table 3.  
• 
Medical occurrences that begin before the start of study treatment but after 
obtaining informed consent/assent will be recorded as Medical History/Current 
Medical Conditions, not as AEs. 
• 
All SAEs will be recorded and reported to the Sponsor or designee immediately 
and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 2. The Investigator will submit any updated SAE data to the Sponsor 
within 24 hours of it being available. 
• 
Investigators are not obligated to actively seek information on 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, the investigator must record it in the medical records per the local 
country requirements.  If the investigator considers the event to be reasonably 
related to the study treatment or study participation, the Investigator must promptly 
notify the Sponsor. 
8.3.2. 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended 
and nonleading verbal questioning of the participant or participant’s parent/guardian is 
the preferred method to inquire about AE occurrence. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 116 of 213 
Study site staff should instruct the legal guardians and caregivers on how to report signs 
and symptoms (e.g., crying and pain) in the individual paediatric participant. They will be 
instructed to report both specific and non-specific symptoms (including vomiting, 
diarrhoea, sleepiness, variation in the intensity and pattern of crying, etc.). These non-
specific symptoms may be the only manifestations of some adverse reaction observed in 
children or adolescents. Care should be taken that the clinical presentation of adverse 
reactions is not misinterpreted as the manifestation of a pre-existing or unrelated 
condition.  
Moreover, symptoms that are dependent on participant communication ability (e.g., 
nausea, pain, mood alterations) in younger or mentally disabled children could potentially 
be at risk for under- or misreporting. 
8.3.3. 
Follow-Up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow each 
participant at subsequent visits/contacts. All ongoing AEs and SAEs will be followed, 
regardless of start of alternative anticancer therapy, until the event is resolved, stabilised, 
or otherwise explained or until the participant has withdrawn consent to the study overall, 
is lost to follow-up (as defined in Section 7.4), or has died. Further information on 
follow-up procedures is given in Appendix 2. 
8.3.4. 
Regulatory Reporting Requirements for SAEs 
• 
Prompt notification by the Investigator to the Sponsor of an SAE is essential so 
that legal obligations and ethical responsibilities toward the safety of participants 
and the safety of a study treatment under clinical investigation are met.  
• 
The Sponsor has a legal responsibility to notify both the local regulatory authority 
and other regulatory agencies about the safety of a study treatment under clinical 
investigation. The Sponsor will comply with country-specific regulatory 
requirements relating to safety reporting to the regulatory authority, Institutional 
Review Boards (IRB)/Independent Ethics Committees (IEC), and Investigators. 
• 
An Investigator who receives an Investigator safety report describing an SAE or 
other specific safety information (eg, summary or listing of SAEs) from the 
Sponsor will review and then file it along with the IB and will notify the IRB/IEC, 
if appropriate according to local requirements. 
• 
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. 
• 
Investigators have to report to the Sponsor pregnancies, medication errors, abuse 
and misuse even in an absence of an AE/SAE as these may be subjected to local 
regulatory reporting requirements for the Sponsor. 
8.3.5. 
Pregnancy 
• 
Details of all pregnancies in female participants and, if indicated, female partners 
of male participants who receive study treatment will be collected after the start of 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 117 of 213 
study treatment and until 180 days after the last dose of study treatment in female 
participants and 90 days after the last dose of study treatment for female partners 
of male participants. 
• 
If a pregnancy is reported, the Investigator will record pregnancy information on 
the appropriate form and submit it to the Sponsor within 24 hours of learning of 
the pregnancy of the female participant or female partner of male participant (after 
obtaining the necessary signed informed consent from the female partner). 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. 
• 
Abnormal pregnancy outcomes (eg, spontaneous abortion, foetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs and will be 
reported as such. 
• 
The participant/pregnant female partner will be followed to determine the outcome 
of the pregnancy. The Investigator will collect follow-up information on the 
participant/pregnant female partner and the neonate, and the information will be 
forwarded to the Sponsor. 
• 
Any post-study pregnancy-related SAE considered reasonably related to the study 
treatment by the Investigator will be reported to the Sponsor as described in 
Section 8.3.4. While the Investigator is not obligated to actively seek this 
information in former study participants/pregnant female partners, the Investigator 
may learn of an SAE through spontaneous reporting. 
8.3.6. 
Adverse Events of Special Interest (AESI) 
AESIs must be recorded as such on the eCRF. The definitions of AESIs can be found in 
Appendix 2. 
The following AESIs for niraparib should be reported to the Sponsor throughout the 
Treatment Phase of the study, Safety Follow-up, and the long-term Follow-up 
Assessment Period: 
• 
MDS and AML 
• 
Second primary malignancy 
There are no AESIs for dostarlimab. 
8.4. 
Pharmacokinetics, Immunogenicity, and Biomarkers  
Blood samples to assess niraparib PK, dostarlimab PK, and dostarlimab ADAs and NAb 
will be collected from all participants pre- and postdose at the time points specified in 
Table 3. In addition, blood samples will be collected for exploratory biomarker analyses 
from participants with a body weight ≥12.5 kg and either neuroblastoma or osteosarcoma. 
The maximum blood volume for each sample for PK, ADA, NAb, and/or exploratory 
biomarker assessment is 0.8 mL/kg, and the maximum total blood volume allowed for 
PK, ADA, NAb, and/or exploratory biomarker assessments is 1.8 mL/kg per 3-week 
cycle.  

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 118 of 213 
In the event of concern for excessive blood volume withdrawal, sample collection should 
be prioritised as outlined in Section 8.2.  
GSK may store samples for up to 20 years after the end of the study to achieve study 
objectives (including for genetic testing; Section 8.5). Additionally, with participants’ 
consent, samples may be used for further research by GSK or others such as universities 
or other companies to contribute to the understanding of neuroblastoma or osteosarcoma 
or other diseases, the development of related or new treatments, or research methods. 
8.4.1. 
PK Sample Collection 
 
, and blood (serum) samples for evaluation of dostarlimab concentrations 
will be obtained at the time points specified in Table 3.  All PK samples once collected 
(regardless of dosing) may be analyzed if the sample date and time have been recorded, 
provided the necessary informed consent from the participant remains in effect.  
Description of the PK analysis is summarised in Section 9.3.3.3. 
8.4.2. 
Immunogenicity Sample Collection 
Blood samples for the evaluation of dostarlimab ADAs and NAb with associated drug 
concentration will be obtained at the time points specified in Table 3. Serum samples for 
the determination of anti-dostarlimab antibodies will be aliquots of the same samples 
collected as for PK. ADAs will be analysed in a tiered approach (i.e., screening, 
confirmation, titre, and neutralising antibody assay) using electrochemiluminescence, if 
appropriate. Description of the immunogenicity analysis is summarised in Section 
9.3.3.5. 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 119 of 213 
8.6. 
Health Economics 
Health Economics parameters are not evaluated in this study.  
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 120 of 213 
9. 
STATISTICAL CONSIDERATIONS 
Details of the statistical analyses presented below will be provided in the study’s 
statistical analysis plan (SAP). A change to the data analysis methods described in the 
protocol will require a protocol amendment only if it alters a principal feature of the 
protocol. The SAP will be finalised prior to database lock. Any changes to the methods 
described in the plan will be described and justified in the final clinical study report. 
All descriptive statistical analyses will be performed using the most recently released and 
available SAS statistical software, unless otherwise noted. For categorical variables, the 
number and percent of each category within a parameter will be calculated. For 
continuous variables, the sample size (n), mean, median, and standard deviation, as well 
as the minimum and maximum values, will be presented. Missing data will not be 
imputed unless otherwise stated. There will be a detailed description of participant 
disposition; participant demographics and baseline characteristics will be summarised. 
 
 
 
 
 
 
 
 
 
 
The detailed censoring rules for time-to-event variables will be included in the SAP. 
Additional statistical details for Part 2 of this study are presented in each cohort-specific 
supplement, as applicable. 
9.1. 
Sample Size Determination 
The sample size of approximately 56 participants in total is not based on formal statistical 
hypotheses, but is estimated based on an mTPI-2 dose escalation design for Part 1 
including approximately 7 cohorts (4 cohorts planned in Part 1A under Protocol 
Amendment 03 and 3 cohorts planned in Part 1B under Protocol Amendment 05 [8 
participants per each of the 7 cohorts]). Up to 5 additional participants may be enrolled to 
further evaluate the youngest participant group(s) if not represented. 
9.2. 
Analysis Populations 
For the purposes of analysis, the following analysis sets are defined as follows in 
Table 16.  
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 121 of 213 
Table 16: 
Analysis Sets 
Participant Analysis Set 
Description 
Safety 
The Safety Population is defined as all participants 
who receive at least 1 dose of either niraparib or 
dostarlimab. 
Intent-to-Treat (ITT) 
The ITT Population includes all participants who 
receive any study medication and have measurable 
baseline tumour assessment and/or, for neuroblastoma 
participants, MIBG-positive disease (or FDG-positive 
disease, for MIBG-nonavid tumours) at baseline.  
Modified Intent-to-Treat (mITT) 
The mITT Population includes all participants who 
receive any study medication, have measurable 
baseline tumour assessment, and/or, for 
neuroblastoma participants, MIBG-positive disease 
(or FDG-positive disease, for MIBG-nonavid-
tumours) at baseline, and have at least 1 postbaseline 
tumour assessment. 
Per Protocol  
The Per Protocol Population includes all participants 
in the mITT Population who do not have protocol 
violations during the study that may significantly 
impact the interpretation of efficacy results. 
DLT-evaluable 
The DLT-evaluable Population consists of 
participants in Part 1 who complete the DLT 
observation period through at least 2 cycles of study 
treatment (including ≥80% of the intended niraparib 
dose and ≥2 infusions of dostarlimab) or experience a 
DLT. 
Pharmacokinetic (PK) 
The PK Population includes all participants who 
receive at least one dose of study treatment and have 
at least one PK sample. PK Populations are defined 
separately for each agent. 
Immunogenicity (ADA) Population 
The ADA Population includes all participants who 
receive at least 1 dose of dostarlimab and who have at 
least 1 ADA sample with a result. 
Abbreviations: ADA=antidrug antibody; DLT=dose limiting toxicity; ITT=Intent-to-Treat; mITT=modified 
Intent-to-Treat; PK=pharmacokinetic. 
 
9.3. 
Statistical Analyses 
The SAP will be finalised prior to database lock and it will include a more technical and 
detailed description of the statistical analyses described in this section. This section is a 
summary of the planned statistical analyses of the most important endpoints including 
primary and key secondary endpoints. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 122 of 213 
9.3.1. 
General Considerations 
Participant disposition will be tabulated and will include the number of screened 
participants (ie, participant or the participant’s LAR, parent, or legal guardian has signed 
the ICF) and the number of participants in each study population for analysis, the number 
of participants who have discontinued treatment, and the reasons for treatment 
discontinuation. 
Demographics, baseline characteristics, concomitant medications, and medical history 
information will be summarised using descriptive statistics. 
All analyses will include summary statistics, including number of participants and 
percentage for categorical variables, and number of participants, mean, standard 
deviation, median, minimum, and maximum for continuous variables. Two-sided exact 
95% CIs based on the Clopper-Pearson method will be provided where appropriate 
(Clopper, 1934). Time-to-event analyses will be performed using Kaplan-Meier methods. 
The primary analysis set for the efficacy endpoints will be the mITT Population. 
9.3.2. 
Primary Endpoints 
For Part 1, the primary endpoint is DLTs. The incidence of DLTs will be summarised by 
study part and cohort for the DLT-evaluable Population. 
9.3.3. 
Secondary Endpoints 
9.3.3.1. 
Secondary Efficacy Endpoints  
The secondary efficacy endpoints are defined in Section 8.1.2. 
The number and proportion of participants with an objective response will be tabulated 
by dose cohort and overall. ORR will be calculated, along with its estimated 2-sided 
95% CI. Among the participants with a confirmed response, a time-to-event analysis of 
DOR will be performed using Kaplan-Meier method, including quartile estimates and 
two-sided 95% CI.  
9.3.3.2. 
Safety Analyses 
For all parts of the study, additional safety data will be summarised for the Safety 
Population.  
Study treatment duration and dose intensity will be summarised descriptively. The 
occurrence of dose interruption and dose modification will be tabulated.  
AEs will be classified according to Medical Dictionary for Regulatory Activities 
(MedDRA) v20.0 or later. All AEs occurring during the study will be included in by-
participant data listings and tabulated by MedDRA system organ class and preferred 
term. TEAE is defined as any AE with onset after the first administration of study 
treatment, throughout the Treatment Period, until 30 days after cessation of study 
treatment (90 days for SAEs) (or until the start of new anticancer treatment whichever 
occurs earlier), or any event that was present at baseline but worsened in intensity or was 
subsequently considered study treatment-related by the Investigator through the end of 
the study.  

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 123 of 213 
Safety parameters will include the incidence of TEAEs, related TEAEs, serious TEAEs, 
TEAEs of Grade 3 or greater by National Cancer Institute (NCI) Common Terminology 
Criteria for Adverse Events (CTCAE) v5, TEAEs leading to death, TEAEs leading to 
treatment discontinuation, and TEAEs leading to dose modification. AESIs will also be 
summarised and listed. No formal hypothesis-testing analysis of AE incidence rates will 
be performed. 
All AEs occurring on study will be listed in participant data listings. By-participant 
listings also will be provided for the following: participant deaths, SAEs, and AEs 
leading to withdrawal of study treatment. 
Clinical laboratory tests, vital signs, ECG results, physical examination findings, 
performance status, and concomitant medication usage will be listed per participant for 
each assessment, and descriptive statistics will be tabulated for selected safety 
parameters. 
9.3.3.3. 
PK Analysis 
The PK characteristics of niraparib and dostarlimab will be evaluated in the PK 
Population of this study using sparse blood sampling and population PK approaches. 
Serum concentrations of dostarlimab and 
 
 will be presented using descriptive statistics by dose cohort and overall. 
Summary statistics will include mean, standard deviation, coefficient of variation (CV), 
geometric mean, geometric mean CV, median, and minimum and maximum values. The 
 data may be used to evaluate the age-related 
development of niraparib metabolism in paediatric participants, if data permit. Niraparib 
and dostarlimab concentration‑time data will be analysed using a population approach. A 
nonlinear mixed effects model will be used to determine population pharmacokinetic 
parameters and identify relevant covariates (e.g., age, weight, or disease‑related 
covariates). The data from this study may be combined with data from other studies, 
which will be reported in a separate report. 
In addition, if deemed appropriate and if data permit, exposure-response relationships 
between exposure (e.g., dose, dose intensity, concentration, maximum concentration, or 
area under the concentration-time curve) and clinical activity and/or toxicity (e.g., 
response, [exploratory] biomarkers, safety event) may be explored using population 
modelling approaches. If data permit, the effects of covariates may be explored. Results 
of such analysis will be reported in a separate report. 
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 124 of 213 
 
 
 
9.3.3.5. 
Immunogenicity Analysis 
Immunogenicity of dostarlimab will be analysed only in the Immunogenicity Population. 
Minimally, ADA will be evaluated in all predose samples collected at each specified time 
point, as well as at EOT, at the Safety Follow‑up Visit (30 days post-treatment), and at 
the first Follow-up Visit (90 days post-treatment). The number and percent of participants 
who become positive for ADAs and who develop NAb will be summarised by treatment, 
visit/time and overall. 
9.3.4. 
Exploratory Endpoints 
The exploratory endpoints may include the assessment of biomarkers related to PARP 
inhibition and/or anti-PD-1 therapy and correlation with clinical outcome, based on 
provision of blood samples collected on study. Descriptive statistics may be used to 
summarise the ORR, DCR, PFS, and DOR in participants of different biomarker 
subpopulations. 
The data from this study may be combined with data from other studies and may be 
reported in a separate report.  
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 125 of 213 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
The regulatory and ethical considerations of the study are outlined in Appendix 1.  

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 126 of 213 
11. 
APPENDICES 
APPENDIX 1. REGULATORY, ETHICAL, AND STUDY 
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 Organisations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
• 
Applicable International Council for Harmonisation (ICH) Good Clinical Practice 
(GCP) Guidelines 
• 
Applicable laws and regulations 
• 
The protocol, protocol amendments, ICF, IB, and other relevant documents (eg, 
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.  
• 
Protocols and any substantial amendments to the protocol will require health 
authority approval prior to initiation except for changes necessary to eliminate an 
immediate hazard to study participants. 
• 
The Investigator will be responsible for the following: 
o 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 
o Notifying the IRB/IEC of SAE or other significant safety findings as required 
by IRB/IEC procedures 
o 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), European Medical Device 
Regulation 2017/745 for clinical device research (if applicable), and all other 
applicable local regulations 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 127 of 213 
Informed Consent Process 
• 
The Investigator or their representative will explain the nature of the study to the 
participant or their legally authorised representative (LAR) and answer all 
questions regarding the study.  
• 
Participants must be informed that their participation is voluntary. Participants or 
their LAR will be required to sign a statement of informed consent that meets the 
requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance 
Portability and Accountability Act (HIPAA) requirements, where applicable, and 
the IRB/IEC or study centre.  
• 
The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorised person obtaining the informed consent must 
also sign the ICF. 
• 
Participants must be re-consented to the most current version of the ICF(s) during 
their participation in the study.  
• 
A copy of the ICF(s) must be provided to the participant or their LAR.  
• 
The Investigator must obtain assent from the minor participant in addition to the 
consent provided by the participants’ parent(s)/LAR(s) when a minor can assent to 
participate in a study. The Investigator is also accountable for determining a 
minor's capacity to assent to participation in a research study according to the local 
laws and regulations. 
• 
The assent process will be tailored to the age of the potential participant and to any 
circumstances around the participant’s enrolment.  
GSK (alone or working with others) may use participant’s coded study data and samples 
and other information to carry out this study; understand the results of this study; learn 
more about the study treatments or about the study disease; publish the results of these 
research efforts; work with government agencies or insurers to have the study treatments 
approved for medical use or approved for payment coverage.  
Recruitment Strategy 
• 
Participants will be identified for potential recruitment using each research site’s 
clinical database prior to consenting to take part in this study. 
Data Protection 
• 
Participants will be assigned a unique identifier by the Sponsor. Any participant 
records or datasets that are transferred to the Sponsor will contain the identifier 
only; participant names or any information which would make the participant 
identifiable will not be transferred.  
• 
The participant/ participants’ parent(s)/LAR(s) must be informed that their 
personal study-related data will be used by the Sponsor in accordance with local 
data protection law. The level of disclosure must also be explained to the 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 128 of 213 
participant who will be required to give consent for their data to be used as 
described in the informed consent.  
• 
The participant must be informed that their medical records may be examined by 
Clinical Quality Assurance auditors or other authorised personnel appointed by the 
Sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities. 
• 
GSK will ensure protection of the personal data of the Investigator and site staff 
which is collected within the framework of and for the purpose of the study. 
• 
The contract between Sponsor and study sites specifies responsibilities of the 
parties related data protection, including handling of data security breaches and 
respective communication and cooperation of the parties. 
• 
Information technology systems used to collect, process, and store study-related 
data are secured by technical and organisational security measures designed to 
protect such data against accidental or unlawful loss, alteration, or unauthorised 
disclosure or access. 
• 
GSK has a global, internal policy that requires all GSK staff and complementary 
workers to report data incidents or breaches immediately, using dedicated tools. 
Clear procedures are defined for assessing and investigating data breaches to 
identify and to take appropriate remediation steps, to contain and to mitigate any 
risks for individuals resulting from a breach, in compliance with applicable laws. 
Committees Structure 
Early Safety Data Review AND/OR Committee 
For Part 1 and Part 2 Safety run-in of the study, in accordance with the Sponsor’s 
standard operating procedure, the DEC will monitor intervention-emergent data on an 
ongoing basis throughout study conduct for the purpose of ensuring the continued safety 
of participants enrolled in this study as described in detail in the Dose Escalation Plan. 
The DEC will be chaired by the GSK Medical Monitor and membership will include a 
GSK clinical scientist, GSK safety physician, GSK statistician, GSK pharmacokineticist, 
along with additional GSK designated staff as appropriate, representatives from the 
supporting contract research organization, and all participating Investigators. The DEC 
will review relevant safety and PK data generated immediately after all participants 
treated in the same dose cohort have passed the DLT period and on an ad hoc basis, as 
mandated by emerging study data. 
A data review committee (DRC) will be established for the purpose of monitoring safety 
and efficacy data from the Cohort Expansion part of the study (Part 2). The DRC may 
also take into consideration relevant findings from Part 1A and/or Part 1B if doing so 
would assist in review of data from Part 2. This committee will be composed of GSK 
staff who are independent of all aspects of the study. Members will include a clinical 
development physician, a safety physician, and a statistician. This committee will 
convene both periodically and on an ad hoc basis, as mandated by emerging study data. 
Comprehensive details of committee membership and its activities are described in a 
formal charter. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 129 of 213 
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 all Investigators who were involved in the study with the 
full summary of the study results, including a summary of trial results 
understandable to laypersons. The Investigator(s) is/are encouraged to share the 
layperson summary of results with the study participants, as appropriate. The full 
study report will be made available upon request, after decision on marketing 
authorisation by regulatory authorities. 
• 
Where required by regulation, the names of the Sponsor signatory and Investigator 
signatory will be made public. 
• 
GSK will provide the Investigator with participant-level line listings for their site 
only after completion of the full statistical analysis. 
• 
GSK intends to make anonymised 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 participant care. This helps ensure the 
data provided by trial participants are used to maximum effect in the creation of 
knowledge and understanding. Data will be shared with researchers in a non-
identifying way, and appropriate measures will be taken to protect personal 
information; these measures will comply with data protection and privacy laws that 
apply. Requests for access may be made through 
www.clinicalstudydatarequest.com. 
• 
The key design elements of this protocol and results summaries will be posted on 
www.ClinicalTrials.gov and/or GSK Clinical Study Register in compliance with 
applicable regulations/GSK policy. GSK will aim to register protocols summaries 
prior to study start and target results summaries submission within 12 months of 
primary/ study completion date. Where external regulations require earlier 
disclosure, GSK will follow those timelines.  
• 
Where required by regulation, summaries will also be posted on applicable 
national or regional clinical study registers. 
Data Quality Assurance 
• 
All participant data relating to the study will be recorded on printed or electronic 
case report form (eCRF) unless transmitted to the Sponsor or designee 
electronically (eg, laboratory data). The Investigator is responsible for verifying 
that data entries are accurate and correct by physically or electronically signing the 
CRF.  
• 
Quality tolerance limits (QTLs) will be pre-defined to identify systematic issues 
that can impact participant safety and/or reliability of study results and are 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 130 of 213 
documented in the Clinical Monitoring Plan. These pre-defined parameters will be 
monitored during the study and deviations from the QTLs and remedial actions 
taken will be summarised in the clinical study report. 
• 
The Investigator must permit study-related monitoring, audits, IRB/IEC review, 
and regulatory agency inspections and provide direct access to source data 
documents. 
• 
Monitoring details describing strategy including definition of study critical data 
items and processes (eg, risk-based initiatives in operations and quality such as 
Risk Management and Mitigation Strategies and Analytical Risk-Based 
Monitoring), methods, responsibilities and requirements, including handling of 
noncompliance issues and monitoring techniques (central, remote, or on-site 
monitoring) are provided in the Monitoring Plan. 
• 
The Sponsor or designee is responsible for the data management of this study 
including quality checking of the data. Detailed information about study data 
collection and management process, including systems used, can be found in the 
Data Management Plan. 
• 
The Sponsor assumes accountability for actions delegated to other individuals 
(e.g., contract research organisations [CRO]). 
• 
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. 
• 
Guidance on completion of eCRFs will be provided in eCRF completion 
guidelines. 
Source Documents 
• 
For this study there may be source data recorded directly into the eCRF (i.e., no 
prior written or electronic record of data is available). Data entered directly in the 
eCRF will be minimal and may include pregnancy information and results of 
COVID testing. 
• 
Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
Investigator’s site. 
• 
Data reported on the CRF or entered in the eCRF that are transcribed from source 
documents must be consistent with the source documents or the discrepancies must 
be explained. The Investigator may need to request previous medical records or 
transfer records, depending on the study. Also, current medical records must be 
available. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 131 of 213 
• 
Definition of what constitutes source data and its origin can be found in the source 
data agreement. 
• 
The Investigator must maintain accurate documentation (source data) that supports 
the information entered in the CRF. 
• 
Study monitors will perform ongoing source data verification to confirm that data 
entered into the eCRF by authorised 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.  
• 
Source data are shared with third parties contracted by GSK for external 
assessment or adjudication (e.g. endpoint adjudication committee; expert reader). 
Source data may also be shared, if necessary, with insurers. The non-exhaustive 
list of source data shared may include [discharge summaries, imaging reports, 
scans, pathology reports, biological specimens, ECG reports, lab reports, 
physician/consult notes, medication administration records; adverse event reports; 
safety monitoring reports; vital signs data, eCRFs; PK and biomarker data, etc.]. 
Participant names or any information that would make the participant identifiable 
or is not essential for the external assessment or adjudication will be redacted by 
the investigator sites prior to transfer. Details of the participant information 
redaction strategy are provided in the relevant third-party manuals and/or study 
plans. These source data will be used by the third party solely for the purpose 
indicated within this protocol. 
Study and Site Start and Closure 
First Act of Recruitment 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
The first act of recruitment is the first site open and will be the study start date. 
Study/Site Termination 
GSK or 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: 
For study termination: 
• 
Discontinuation of further study treatment development 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 132 of 213 
For site termination: 
• 
Failure of the Investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the Sponsor's procedures, or GCP guidelines. 
• 
Inadequate or no recruitment of participants (evaluated after a reasonable amount 
of time) by the Investigator. 
• 
Total number of participants included earlier than expected. 
• 
If the study is prematurely terminated or suspended, the Sponsor shall promptly 
inform the Investigators, the IECs/IRBs, the regulatory authorities, and any 
CRO(s) used in the study of the reason for termination or suspension, as specified 
by the applicable regulatory requirements. The Investigator shall promptly inform 
the participant and should assure appropriate participant therapy and/or follow-up. 
Publication Policy 
GSK seeks to publish medically or scientifically significant results in searchable peer-
reviewed scientific literature within 18 months from LSLV. GSK follows International 
Committee of Medical Journal Editors standards for authorship and uses good 
publications practices to guide publications. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 133 of 213 
APPENDIX 2. ADVERSE EVENTS AND SERIOUS ADVERSE 
EVENTS: DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND 
REPORTING 
Definition of AE 
AE Definition 
• 
An AE is any untoward medical occurrence in a clinical study participant, 
temporally associated with the use of a study treatment, whether or not 
considered related to the study treatment. 
NOTE: An AE can therefore be any unfavourable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of a study treatment. 
Events Meeting the AE Definition 
• 
Any abnormal laboratory test results (haematology, clinical chemistry), 
urinalysis (if obtained), or other safety assessments (e.g., ECG, radiologic scans, 
vital signs measurements), including those that worsen from baseline, 
considered clinically significant in the medical and scientific judgment of the 
Investigator (i.e., not related to progression of underlying disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either 
an increase in frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after study treatment administration even 
though it may have been present before the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected intervention- 
intervention interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
treatment or a concomitant medication. Overdose per se will not be reported as 
an AE/SAE unless it is an intentional overdose taken with possible suicidal/self-
harming intent. Such overdoses should be reported regardless of sequelae. 
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. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 134 of 213 
• 
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition 
that leads to the procedure is the AE. 
• 
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen. 
• 
Hospitalisation for elective treatment of a pre-existing condition (known or 
diagnosed before signing the informed consent) that did not worsen from 
baseline. 
Definition of SAE 
An SAE is defined as any serious AEs that, at any dose: 
a. Results in death 
b. 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. 
c. Requires inpatient hospitalisation or prolongation of existing hospitalisation 
In general, hospitalisation signifies that the participant has been admitted (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 hospitalisation are AE. If a 
complication prolongs hospitalisation or fulfils any other serious criteria, the event is 
serious. When in doubt as to whether “hospitalisation” occurred or was necessary, the 
AE should be considered serious. 
Hospitalisation for elective treatment of a pre-existing condition that did not worsen 
from baseline is not considered an AE. 
d. 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, diarrhoea, influenza, 
and accidental trauma (eg, sprained ankle) which may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption. 
e. Is a congenital anomaly/birth defect 
f. Other situations: 
Possible Hy’s Law case: ALT ≥ 3x ULN AND total bilirubin ≥ 2x ULN (>35% direct 
bilirubin) or INR >1.5 must be reported as SAE. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 135 of 213 
Medical or scientific judgment should be exercised by the Investigator in deciding 
whether SAE reporting is appropriate in other situations such as significant medical 
events that may jeopardise 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 for 
allergic bronchospasm, blood dyscrasias, convulsions, or development of intervention 
dependency or intervention abuse. 
Definition of an Adverse Event of Special Interest 
An AESI is any AE (serious or nonserious) that is of scientific and medical concern 
specific to the study treatment, for which ongoing monitoring and rapid communication 
by the Investigator to the Sponsor is appropriate.  
Niraparib AESIs 
AESIs for niraparib are the following:  
• 
Myelodysplastic syndrome (MDS) and AML 
• 
Second primary malignancy (new malignancies [other than MDS or AML]) 
Dostarlimab AESIs 
There are no AESIs for dostarlimab. 
Definition of TEAE 
TEAE Definition 
• 
A TEAE is an event that emerges during treatment, having been absent 
pre-treatment or worsens relative to the pre-treatment state. 
 
Recording and Follow-Up of AE and SAE 
AE and SAE Recording 
• 
When an AE/SAE occurs, it is the responsibility of the Investigator to review all 
documentation (eg, hospital progress notes, laboratory, and diagnostics reports) 
related to the event. 
• 
The Investigator will then record all relevant AE/SAE information. 
• 
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 required form. 
• 
There may be instances when copies of medical records for certain cases are 
requested by GSK. In this case, all participant identifiers, except for the 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 136 of 213 
AE and SAE Recording 
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 severity of AEs will be graded according to Common Terminology Criteria for 
Adverse Events (CTCAE) v5: 27 November 2017; National Institutes of Health (NIH), 
National Cancer Institute (NCI). The CTCAE severity Grades 1 through 5 provide 
unique clinical descriptions of severity of each AE. The CTCAE v5 is available on the 
NCI/NIH website. In general, NCI-CTCAE severity grades are as follows: 
• 
Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated; easily tolerated. 
• 
Grade 2: Moderate; minimal, local, or noninvasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living (ADLs; instrumental ADLs 
refer to preparing meals, shopping for groceries or clothes, using the telephone, or 
managing money). 
• 
Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalisation or prolongation of hospitalisation indicated; disabling; limiting 
self-care ADL (self-care ADLs refer to bathing, dressing and undressing, feeding 
self, using the toilet, taking medications, and being not bedridden). 
• 
Grade 4: Life-threatening consequences; urgent intervention indicated. 
• 
Grade 5: Death related to AE. 
A distinction should be made between serious and severe AEs. Severity is a measure of 
intensity, whereas seriousness is defined by the criteria presented in the Section 
‘Definition of SAE’. For example, a mild degree of gastrointestinal bleeding requiring 
an overnight hospitalisation for monitoring purposes may be considered an SAE but is 
not necessarily severe. Similarly, an AE that is severe in intensity is not necessarily an 
SAE. For example, alopecia may be assessed as severe in intensity but may not be 
considered an SAE. 
Assessment of Causality 
The Investigator is obligated to assess the relationship between study treatment and 
each occurrence of each AE/SAE. 
• 
A “reasonable possibility” of a relationship conveys that there are facts, 
evidence, and/or arguments to suggest a causal relationship, rather than a 
relationship cannot be ruled out. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 137 of 213 
AE and SAE Recording 
• 
The Investigator will use clinical judgment to determine the relationship. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and 
other risk factors, as well as the temporal relationship of the event to study 
treatment administration will be considered and investigated. 
• 
The Investigator will also consult the IB and/or Product Information, for 
marketed products, in their assessment. 
• 
For each AE/SAE, the Investigator must document in the medical notes that 
they have 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. 
• 
Where more than 1 intervention is administered in the same visit, the 
Investigator should specify, when possible, if the AE/SAE could be causally 
related to a specific study intervention. When a causal relationship to a specific 
study intervention cannot be determined, the Investigator should indicate the 
AE/SAE to be related to all interventions. 
• 
The Investigator may change their 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. 
Assessment Of Outcomes 
The Investigator will assess the outcome of all serious and nonserious unsolicited AEs 
recorded during the study as: 
• 
Recovered/resolved. 
• 
Recovering/resolving. 
• 
Not recovered/not resolved. 
• 
Recovered with sequelae/resolved with sequelae. 
• 
Fatal (SAEs only). 
 
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 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 138 of 213 
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. 
• 
New or updated information will be recorded in the originally submitted 
documents. 
• 
The Investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information. 
After the initial AE/SAE/AESI/pregnancy or any other event of interest, the 
Investigator is required to proactively follow each participant at subsequent 
visits/contacts. All SAEs, [and nonserious AESIs (as defined in the Section 8.3.6], 
will be followed until the event is resolved, stabilised, otherwise explained, or the 
participant is lost to follow-up. 
 
Follow-up during the study 
AEs/AESIs documented at a previous visit/contact and defined as not recovered/not 
resolved or recovering/resolving will be reviewed at subsequent visits/contacts as 
outlined in Section 8.3. 
If a participant dies during their participation in the study or during a recognised 
follow-up period, GSK will be provided with any available postmortem findings, 
including histopathology. 
Follow-up of pregnancies 
Pregnant participants/pregnant partners of male participants will be followed to 
determine the outcome of the pregnancy. At the end of the pregnancy, whether full-
term or premature, information on the status of the mother and child will be forwarded 
to GSK using the appropriate report form and the AE Report if applicable. Generally, 
the follow-up period does not need to be longer than 6 to 8 weeks after the estimated 
date of delivery. 
Regardless of the reporting period for SAEs in this study, if the pregnancy outcome is 
an SAE, it should always be reported as such. 
Furthermore, the Investigator must report any SAE occurring as a result of a post-study 
pregnancy that is considered by the Investigator to be reasonably related to the study 
intervention, to GSK as described in the Section ‘Reporting of SAE to GSK’. 
Updating of SAE, AESI, and pregnancy information after removal of write access 
to the participant’s eCRF 
When additional SAE, AESI, or pregnancy information is received after write access to 
the participant’s eCRF is removed, new or updated information should be recorded on 
the appropriate paper report, with all changes signed and dated by the Investigator. The 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 139 of 213 
updated report should be sent to the study contact for reporting SAEs (refer to the 
Section ‘Reporting of SAE to GSK’). 
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) to report the event within 24 hours. 
• 
The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
• 
The Investigator or medically-qualified sub-Investigator must show evidence 
within the eCRF (eg, check review box, signature, etc.) of review and 
verification of the relationship of each SAE to IP/study participation (causality) 
within 72 hours of SAE entry into the eCRF. 
• 
After the study is completed at a given site, the electronic data collection tool 
will be taken off-line to prevent the entry of new data or changes to existing 
data. 
• 
If a site receives a report of a new SAE from a study participant or receives 
updated data on a previously reported SAE after the electronic data collection 
tool has been taken off-line, then the site can report this information on a paper 
SAE form (see next section) or to the CRO by telephone. 
• 
Contacts for SAE reporting can be found in the local study contact information. 
SAE Reporting to GSK via Paper Data Collection Tool 
• 
Email/facsimile transmission of the SAE paper data collection tool is the 
preferred method to transmit this information to the Medical Monitor. 
• 
In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE data collection tool sent by 
overnight mail or courier service. 
• 
Initial notification via telephone does not replace the need for the Investigator to 
complete and sign the SAE data collection tool within the designated reporting 
time frames. 
• 
Contacts for SAE reporting can be found in the local study contact information. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 140 of 213 
APPENDIX 3. CONTRACEPTION GUIDELINES 
Definitions 
Women in the following categories are considered WOCBP (fertile): 
• 
Adolescents of childbearing potential: Tanner stage ≥2 (post-thelarche) irrespective 
of the occurrence of menarche or following menarche. 
• 
From the time of menarche until becoming postmenopausal unless permanently 
sterile (see below). 
Note: Menarche is the first onset of menses in a young female. Menarche is 
normally preceded by several changes associated with puberty including breast 
development and pubic hair growth. 
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 must discontinue HRT 
to allow confirmation of postmenopausal status before study enrolment. 
Permanent sterilisation methods (for the purpose of this study) include: 
• 
Documented hysterectomy 
• 
Documented bilateral salpingectomy 
• 
Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (eg, Mullerian agenesis, androgen insensitivity, gonadal dysgenesis), Investigator 
discretion should be applied to determining study entry. 
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle 
cannot be confirmed before first dose of study treatment, additional evaluation should be 
considered. 
Contraception Guidance 
Table 17: 
Contraceptives Allowed During the Study 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 141 of 213 
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE THE 
FOLLOWING: 
Highly Effective Methodsb that Have Low User Dependency 
• 
Implantable progestogen-only hormone contraception associated with inhibition of 
ovulationc 
• 
IUD 
• 
IUSc 
• 
Bilateral tubal occlusion 
• 
Azoospermic partner (vasectomised or due to a medical cause) 
o Azoospermia is a highly effective contraceptive method provided that the partner 
is the sole sexual partner of the WOCBP 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. 
Note: documentation of azoospermia for a male participant can come from the site 
personnel’s review of the participant’s medical records, medical examination, or 
medical history interview. 
Highly Effective Methodsb That Are User Dependent 
• 
Combined (oestrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulationc 
o oral 
o intravaginal 
o transdermal 
o injectable 
• 
Progestogen-only hormone contraception associated with inhibition of ovulationc 
o oral 
o injectable 
• 
Sexual abstinence 
Note: Sexual abstinence is considered a highly effective method only if defined as refraining 
from heterosexual intercourse during the entire period of risk associated with the study 
treatment. The reliability of sexual abstinence needs to be evaluated in relation to the duration 
of the study and the preferred and usual lifestyle of the participant. 
Abbreviations: CTFG=Clinical Trial Facilitation Group; IUD=intrauterine device; IUS=intrauterine 
hormone-releasing system; LAM=lactational amenorrhoea method. 
Note: Periodic abstinence (calendar, sympto-thermal, post-ovulation methods), withdrawal (coitus 
interruptus), spermicides only, and 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). 
a. 
Contraceptive use by men or 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 CTFG 
guidelines, acceptable contraceptive methods are limited to those which inhibit ovulation as the primary mode of 
action. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 142 of 213 
APPENDIX 4. GUIDELINES FOR ASSESSMENT OF DISEASE, 
DISEASE PROGRESSION AND RESPONSE CRITERIA – 
ADAPTED FROM RECIST 1.1 
Assessment Guidelines 
Assessment guidelines based on RECIST 1.1 (Eisenhauer, 2009; Schwartz, 2016) are 
presented in the following sections. 
Please note the following: 
• 
The same imaging method, including use of contrast when applicable, must be 
used throughout the study to evaluate a tumour lesion for a given participant. 
Contrast agents must be used in accordance with the Image Acquisition 
Guidelines. 
• 
All measurements should be taken and recorded in millimetres (mm), using a ruler 
or callipers. 
• 
Ultrasound is not a suitable modality of disease assessment. If new lesions are 
identified by ultrasound, confirmation by computed tomography (CT) or magnetic 
resonance imaging (MRI) is required. 
• 
Fluorodeoxyglucose-positron emission tomography (FDG-PET) is generally not 
suitable for ongoing assessments of disease. However, FDG-PET can be useful in 
confirming new sites of disease where a positive FDG-PET scan correlates with 
the new site of disease present on CT/MRI or when a baseline FDG-PET was 
previously negative for the site of the new lesion. FDG-PET or whole body MRI 
may also be used in lieu of a standard bone scan providing coverage allows 
interrogation of all likely sites of metastatic bone disease and FDG-PET is 
performed at all assessments. 
• 
If PET/CT is performed then the CT component can only be used for standard 
response assessments if performed to diagnostic quality, which includes the 
required anatomical coverage and prescribed use of contrast. The method of 
assessment should be noted as CT on the CRF. 
Clinical Examination: Clinically detected lesions will only be considered measurable 
when they are superficial (e.g., skin nodules). 
CT and MRI: Contrast-enhanced CT with 5 mm contiguous slices is recommended. 
Minimum size of a measurable baseline lesion should be twice the slice thickness, with a 
minimum lesion size of 10 mm when the slice thickness is 5 mm. MRI is acceptable, but 
when used, the technical specification of the scanning sequences should be optimised for 
the evaluation of the type and site of disease and lesions must be measured in the same 
anatomic plane by use of the same imaging examinations. Whenever possible the same 
scanner should be used. 
X-ray: In general, X-ray should not be used for target lesion measurements due to poor 
lesion definition. Lesions on chest X-ray may be considered measurable if they are 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 143 of 213 
clearly defined and surrounded by aerated lung; however chest CT is preferred over chest 
X-ray. 
Brain Scan: If brain scan is required, then IV contrast-enhanced MRI is preferable to IV 
contrast-enhanced CT. 
Bone Scan (typically bone scintigraphy): If a bone scan is performed and a new 
lesion(s) is equivocal, then correlative imaging (ie, X-ray, CT, or MRI) is required to 
demonstrate malignant characteristics of the lesion(s). 
Note: PET (FDG or fluoride) may be used in lieu of a standard bone scan providing 
coverage allows interrogation of all likely sites of metastatic bone disease and PET is 
performed at all assessments. 
Guidelines for Evaluation of Disease 
Measurable and Non-Measurable Definitions 
Measurable Lesion  
A non-nodal lesion that can be accurately measured in at least 1 dimension (longest 
dimension) of: 
• 
≥10 mm with MRI or CT when the scan slice thickness is no greater than 5 mm. If 
the slice thickness is greater than 5 mm, the minimum size of a measurable lesion 
must be at least double the slice thickness (eg, if the slice thickness is 10 mm, a 
measurable lesion must be ≥20 mm). 
• 
≥10 mm calliper/ruler measurement by clinical exam or medical photography.  
• 
≥20 mm by chest x-ray.  
Additionally, lymph nodes can be considered pathologically enlarged and measurable if: 
• 
≥15mm in the short axis when assessed by CT or MRI (slice thickness 
recommended to be no more than 5 mm). At baseline and follow-up, only the short 
axis will be measured. 
Non-measurable Lesion  
All other lesions including lesions too small to be considered measurable (longest 
diameter <10 mm or pathological lymph nodes with ≥10 mm and <15 mm short axis) as 
well as truly non-measurable lesions, which include: Leptomeningeal disease, ascites, 
pleural or pericardial effusions, inflammatory breast disease, lymphangitic involvement 
of the skin or lung, abdominal masses/abdominal organomegaly identified by physical 
exam that is not measurable by reproducible imaging techniques. 
Measurable Disease  
The presence of at least one measurable lesion. Palpable lesions that are not measurable 
by radiologic or photographic evaluations may not be utilised as the only measurable 
lesion. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 144 of 213 
 Baseline Definition of Target Lesions and Non-target Lesions 
Measurable lesions up to a maximum of 2 lesions per organ and 5 lesions in total, 
representative of all involved organs, should be identified as target lesions, and recorded 
and measured at baseline. These lesions should be selected based on their size 
(measurable diameters) and their suitability for accurate repeated measurements. 
All other lesions or sites of disease should be recorded as non-target lesions at 
Screening/baseline and should be followed qualitatively. Non-target lesions can be 
grouped by organ. Measurements are not required; instead, the status of non-target 
lesions should be determined as “present,” “absent”), or in rare cases, “unequivocal 
progression” during follow-up. 
Additional guidance for selection of target lesions and non-target lesions at 
Screening/baseline is presented below: 
• 
For selection of target lesions, paired organs such as the lungs or kidneys are each 
considered together as a single organ, and no more than 2 lesions should be 
recorded as target lesions within the pair. The skin and all lymph nodes are each 
considered a single organ for the purposes of target lesion selection. 
• 
Lymph nodes of pathologic size with short axis diameters of 10 mm to <15 mm 
should be recorded as non-target lesions. 
• 
Lesions identified by clinical assessment (superficial skin lesions) should only be 
followed as non-target lesions when other suitable target lesions are available. 
• 
Cystic lesions thought to represent cystic metastases should not be selected as 
target lesions when other suitable target lesions are available. 
• 
Lytic bone lesions or mixed lytic-blastic lesions with identifiable soft-tissue 
components that can be evaluated by CT or MRI can be considered measurable 
(soft-tissue component). Bone scans, FDG-PET scans, or x-rays are not considered 
adequate imaging techniques to measure soft-tissue components of bone lesions. 
Response Criteria 
Evaluation of Target Lesions 
Definitions for assessment of response for target lesion(s) are as follows: 
• 
Complete Response (CR): Disappearance of all target lesions. Any pathological 
lymph nodes must be <10 mm in the short axis. 
• 
Partial Response (PR): At least a 30% decrease in the sum of the diameters of 
target lesions, taking as a reference, the baseline sum of the diameters (eg, percent 
change from baseline). 
• 
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient 
increase to qualify for PD. 
• 
Progressive Disease (PD): At least a 20% increase in the sum of the diameters of 
target lesions, taking as a reference, the smallest sum of diameters recorded since 
the treatment started (e.g., percent change from nadir, where nadir is defined as the 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 145 of 213 
smallest sum of diameters recorded since treatment start). In addition, the sum 
must have an absolute increase from nadir of 5 mm. 
• 
Not Evaluable (NE): Cannot be classified by one of the 5 preceding definitions. 
Only relevant if, at the follow-up tumour assessment, any of the target lesions were 
not assessed or were NE, and criteria for PD have not been met considering 
evaluable target lesions. 
Notes: 
• 
A sum of diameters is calculated from the long-axis diameters of non-nodal lesions 
and short axis diameters of lymph nodes (as applicable). 
• 
If lymph nodes are documented as target lesions the short axis is added into the 
sum of the diameters (i.e., sum of diameters is the sum of the longest diameters for 
non-nodal lesions and the short axis for nodal lesions). When lymph nodes 
decrease to non-pathological size (short axis <10 mm) they should still have a 
measurement reported in order not to overstate progression. 
• 
If at a given assessment time point all target lesions identified at baseline are not 
assessed, sum of the diameters cannot be calculated for purposes of assessing CR, 
PR, or SD, or for use as the nadir for future assessments. However, the sum of the 
diameters of the assessed lesions and the percent change from nadir should be 
calculated to ensure that progression has not been documented. If an assessment of 
PD cannot be made, the response assessment should be NE. 
• 
All lesions (nodal and non-nodal) should have their measurements recorded even 
when very small (e.g., 2 mm). If lesions are present but too small to measure, 
5 mm should be recorded and should contribute to the sum of the diameters, unless 
it is likely that the lesion has disappeared in which case 0 mm should be reported. 
• If a lesion disappears and reappears at a subsequent time point it should continue 
to be measured. The response at the time when the lesion reappears will depend 
upon the status of the other lesions. For example, if the disease had reached a CR 
status, then PD would be documented at the time of reappearance. However, if the 
response status was PR or SD, the diameter of the reappearing lesion should be 
added to the remaining diameters and response determined based on percent 
change from baseline and percent change from nadir. 
• 
If a target lesion splits, the longest diameter (non-nodal)/short axis diameter 
(lymph node) of each portion should be measured and added to the target lesion 
sum of diameters. 
• 
If target lesions merge and it is not possible to capture maximum diameter 
measurements for the individual lesions, the long-axis diameter (non-
nodal)/short-axis diameter (lymph node) across the merged lesions should be 
recorded as the measurement for 1 of the merged lesions and 0 mm recorded for 
the other. 
Evaluation of Non-Target Lesions 
Definitions for assessment of individual non-target lesions status: 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 146 of 213 
• Present: At the follow-up tumour assessment, the non-target lesions is still present 
and has not increased enough to warrant a status of unequivocal progression. 
• Absent: This status should be used for non-nodal, non-target lesions that have 
disappeared at the follow-up tumour assessment and for lymph node non-target 
lesions that reduce to less than 10mm in short-axis diameter. 
• Unequivocal Progression: At the follow-up tumour assessment, the non-target lesion 
showed unequivocal worsening/progression. 
• Unable to evaluate: At the follow-up tumour assessment, the non-target lesion was 
not assessed (e.g. imaging did not cover the anatomical lesion location) or was NE 
(e.g., image quality was inadequate and the lesion could not be evaluated). 
Definitions for collective assessment of response for all non-target lesions are as follows: 
• 
Complete Response (CR): The disappearance of all non-target lesions. All lymph 
nodes identified as a site of disease at baseline must be non-pathological (e.g., 
<10 mm short axis). 
• 
Non-CR/Non-PD: The persistence of 1 or more non-target lesion(s) or lymph 
nodes identified as a site of disease at baseline ≥10 mm short axis. 
• 
Progressive Disease (PD): Unequivocal progression of existing non-target lesions.  
• 
Not Applicable (NA): No non-target lesions at baseline. 
• 
Not Evaluable (NE): Cannot be classified by one of the 4 preceding definitions. 
Notes: 
• 
In the presence of measurable disease, progression on the basis of solely non-target 
disease requires substantial worsening such that even in the presence of SD or PR 
in target disease, the overall tumour burden has increased sufficiently to merit 
discontinuation of therapy.  
• 
In the presence of non-measurable only disease consideration should be given to 
whether or not the increase in overall disease burden is comparable in magnitude 
to the increase that would be required to declare PD for measurable disease. 
• 
Sites of non-target lesions, which are not assessed at a particular time point based 
on the assessment schedule, should be excluded from the response determination 
(eg, non-target response does not have to be “Not Evaluable”). 
New Lesions 
New malignancies (i.e., new lesions) denoting disease progression must be unequivocal. 
Lesions identified in follow-up in an anatomical location not scanned at baseline are 
considered new lesions. 
Any equivocal new lesions should continue to be followed. Treatment can continue at the 
discretion of the Investigator until the next scheduled assessment. If at the next 
assessment the new lesion is considered to be unequivocal, progression should be 
documented. Note: the date of progression will be the date the unequivocal lesion was 
first identified as equivocal. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 147 of 213 
Evaluation of Overall Response 
Table 18 presents the overall response at an individual time point for all possible 
combinations of tumour responses per RECIST v1.1 in target and non-target lesions with 
or without the appearance of new lesions for participants with measurable disease at 
baseline. 
Table 18: 
Evaluation of Overall Response for Participants with Measurable 
Disease at Baseline 
Target Lesions 
Non-target Lesions 
New Lesions 
Overall Response 
CR 
CR or NA 
No 
CR 
CR 
Non-CR/Non-PD or 
NE 
No 
PR 
PR 
Non-PD or NA or NE No 
PR 
SD 
Non-PD or NA or NE No 
SD 
NE 
Non-PD or NA or NE No 
NE 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
Abbreviations: CR=complete response; PD=progressive disease; PR=partial response; NA=not applicable; 
NE=not evaluable; SD=stable disease. 
 
Notes: 
• 
Participants with a global deterioration of health status requiring discontinuation of 
treatment without objective evidence of disease progression at that time should be 
classified as having “symptomatic deterioration.” Objective response status is 
determined by evaluations of disease burden. Every effort should be made to 
document the objective progression even after discontinuation of treatment. 
• 
In some circumstances, it may be difficult to distinguish residual disease from 
normal tissue. When the evaluation of CR depends on this determination, it is 
recommended that the residual lesion be investigated (fine needle aspirate/biopsy) 
to confirm the CR. 
Confirmation Criteria 
To be assigned a status of confirmed PR or CR, a confirmatory disease assessment should 
be performed no less than 4 weeks (28 days) after the criteria for response are first met. 
Please refer to the Tumour Assessment Flowchart Table 4) for information on imaging 
requirements for response confirmation. 
 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 148 of 213 
APPENDIX 5. GUIDELINES FOR ASSESSMENT OF DISEASE, 
DISEASE PROGRESSION AND RESPONSE CRITERIA IN 
PARTICIPANTS WITH NEUROBLASTOMA – ADAPTED FROM 
REVISED INTERNATIONAL NEUROBLASTOMA RESPONSE 
CRITERIA (INRC) 
A National Cancer Institute–appointed executive planning committee, selected a panel of 
52 international Investigators from 13 countries with oncology, pathology, radiology, 
nuclear medicine, surgery, biology, and statistical expertise to develop and implement a 
revised consensus response criteria for neuroblastoma (Park, 2017). 
Assessment Guidelines:  
• 
Anatomic imaging (CT/MRI) will be used for defining measurable primary tumour 
sites and soft tissue metastatic lesions (non-lymph node tumour lesions and 
malignant lymph nodes) and response in accordance with RECIST criteria (Refer 
to Appendix 4 Assessment Guidelines and Definitions of Measurable Lesions). 
• 
Nuclear medicine imaging with iodine-123 (123I) MIBG-single-photon emission 
computed tomography (SPECT) or MIBG-SPECT/CT will be used to inform 
measurable lesions and assess primary and metastatic soft tissue and 
osteomedullary lesion response in participants with MIBG-avid tumours. 
• 
[18F] fluorodeoxyglucose (FDG) –positron emission tomography (PET) will be 
used as an alternative modality for tumour detection in participants whose tumours 
do not concentrate MIBG. 
Note: The same diagnostic method, including use of contrast when applicable, must be 
used throughout the study to evaluate disease. (eg. CT and/or MRI plus MIBG-SPECT, 
or CT and/or MRI plus FDG-PET) 
• 
Bilateral bone marrow aspirates and trephine biopsies for assessment of marrow 
disease using morphologic criteria in conjunction with appropriate antibodies to 
confirm the identity of neuroblastoma cells by immunocytology (if available) 
and/or immunohistochemistry at screening/baseline and to evaluate response 
during treatment, if positive at baseline. 
Guidelines for Evaluation of Disease 
Primary and Metastatic Soft Tissue Disease 
MIBG-SPECT/CT (or FDG-PET/CT, if tumour is MIBG-nonavid) in conjunction with 
CT/MRI should be used to evaluate soft tissue lesions. 
Target lesions: Disease sites that meet criteria of measurable size (nonlymphoid soft 
tissue mass ≥10 mm in longest dimension or lymph node ≥15mm in short axis) as well as 
either uptake on MIBG (or FDG for MIBG non-avid tumours) or biopsy positive for 
neuroblastoma or ganglioneuroblastoma. 
Non-target lesions: Lesions that are considered to be active tumour sites but do not meet 
target lesion criteria; include leptomeningeal tumour; tumour in cerebrospinal fluid, 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 149 of 213 
ascites, or pleural effusion, and lesions smaller than 10 mm that are considered likely to 
be active tumour based on clinical correlation (eg, hepatic and pulmonary nodules); small 
(<10 mm) soft tissue lesions and lymph nodes that measure shorter than 15 mm on short 
axis will be considered non-target lesions if they are biopsied and proven to consist of 
viable tumour. 
Note: Non-lymph node soft tissue lesions at least 10 mm in diameter and lymph nodes 
larger than 15 mm on short axis that are not MIBG or FDG-avid and do not contain 
viable tumour (if biopsied) will not be considered either target or non-target lesions. 
Metastatic Bone Disease:  
Osteomedullary lesions should be evaluated using MIBG-SPECT/CT imaging, or FDG-
PET/CT for participants with MIBG non-avid disease. Anatomic imaging will not be 
used to evaluate osteomedullary lesions. 
MIBG semiquantitative scoring systems will be used for response assessment in bone 
lesions with 123I-MIBG uptake. Relative score on bone sectors should be used for 
response assessment (absolute score of bone lesions at time of assessment divided by 
absolute score of bone lesions at screening/baseline).  
The same scoring method [eg, Curie (Matthay, 2003), International Society of Pediatric 
Oncology European Neuroblastoma (SIOPEN) (Ady, 1995)] and the same imaging 
modality (MIBG-SPECT, or FDG-PET for participants with MIBG non-avid disease) 
should be used for all evaluations. 
Note: Extramedullary soft tissue components of bone lesions should be assessed 
following guidance for other soft tissue sites. 
Metastatic Bone Marrow Disease: 
All sites of bone marrow involvement, including level of involvement (percentage of 
tumour infiltration of bone marrow space assessed by histologic evaluation of trephine or 
biopsy or counting of the number of tumour cells in aspirates divided by the number of 
haematopoietic or mononuclear cells evaluated to obtain a percentage of involvement) 
should be reported. 
In the case of discrepant results between aspirations or core biopsies from 2 or more sites 
taken at the same time, the highest infiltration result should be reported. 
Response Criteria 
Evaluation of Primary (Soft Tissue) Tumour Response:  
Criteria for response in primary tumour using anatomic + MIBG (FDG-PET) imaging are 
provided in Table 19. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 150 of 213 
Table 19: 
Primary (Soft Tissue) Tumour Response a 
Response 
Definition 
CR 
<10mm residual soft tissue at primary site and complete resolution of MIBG or 
FDG uptake at primary site 
PR 
≥30% decrease in longest diameter of primary site and MIBG or FDG uptake at 
primary site stable, improved, or resolved 
SD 
Neither sufficient shrinkage for PR nor sufficient increase for PD at the primary 
site 
PD 
>20% increase in longest diameter taking as reference the smallest sum on study 
(including baseline sum) and minimum absolute increase of 5mm in longest 
diameter b 
Abbreviations: CR=complete response; FDG=[18F]fluorodeoxyglucose; MIBG = metaiodobenzylguanidine; 
PD=progressive disease; PET=positron emission tomography; PR=partial response; SD=stable disease. 
a. 
Not for use in assessment of metastatic sites. 
b. 
Mass that does not meet PD measurement criteria but has fluctuating MIBG avidity will not be considered PD. 
Evaluation of Tumour Response at Metastatic Soft Tissue and Bone Sites 
Criteria for response in soft tissue (including lymph node and non-lymph node) and bone 
metastases using anatomic + MIBG (FDG) imaging are provided in Table 20. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 151 of 213 
Table 20: 
Tumour Response at Metastatic Soft Tissue and Bone Sites 
Response 
Definition 
CR 
Resolution of all sites of disease, defined as: 
• 
Nonprimary target and non-target lesions measure <10 mm AND 
• 
Lymph nodes identified as target lesions decrease to a short axis <10 mm 
AND 
• 
MIBG uptake or FDG uptake (for MIBG-nonavid tumours) of nonprimary 
lesions resolves completely 
PR 
≥30% decrease in sum of diametersa of nonprimary target lesions compared with 
baseline AND all of the following: 
• 
Non-target lesions may be stable or smaller in size  
• 
No new lesions  
• 
≥50% reduction in MIBG absolute bone score (relative MIBG bone score 
≥0.1 to <0.5) or ≥50% reduction in number of FDG-avid bone lesions b, c 
SD 
Neither sufficient shrinkage for PR nor sufficient increase for PD of nonprimary 
lesions 
PD 
Any of the following: 
• 
Any new soft tissue lesion detected by CT/MRI that is also MIBG-avid or 
FDG-avid 
• 
Any new soft tissue lesions detected by CT/MRI that has been biopsied 
and confirmed to be neuroblastoma or ganglioneuroblastoma 
• 
Any new bone site that is MIBG-avid 
• 
A new bone site that is FDG-avid (for MIBG-nonavid tumours) AND has 
CT/MRI findings consistent with tumour OR has been confirmed 
histologically to be neuroblastoma or ganglioneuroblastoma 
• 
>20% increase in longest diameter taking as reference the smallest sum on 
study (including baseline sum) and minimum absolute increase of 5mm in 
sum of longest diameters of target soft tissue lesions 
• 
Relative MIBG score >1.2 c 
Abbreviations: CR=complete response; FDG=[18F]fluorodeoxyglucose; MIBG= metaiodobenzylguanidine; 
PD=progressive disease; PET=positron emission tomography; PR=partial response; SD=stable disease; 
CT=computed tomography; MRI= magnetic resonance imaging. 
a. 
Sum of diameters is defined as the sum of the short axis of discrete lymph nodes (ie, cervical, axillary nodes) 
added to the sum of the longest diameters of non-lymph node soft tissue metastases. Masses of conglomerate 
nondiscrete lymph nodes will be measured using longest diameter. 
b. 
For participants with soft tissue metastatic disease, resolution of MIBG and/or FDG uptake at the soft tissue 
sites is not required; all size reduction criteria must be fulfilled. 
c. 
Relative MIBG score is the absolute score for bone lesions at time of response assessment divided by the 
absolute score for bone lesions at baseline before therapeutic interventions. The same scoring method (eg, 
Curie or SIOPEN) must be used at all assessment time points 
Evaluation of Metastatic Bone Marrow Disease 
Criteria for response in bone marrow metastasis using cytology/histology are provided in 
Table 21. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 152 of 213 
Table 21: 
Metastatic Bone Marrow Disease 
Response 
Definition (Cytology†/Histology‡) 
CR 
Bone marrow with no tumour infiltration on reassessment, independent of 
baseline tumour involvement 
PR 
Any of the following: 
• 
Bone marrow with ≤5% tumour infiltration and remains > 0 to ≤ 
5% tumour infiltration on reassessment 
• 
Bone marrow with no tumour infiltration that has ≤ 5% tumour 
infiltration on reassessment  
• 
Bone marrow with >20% tumour infiltration that has > 0 to ≤ 5% 
tumour infiltration on reassessment 
SD 
Bone marrow with tumour infiltration that remains positive with > 5% tumour 
infiltration on reassessment but does not meet CR, MD, or PD criteria 
PD 
Any of the following: 
• 
Bone marrow without tumour infiltration that becomes > 5% 
tumour infiltration on reassessment 
• 
Bone marrow with tumour infiltration that increases by > two-fold 
and has >20% tumour infiltration on reassessment 
Abbreviations: CR=complete response; PD=progressive disease; PR=partial response; SD=stable disease; 
MD=minimal disease. 
†Accompanied by immunocytology (recommended, not mandatory). 
‡Accompanied by immunohistochemistry, specific recommendations included in article by Burchill, 2016. 
Evaluation of Overall Response 
Table 22 presents potential overall responses for all possible combinations of tumour 
responses in primary soft tissue, metastatic soft tissue and bone sites, and metastatic bone 
marrow disease. 
Table 22: 
Evaluation of Overall Response 
Response 
Criterion 
CR 
All components meet criteria for CR 
PR 
PR in at least one component and all other components are either CR, MD* (bone 
marrow), PR (soft tissue or bone), or NI†; no component with PD 
MR 
PR or CR in at least one component but at least one other component with SD; no 
component with PD 
SD 
SD in one component with no better than SD or NI† in any other component; no 
component with PD 
PD 
Any component with PD 
Abbreviations: CR=complete response; PD=progressive disease; PR=partial response; SD=stable disease; 
MR=minor response. 
*For bone marrow assessment only. 
†Site not involved at study entry and remains uninvolved. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 153 of 213 
Confirmation Criteria 
To be assigned a status of confirmed PR or CR, a confirmatory disease assessment should 
be performed no less than 4 weeks (28 days) after the criteria for response are first met. 
Please refer to the Tumour Assessment Flowchart (Table 4) for information on imaging 
requirements for response confirmation. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 154 of 213 
APPENDIX 6. LIST OF ABBREVIATIONS AND DEFINITIONS OF 
TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
Table 23: 
Abbreviations and Specialist Terms  
Abbreviation or Specialist Term 
Explanation 
ADA(s) 
antidrug antibody(ies) 
ADR 
adverse drug reaction 
AE 
adverse event 
AESI 
adverse event of special interest 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AML 
acute myeloid leukaemia 
API 
Active pharmaceutical ingredient 
aPTT 
Activated partial thromboplastin time 
ASCO 
American Society of Clinical Oncology 
AST 
aspartate aminotransferase 
AUC 
area under the plasma concentration-time curve 
BLA 
Biologics License Application 
BOR 
best overall response 
CBC 
complete blood count 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CL 
clearance 
Cmax 
maximum plasma concentration 
Cmin 
minimum plasma concentration 
CMAA 
Conditional Marketing Authorisation Application 
CNS 
central nervous system 
COVID-19 
Coronavirus Disease 2019 
CO2 
Carbon dioxide 
CR 
complete response 
CRF 
case report form 
CRO 
contract research organisation 
CSR 
clinical study report 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 155 of 213 
Abbreviation or Specialist Term 
Explanation 
CTR 
Clinical Trials Regulations 
CV 
coefficient of variation 
CYP 
cytochrome P450 enzyme 
DCR 
disease control rate 
DEC 
Dose Escalation Committee 
DL-1 
dose level -1 
DL1 
dose level 1 
DL2 
dose level 2 
DLT 
dose limiting toxicity 
DRC 
Data Review Committee 
DRESS 
Drug reaction with eosinophilia and systemic symptoms 
dMMR 
mismatch repair-deficient 
DOR 
duration of response 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EMA 
European Medicines Agency 
EOT 
End of Treatment 
EU 
European union 
FDA 
Food and Drug Administration 
FDG-PET/CT 
fluorodeoxyglucose-positron emission 
tomography/computed tomography 
FSH 
follicle-stimulating hormone 
FT3 
free triiodothyronine 
FT4 
free thyroxine 
GCP 
Good Clinical Practice 
G-CSF 
granulocyte-colony stimulating factor 
HbcAB 
hepatitis B core antibody,  
HBsAg  
hepatitis B surface antigen;  
HBV 
HBV = hepatitis B virus;  
HCV 
HCV=hepatitis C virus; 
HR 
hazard ratio 
HRT 
hormonal replacement therapy 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
ICI 
immune checkpoint inhibitor 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 156 of 213 
Abbreviation or Specialist Term 
Explanation 
IEC 
Independent Ethics Committee 
IgG4 
immunoglobulin G4 
INRC 
International Neuroblastoma Response Criteria 
imAE 
immune-mediated adverse event 
imAEI 
immune-mediated adverse event of interest 
IRB 
Institutional Review Board 
IRR 
Infusion-related reactions 
IV 
intravenous 
K 
Potassium 
LAR 
legally authorised representative 
mAb 
monoclonal antibody 
MATE 
multidrug and toxin extrusion transporter 
MDS 
myelodysplastic syndrome 
MedDRA 
Medical Dictionary for Regulatory Activities 
MIBG-SPECT/CT 
metaiodobenzylguanidine-single-photon emission 
computed tomography/computed tomography 
mITT 
modified intent-to-treat 
MRI 
magnetic resonance imaging 
MSI-H 
high microsatellite instability 
MTD 
maximum tolerated dose 
mTPI 
modified toxicity probability interval 
mTPI-2 
modified toxicity probability interval-2 
Na 
Sodium 
NAb 
neutralising antibody(ies) 
NCI 
National Cancer Institute 
NE 
not evaluable 
NIH 
National Institutes of Health 
NSAIDS 
Nonsteroidal anti-inflammatory drugs 
ORR 
objective response rate 
PARP 
poly (adenosine diphosphate-ribose) polymerase 
PD 
progressive disease 
PD-1 
programmed cell death protein 1 
PD-L1 
programmed cell death-ligand 1 
PD-L2 
programmed cell death-ligand 2 
PET 
positron emission tomography 
PFS 
progression-free survival 
PFS6 
progression-free survival rate at 6 months 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 157 of 213 
Abbreviation or Specialist Term 
Explanation 
PK 
pharmacokinetic(s) 
PR 
partial response 
PRES 
Posterior Reversible Encephalopathy Syndrome 
PT 
prothrombin time 
PTT 
partial thromboplastin time 
Q3W 
every 3 weeks 
Q6W 
every 6 weeks 
QTcB 
QT interval corrected for heart rate according to Bazett’s 
formula 
QTcF 
QT interval corrected for heart rate according to 
Fridericia’s formula 
QTL 
quality tolerance limit 
RECIST 
Response Evaluation Criteria in Solid Tumours 
RP2D 
recommended Phase 2 dose 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
stable disease 
SJS 
Stevens-Johnson Syndrome 
SoA 
schedule of activities 
SPECT 
single-photon emission computed tomography 
STING 
stimulator of interferon genes 
t½ 
half-life 
T3 
triiodothyronine 
TEAE 
treatment-emergent adverse event 
TEN 
toxic epidermal necrolysis 
TfOS 
tablet for oral suspension 
tmax 
time to maximum plasma concentration 
TSH 
thyroid-stimulating hormone 
ULN 
upper limit of normal 
UPM 
unit probability mass 
US 
United States of America 
WHO 
Word health organisation 
WMA 
World Medical Association 
WOCBP 
woman of childbearing potential 
 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 158 of 213 
Definition of Terms 
Term 
Definitions 
Adverse Drug 
Reaction (ADR) 
An AEs where a causal relationship between a medicinal product and 
the AEs is at least a reasonable possibility, i.e., the relationship 
cannot be ruled out. 
a. 
In the context of a clinical trial, an ADR can be serious or 
nonserious. Serious ADRs may be subject to expedited reporting 
if they are considered unexpected (see SUSAR definition). 
b. 
For marketed products, ADRs are subject to expedited reporting 
within the country where they are authorised. 
AxMP 
Medicinal products used in the context of a clinical trial but not as 
IMPs, such as medicinal products used for background treatment, 
challenge agents, rescue medication, or used to assess endpoints in a 
clinical trial. AxMPs should not include concomitant medications, 
i.e., medications unrelated to the clinical trial and not relevant for the 
design of the clinical trial. 
Authorised AxMP = Medicinal product authorised in accordance with 
Regulation (EC) No 726/2004, or in any member state concerned in 
accordance with Directive 2001/83/EC, irrespective of changes to the 
labelling of the medicinal product. 
Note: Safety reporting with regard to authorised AxMPs shall be 
made in accordance with Chapter 3 of Title IX of Directive 
2001/83/EC. 
Unauthorised AxMP = Medicinal product not authorised in 
accordance with Regulation (EC) No 726/2004 
Safety reporting for unauthorised AxMPs will follow the same 
processes and procedures as SUSAR safety reporting. 
Co-administered 
(concomitant) 
products 
A product given to clinical trial participants as required in the 
protocol as part of their standard care for a condition which is not the 
indication for which the IMP is being tested and is therefore not part 
of the objective of the study. 
Investigational 
Product 
A pharmaceutical form of an active substance or placebo being tested 
or used as a reference in a clinical trial, including products already 
with a marketing authorisation but used or assembled (formulated or 
packaged) in a way different from the authorised form, or when used 
for an unauthorised indication, or when used to gain further 
information about the authorised form. 
Legal guardian 
Parent(s) (preferably both if available or as per local requirements), 
legally appointed guardian(s), or LARs, as defined by national and 
local laws and regulations, who consent(s) on behalf of the minor. 
For the purposes of this study, all references to informed consent and 
assent refer to the paediatric participant (child) and his or her legal 
guardian who have provided consent (and assent as applicable), 
according to the Informed Consent Process and Assent form 
described in the Informed Consent Process section. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 159 of 213 
Term 
Definitions 
NIMP 
A NIMP is a medicinal product that is not classified as an IMP in a 
study, but may be taken by participants during the study, e.g., 
concomitant or rescue/escape medication used for preventive, 
diagnostic, or therapeutic reasons or medication given to ensure that 
adequate medical care is provided for the participant during a study. 
Paediatric participant 
Minor child participating in research study. 
Rescue medication 
Medicines identified in the protocol as those that may be 
administered to the participants when the efficacy of the IMP is not 
satisfactory, or the effect of the IMP is too great and is likely to cause 
a hazard to the patient, or to manage an emergency situation. 
Serious Adverse 
Reaction 
All noxious and unintended responses to an IMP related to any dose 
administered that result in death, are life-threatening, require patient 
hospitalisation or prolongation of existing hospitalisation, result in 
persistent or significant disability or incapacity, or are a congenital 
anomaly or birth defect. 
Suspected unexpected 
serious adverse 
reaction 
A suspected unexpected serious adverse reaction is a serious adverse 
reaction whose nature, severity or outcome is not consistent with the 
reference safety information. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 160 of 213 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 161 of 213 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 162 of 213 
APPENDIX 8. LIVER SAFETY: REQUIRED ACTIONS, 
MONITORING, AND FOLLOW-UP TO ASSESS 
CAUSALITY OF LIVER EVENT 
Phase I/II liver chemistry stopping and increased monitoring criteria have been 
designed to assure participant safety and evaluate liver event etiology (in alignment with 
the FDA premarketing clinical liver safety guidance). 
Table 24: 
Required actions, monitoring, and follow-up to assess causality of 
liver event 
Liver event study intervention stopping criteria 
ALT absolute 
Both ALT 5xULN and 2x baseline value 
ALT increase 
Unable to monitor weekly for 4 weeks: 
Both ALT 3xULN and 1.5x baseline value  
Able to monitor weekly: 
Both ALT 3xULN and 1.5x baseline value that persists for 4 weeks. 
Note: if values reduce to 3xULN and 1.5 x baseline or return to within baseline or 
normal limits for 2 consecutive weekly assessment, weekly monitoring may return to 
regular per protocol schedule. 
Bilirubin1, 2 
ALT 3xULN and total bilirubin 2xULN (for participants with known Gilbert’s syndrome 
these criteria only apply if total bilirubin 2xULN, and direct bilirubin 2xULN and at 
least doubled from baseline value). 
INR2 
ALT 3xULN and INR 1.5 
Symptomatic3 
Both ALT 3xULN and 1.5x baseline value associated with symptoms (new or 
worsening) believed to be related to liver injury or hypersensitivity. 
Required actions, monitoring and follow-up to assess causality of liver event 
Actions and monitoring 
Follow-up to assess causality of liver event 
• 
Immediately discontinue study intervention. 
• 
Report the event to GSK within 24 hours. 
• 
Complete the liver event form and complete SAE 
data collection tool if the event also meets the 
criteria for an SAE2. 
• 
Perform liver event follow-up to assess causality of 
liver event. 
• 
Monitor the participant liver chemistries (see 
MONITORING). 
 
MONITORING: 
If ALT 3xULN AND total bilirubin 2xULN or INR 1.5: 
• 
Repeat liver chemistries (include ALT, AST, alkaline 
phosphatase, total bilirubin and INR) and perform 
liver event follow-up to assess liver event causality 
within 24 hours. 
• 
Monitor participants twice weekly until liver 
chemistries reduce to 3xULN for ALT, 2xULN for 
total bilirubin or1.5 for INR or return to or remain 
within baseline or normal limits. 
• 
A specialist or hepatology consultation is 
recommended. 
• 
Viral serology4. 
• 
Anti-nuclear antibody, anti-smooth muscle 
antibody, Type 1 anti-liver kidney microsomal 
antibodies, and quantitative total IgG (IgG or 
gamma globulins). 
• 
Blood and serum sample for PK analysis of 
niraparib and dostarlimab, respectively, 
obtained within 144 hours after last dose of 
study intervention5. 
• 
Serum CPK and LDH, GGT, GLDH, and serum 
albumin. 
• 
Fractionate bilirubin, if total bilirubin 2xULN. 
• 
Obtain complete blood count with differential to 
assess eosinophilia. 
• 
Record the appearance or worsening of clinical 
symptoms of liver injury, or hypersensitivity, on 
the liver event form. 
• 
Record use of concomitant medications on the 
concomitant medications report form including 
acetaminophen, herbal remedies, recreational 
drugs and other over the counter medications. 
• 
Record alcohol use on the liver event alcohol 
intake form. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 163 of 213 
For all other criteria (total bilirubin 2xULN and INR 
1.5): 
• 
Repeat liver chemistries (include ALT, AST, alkaline 
phosphatase, total bilirubin and INR) and perform 
liver event follow-up to assess liver event causality 
within 24-72 hours. 
• 
Monitor participants weekly until liver chemistries 
reduce to 3xULN for ALT or return to or remain 
within baseline or normal limits. 
RESTART and/or RECHALLENGE 
• 
Restart and/or rechallenge is allowed per protocol 
but do not resume study intervention unless GSK 
approval is granted. If restart and/or rechallenge is 
not granted, permanently discontinue study 
intervention and continue participant in the study for 
any protocol-specified follow-up assessments. Refer 
to Restart and/or Rechallenge guidelines in 
Appendix 9. 
If ALT 3xULN AND total bilirubin 2xULN or INR 
1.5 obtain the following in addition to the 
assessments listed above: 
• 
Serum acetaminophen adduct assay should be 
conducted (where available) to assess potential 
acetaminophen contribution to liver injury. 
• 
Liver imaging (ultrasound, magnetic resonance, 
or computed tomography) to evaluate liver 
disease, complete liver imaging form. 
• 
Liver biopsy may be considered and discussed 
with local specialist if available, for instance: 
– 
In patients when serology raises the 
possibility of AIH. 
– 
In patients when suspected DILI 
progresses or fails to resolve on withdrawal 
of study intervention. 
– 
In patients with acute or chronic atypical 
presentation. 
• 
If liver biopsy conducted, then complete liver 
biopsy form. 
AIH = Autoimmune hepatitis; ALT = Alanine aminotransferase; AST = Aspartate aminotransferase; CPK = Creatine 
phosphokinase; CRF = Case report form; DNA = Deoxyribonucleic acid; DILI = Drug-induced liver injury; GGT = 
Gamma glutamyl transferase; GLDH = Glutamate dehydrogenase; HBcAb = Hepatitis B core antibody; HBsAg = 
Hepatitis B surface antigen; HBV = Hepatitis B virus; HDV = Hepatitis D virus; IgG = Immunoglobulin G; IgM = 
Immunoglobulin M; INR = International normalised ratio; LDH = Lactate dehydrogenase; PCR = Polymerase chain 
reaction; PK = Pharmacokinetic; RNA = Ribonucleic acid; SAE = Serious adverse event; ULN = Upper limit of normal. 
1. 
Serum bilirubin fractionation should be performed if testing is available. Additionally, if serum bilirubin fractionation 
testing is unavailable, record presence of detectable urinary bilirubin on dipstick, indicating direct bilirubin 
elevations and suggesting liver injury. 
2. 
All events of ALT 3xULN and total bilirubin 2xULN (for participants with known Gilbert’s syndrome these criteria 
only apply if total bilirubin 2xULN, and direct bilirubin 2xULN and at least doubled from baseline value) or ALT 
3xULN and INR 1.5, which may indicate severe liver injury (possible ‘Hy’s Law’), must be reported as an SAE 
(excluding studies of hepatic impairment or cirrhosis); the INR threshold value stated will not apply to participants 
receiving anticoagulants. 
3. 
New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, or jaundice) or believed to be related to hypersensitivity (such as fever, rash or 
eosinophilia). 
4. 
Includes: Hepatitis A IgM antibody; HBsAg and HBcAb (IgM); Hepatitis C RNA; Cytomegalovirus IgM antibody; 
Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, obtain heterophile antibody or monospot testing); 
Hepatitis E IgM antibody and RNA PCR test. HBV DNA quantification, and HDV antibody should be measured if 
participant known to be HBsAg and/or HBcAb positive prior to onset of the liver event or subsequently found to be 
HBsAg positive on investigation following the liver event. If hepatitis delta antibody assay cannot be performed, it 
can be replaced with a PCR of hepatitis D RNA virus (where needed and if this is feasible). 
5. 
Record the date/time of the PK blood sample draw and the date/time of the last dose of study intervention prior to 
blood or serum sample draw on the CRF. If the date or time of the last dose is unclear, provide the participant’s 
best approximation. If the date/time of the last dose cannot be approximated OR a PK sample cannot be collected 
in the time period indicated above, do not obtain a PK sample. Instructions for sample handling and shipping are 
in the Laboratory Manual. 
 
 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 164 of 213 
Table 25: 
Liver Safety: Liver Chemistry Increased Monitoring Criteria with 
Continued Therapy 
Liver Chemistry Increased Monitoring Criteria and Actions with Continued Study 
Treatment – Liver Monitoring Event 
Criteria 
Actions 
• ALT ≥3×ULN and ≥ 1.5x baseline 
value and not meeting stopping criteria, 
without symptoms believed to be 
related to liver injury or 
hypersensitivity and who can be 
monitored weekly for 4 weeks. 
• Notify the GSK Medical Monitor within 24 
hours of learning of the abnormality to 
discuss participant safety.  
• Participant can continue study treatment. 
• Participant must return weekly for repeat liver 
chemistries (ALT, AST, ALP, total bilirubin, 
and INR) until they stabilise until they 
stabilise (i.e., ALT or AST <3xULN and 
<1.5x baseline, and no increases in total 
bilirubin and INR) or return or remain to 
within baseline or normal limits. 
• If at any time participant meets the liver 
chemistry stopping criteria, proceed as 
described above. 
• If, after 4 weeks of monitoring, stopping 
criteria have not been met but any of the 
monitored liver chemistry (ALT, AST, 
alkaline phosphatase, total bilirubin and INR) 
remains abnormal/above baseline, monitor 
participants twice monthly until they stabilise 
or return to within baseline or normal limits. 
Alternatively, the monitoring can return to 
standard as per protocol when the Investigator 
and Medical Monitor agree that values are 
stable or no longer significantly abnormal 
(this may require local investigation of 
potential causes for liver chemistry 
abnormality). 
Abbreviations: ALT=alanine aminotransferase; AST=aspartate aminotransferase; GSK= GlaxoSmithKline; 
INR = International normalised ratio; ULN=upper limit of normal 
 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 165 of 213 
APPENDIX 9. LIVER SAFETY DRUG RESTART OR 
RECHALLENGE GUIDELINES 
If participant meets liver chemistry stopping criteria do not restart/rechallenge participant 
with study treatment unless per protocol or: 
• 
GSK Medical Governance approval is granted (as described below), 
• 
Ethics and/or IRB approval is obtained, if required, and 
• 
Separate consent for treatment restart/rechallenge is signed by the participant 
If GSK Medical Governance approval to restart/rechallenge participant with study 
treatment is not granted, then participant must permanently discontinue study treatment 
and may continue in the study for protocol-specified follow-up assessments.  
Rechallenge Following Liver Stopping Events that are Possibly Related 
to Study Treatment 
Following drug-induced liver injury, drug rechallenge is associated with a 13% 
mortality across all drugs in prospective studies (Andrade, 2009). Clinical outcomes 
vary by drug, with nearly 50% fatality with halothane readministered within one month 
of initial injury. However, some drugs seldom result in recurrent liver injury or fatality. 
Risk factors for a fatal drug rechallenge outcome include: 
• 
hypersensitivity (Andrade, 2009) with initial liver injury (e.g., fever, rash, 
eosinophilia)  
• 
jaundice or bilirubin >2×ULN with initial liver injury (direct bilirubin >35% of 
total) 
• 
participant currently exhibits severe liver injury defined by: ALT >3×ULN, 
bilirubin >2×ULN (direct bilirubin >35% of total), or INR>1.5 
• 
serious adverse event or fatality has earlier been observed with drug rechallenges 
(Hunt, 2010; Papay, 2009) 
• 
evidence of drug-related preclinical liability (e.g., reactive metabolites; 
mitochondrial impairment) (Hunt, 2010) 
Rechallenge refers to resuming study treatment following drug-induced liver injury 
(DILI). Because of the risks associated with rechallenge after DILI this should only be 
considered for a participant for whom there is compelling evidence of benefit from a 
critical or life-saving medicine, there is no alternative approved medicine available, and a 
benefit:risk assessment of rechallenge is considered to be favourable. 
Approval by GSK for rechallenge with study treatment can be considered where: 
• 
Investigator requests consideration of rechallenge with study treatment for a 
participant who is receiving compelling benefit with study treatment that exceeds 
risk, and no effective alternative therapy is available. 
• 
Ethics Committee or Institutional Review Board approval for rechallenge with 
study treatment has been obtained, if required. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 166 of 213 
If the rechallenge is approved by GSK Medical Governance in writing:  
• 
The participant must be provided with a clear description of the possible benefits 
and risks of study treatment administration, including the possibility of recurrent, 
more severe liver injury or death. 
• 
The participant must also provide signed informed consent specifically for the 
rechallenge with study treatment. Documentation of informed consent must be 
recorded in the study chart. 
• 
Study treatment must be administered at the dose specified by GSK. 
• 
Participants approved by GSK Medical Governance for rechallenge with study 
treatment must return to the clinic twice a week for liver chemistry tests until 
stable liver chemistries have been demonstrated and then standard laboratory 
monitoring may resume as per protocol. 
• 
If after study treatment rechallenge, participant meets protocol-defined liver 
chemistry stopping criteria, study treatment should be permanently discontinued.  
• 
GSK Medical Monitor, and the Ethics Committee or Institutional Review Board as 
required, must be informed of the participant’s outcome following study treatment 
rechallenge.  
• 
GSK to be notified of any adverse events, as per Appendix 2. 
Restart Following Transient Resolving Liver Stopping Events Not 
Related to Study Treatment 
Restart refers to resuming study treatment following liver stopping events in which there 
is a clear underlying cause (other than DILI) of the liver event (e.g., biliary obstruction, 
pancreatic events, hypotension, acute viral hepatitis). Furthermore, restart is not permitted 
following liver stopping event when the underlying cause was alcohol-related hepatitis.  
Approval by GSK for study treatment restart can be considered where: 
• 
Investigator requests consideration for study treatment restart if liver chemistries 
have a clear underlying cause (e.g., biliary obstruction, hypotension and liver 
chemistries have improved to normal or are within 1.5×baseline and ALT 
<3×ULN). 
• 
Possible study intervention-induced liver injury has been excluded by the principal 
Investigator and the study team. This includes the absence of markers of 
hypersensitivity (otherwise unexplained fever, rash, eosinophilia). Where a study 
intervention has an identified genetic marker associated with liver injury (e.g., 
lapatinib, abacavir, amoxicillin/clavulanate), the presence of the marker should be 
excluded. If study intervention-related liver injury cannot be excluded, the 
guidance on rechallenge in Section 7.1 will apply 
• 
There is no evidence of alcohol-related hepatitis. 
• 
Ethics Committee or Institutional Review Board approval of study treatment 
restart must be obtained, as required. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 167 of 213 
If restart of study treatment is approved by GSK Medical Governance in 
writing: 
• 
The participant must be provided with a clear description of the possible benefits 
and risks of study treatment administration, including the possibility of recurrent, 
more severe liver injury or death. 
• 
The participant must also provide signed informed consent specifically for the 
study treatment restart. Documentation of informed consent must be recorded in 
the study chart. 
• 
Study treatment must be administered at the dose specified by GSK. 
• 
Participants approved by GSK Medical Governance for restarting study treatment 
must return to the clinic once a week for liver chemistry tests until stable liver 
chemistries have been demonstrated and then laboratory monitoring may resume 
as per protocol.  
• 
If after study treatment restart, participant meets protocol-defined liver chemistry 
stopping criteria, study treatment should be permanently discontinued. 
• 
GSK Medical Monitor, and the Ethics Committee or Institutional Review Board, 
must be informed of the participant’s outcome following study treatment restart.  
• 
GSK to be notified of any adverse events, as per Appendix 2. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 168 of 213 
APPENDIX 10. MTPI-2 DESIGN 
The dose escalation and de-escalation will be guided by the modified toxicity probability 
interval-2 (mTPI-2) design (Guo, 2017). The study team will use mTPI-2 spreadsheet and 
relevant pharmacokinetic information to make the final dose escalation, de-escalation, 
and appropriate dose decision for the next dose level. 
Modified toxicity probability interval (mTPI) is an interval-based Bayesian design for 
dose finding (Ji, 2013). It utilises a Bayesian model to make escalation decisions based 
on the observed dose-limiting toxicities (DLTs) from the current dose level. Extensive 
simulation studies in literature have shown that, compared to a traditional rule-based 
design like 3+3, mTPI has favourable operational characteristics. In general, mTPI can 
more accurately select the maximum tolerated dose (MTD). Meanwhile, mTPI maintains 
a similar safety profile to designs like 3+3 in that the probabilities of overdosing are 
comparable. Moreover, mTPI is as transparent as methods like 3+3 in that all the dose 
finding decisions are precalculated in a spreadsheet before the study starts. Additionally, 
mTPI has the flexibility in the number of participants to be enrolled in a dose cohort. 
In order to improve the mTPI dose finding performance in a small sample size, which is 
typically the case in a dose finding study, Guo et al developed the mTPI-2 design to 
overcome the Ockham’s razor issue in the mTPI design that may lead to undesirable dose 
finding decisions from a safety perspective. Guo et al have shown that mTPI-2 has 
improved the mTPI performance in small sample size scenarios (Guo, 2017). 
mTPI-2 Design 
In this study, the target probability of DLT is chosen as 0.3, and the proper dosing 
toxicity interval is defined as (0.3-0.04, 0.3+0.04)=(0.26, 0.34). That is, any dose with a 
true probability of DLT falling in the proper dosing interval is consider as a candidate for 
the MTD. The underdosing interval is defined as a toxicity interval of (0, 0.26). The 
overdosing interval is defined as a toxicity interval of (0.34, 1.00). In order to perform the 
mTPI-2 evaluation, the underdosing and overdosing intervals are further divided into the 
following subintervals: 
• 
underdosing subintervals: (0, 0.02), (0.02, 0.10), (0.10, 0.18), and (0.18, 0.26) 
• 
overdosing subintervals: (0.34, 0.42), (0.42, 0.50), (0.50, 0.58), (0.58, 0.66), (0.66, 
0.74), (0.74, 0.82), (0.82, 0.90), (0.90, 0.98), and (0.98, 1) 
For each dose level, an uninformative prior distribution Beta (1,1) is assigned to the 
probability of DLT. After treating participants at a given dose level and collecting DLT 
data, we use Bayesian methods to derive the posterior distribution for the probability of 
DLT. Then, for each of the proper dosing intervals, underdosing subintervals, and 
overdosing subintervals, we calculate the unit probability mass (UPM): posterior 
probability of the interval divided by the length of the interval. Then we identify the 
interval with the maximum UPM, as follows: 
• 
If the maximum UPM is from one of the underdosing subintervals, escalate the 
dose. 
• 
If the maximum UPM is from the proper dosing interval, stay on the current dose. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 169 of 213 
• 
If the maximum UPM is from one of the overdosing subintervals, de-escalate the 
dose. 
Table 26 shows the mTPI-2 decision spreadsheet based on a 0.3 target probability of 
DLT and a proper dosing toxicity interval (0.26, 0.34). The spreadsheet is produced for a 
dose cohort up to 30 participants and applies to every dose cohort. The spreadsheet was 
generated from the mTPI-2 online tool at http://www.compgenome.org/NGDF. 
Table 26: 
mTPI-2 Decision Spreadsheet 
 
Abbreviations: D=de-escalation; DLT=dose limiting toxicity; DU=unacceptable dose; E=escalation; 
mTPI-2=modified toxicity probability interval-2; S=stay at the same dose. 
 
 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 170 of 213 
 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 171 of 213 
APPENDIX 12. CONSIDERATIONS FOR PARTICIPANTS WITH 
PAST HBV INFECTION 
Management of Participants With Past HBV Infection 
• Management by an HBV specialist is required. If a participant is not currently 
followed by a specialist, care should be established at the start of the study, prior to 
the first dose. 
• Participants should be monitored for HBV reactivation according to Table 27. 
• Participants who experience clinically significant elevations in liver chemistries 
meeting liver event monitoring and/or liver stopping criteria should, in addition to 
the actions outlined in Section 7.1.1, Appendix 8, and Appendix 9 undergo immediate 
and careful evaluation of etiology including HBV DNA, HBsAg and Hepatitis D 
Virus testing. 
• Participants receiving dostarlimab who develop a dostarlimab-related adverse event 
requiring steroid treatment (Table 11) should be evaluated by an HBV specialist to 
determine whether HBV reactivation prophylaxis is required. 
 
HBV Reactivation 
• HBV reactivation in participants with past HBV infection is defined as one of the 
following: 
o HBV DNA is detectable or 
o Reverse HBsAg seroconversion occurs (reappearance of HBsAg) 
• Participants who develop HBV reactivation should: 
o Permanently discontinue study intervention, rechallenge is not permitted 
o Immediately refer to HBV specialist for urgent treatment initiation 
o Notify Medical Monitor within 24 hours 
o Repeat laboratory testing (HBV DNA, liver chemistries, INR and 
albumin) within 1-2 weeks to assess clinical course 
 
Additional Procedures for Past HBV Infection  
The procedures listed in Table 27 apply ONLY to participants in screening who have 
been enrolled and who have a past HBV infection (HBsAg negative, anti-HBcAb 
positive, HBV DNA negative); all procedures must be done as needed in addition to the 
required procedures for all participants detailed in the SoA (Section 1.3). 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 172 of 213 
Table 27: 
HBV Schedule of Activities 
HBV study 
assessments 
During Screening/ 
prior to starting 
study intervention 
Every 3 months during 
Treatment Period 
EOT 
90-day Safety Follow-
up 
HBV DNA testing 
X 
Xa 
X 
X 
HBsAg testing 
X 
Xa 
X 
X 
Abbreviations: DNA = deoxyribonucleic acid; EOT = end of treatment; HbsAg = hepatitis B surface antigen; 
HBV = hepatitis B virus 
a. 
Participants should receive testing every 3 months with other predose safety labs, or if liver chemistry elevations 
requiring increased liver monitoring or stopping criteria occur, or for any clinical suspicion of HBV reactivation. 
 
 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 173 of 213 
 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 174 of 213 
APPENDIX 14. PROTOCOL AMENDMENT HISTORY 
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the Table of Contents. 
Amendment 01 (16 October 2020) 
Overall Rationale for Amendment 01 
Amendment 01 revised the protocol requirement for tumour assessments to be aligned 
with current standard of care and provides other clarifications and editorial changes 
catalogued since the issuance of the prior version of the protocol. Additionally, minor 
changes to the time allowed for safety reporting to ensure consistency with GSK standard 
practices. Changes for Amendment 01 are shown in Table 2. 
Summary of Changes for Amendment 01 
Table 2: Summary of Changes for Amendment 01 
Section(s) Affected 
Description of Change 
Brief Rationale 
Headers, cover page, and 
Protocol Amendment 
Summary of Changes 
Headers and cover page were 
updated with new version 
number; headers were 
updated with new document 
number; Protocol 
Amendment Summary of 
Changes section was updated 
to include rationale for this 
version. 
Editorial changes to align 
with the Sponsor’s standard 
protocol template and ways 
of working and inclusion of 
specific language noted 
during Health Authority 
review 
Section 1.1. Synopsis 
Addition of cross-reference to 
study design schema 
Additional information 
included for ease of reading 
Section 1.3. Schedule of 
Activities 
Revision to footnote for vital 
signs assessment to include 
guidance for blood pressure 
monitoring  
Alignment with niraparib 
safety monitoring in 
accordance with 
Investigator’s Brochure, and 
Package Insert/Summary of 
Product Characteristics  

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 175 of 213 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 1.1. Synopsis  
Section 1.3 Schedule of 
Activities 
Table 4: Tumour Assessment 
Flowchart 
Section 4.1.3 General Study 
Conduct 
Section 8.1.2.1. Timing of 
Radiologic Evaluations 
Appendix 5. List of 
Abbreviations and 
Definitions 
Revision of preferred imaging 
types and schedule for scans; 
additionally, Schedule of 
Activities revised to separate 
imaging assessments 
according to different timings 
for standard of care and type 
of assessments 
Allowable imaging types and 
schedule revised to align with 
current standard of care 
Section 2.4. Rationale for 
Tumour Type 
Deletion of duplicated 
reference 
Typographical error 
Section 1.1 Synopsis 
Section 4.1.1. Part 1A Design  
Clarification of DLT criteria 
that facilitates dosing strategy 
by Dose Escalation 
Committee 
Clarification to align protocol 
language with expected 
design plan 
Section 4.1.2.1. Intra-
participant Dose Escalation 
Language revised to limit 
intra-participant dose 
escalation to Part 1A and 
limit escalation to one dose 
level higher 
Revision to provide more 
specific instruction  
Section 1.1. Synopsis 
Section 4.1.2. Part 1B Design 
Inclusion of language to align 
the PK exposure to the RP2D 
Addition to provide further 
clarity to determination of the 
RP2D 
Section 1.1. Synopsis 
Section 1.3 Schedule of 
Activities 
Section 4.1. Part 1 Dose 
Escalation Design 
Section 8.4. 
Pharmacokinetics, 
Immunogenicity, and 
Biomarkers 
Deletion of minimum body 
weight criteria for PK 
parameters  
Deletion of information 
inadvertently propagated 
throughout protocol in error 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 176 of 213 
Section(s) Affected 
Description of Change 
Brief Rationale 
Minimum threshold of 
performance status reduced to 
60% in Inclusion #4 
Criteria for adequate CBC 
collection result revised to 1 
week in Inclusion #5 
Minimum threshold of 
absolute neutrophil count 
reduced to ≥1,000/μL in 
Inclusion #5 
 
 
Revision to align with 
standard of care 
Revised safety monitoring 
guidance 
Section 1.1. Synopsis 
Section 8.1.3. PK Endpoints 
Section 9.3.3.3. Secondary 
Endpoints 
PK Parameters revised to 
provide more specificity to 
the modelling intended for 
use and to remove the 
specific parameters 
Revision of the information 
to more appropriately capture 
the components that will 
impact the statistics and 
remove detailed parameters 
as more appropriate within an 
analysis plan 
Section 1.1. Synopsis 
Section 8.4. 
Pharmacokinetics, 
Immunogenicity and 
Biomarkers 
Section 9.2. Analysis 
Populations 
Immunogenicity populations 
included 
Provided for clarity as to 
analysis populations intended 
to be studied 
Section 1.2. Schemas 
Section 4.1. Part 1 
Dose-Escalation Design 
Part 1A schemas revised to 
remove niraparib from PK 
assessment and footnote 
describing criteria for 
opening of cohorts added 
Greater alignment with the 
protocol-described study 
design and  
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 177 of 213 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 4.1.2.2. Dose 
Limiting Toxicity 
Section 4.4. Dose Adjustment 
Criteria 
Section 4.4.1. Dose 
Adjustment Criteria - 
Niraparib 
Inclusion of Posterior 
Reversible Encephalopathy 
Syndrome (PRES) as dose 
limiting toxicity 
Minor reorganization of 
instructions within 
subsections to overall section 
Guidance on dose 
modification for PRES added 
along with explanatory text 
Guidance on minimum 
threshold for neutrophil count 
reduced to ≥1,000/μL 
Update to align with known 
safety profile of niraparib 
 
Clarification of relevant 
safety instructions to 
minimize potential confusion 
Update to align with known 
safety profile of niraparib 
 
Update to align with revised 
safety monitoring guidance 
Section 4.7.2. General 
Guidance for Treatment 
Continuity when Participants 
are Unable to Come into the 
Clinic 
New section added 
Additional guidance to sites 
included in light of COVID-
19  
Section 6.2.3.1. 
Administration - Niraparib 
Instruction for sequencing of 
dostarlimab infusion and 
niraparib administration 
Additional clarity to 
investigative sites 
Section 6.5. Dose 
Modification Appendix 9. 
mTPI-2 Design 
Discussion of modified 
toxicity probability interval-2 
(mTPI-2) design removed 
from section and moved to 
appendix 
Better reorganization of the 
protocol to keep section 
limited to instruction on 
modification and separate 
statistical discussion  
Section 6.7.1. Rescue 
Medications 
Exception to allowable use of 
prophylactic cytokines added 
Corrects discrepant 
information within protocol 
Section 7.1. Discontinuation 
of Study Treatment 
Reorganization of 
information within section 
Addition of instruction to 
discontinue both niraparib 
and dostarlimab if either 
treatment is to be 
discontinued  
Inclusion of additional 
guidance and supporting 
evidence for procedures for 
imaging assessments 
Improved flow of information 
and additional guidance 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 178 of 213 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 1.3. Schedule of 
Activities 
Section 8.3.1. Time Period 
and Frequency for Collecting 
AE and SAE Information  
Section 8.3.5. Pregnancy 
Revision of language for 
collection of information for 
SAEs and AEs 
Initial reporting requirement 
changed from 24 hours to 1 
business day 
Removal of discrepant 
information and improved 
clarity 
Revision to align with GSK 
standards 
Section 8.3.6. Adverse Events 
of Special Interest 
Pneumonitis and 
embryofoetal toxicity 
removed  
Pneumonitis has been 
removed as the safety profile 
of niraparib has evolved  
Embryofoetal toxicity is 
captured in the Pregnancy 
section 
Abbreviations: AE=adverse event; 
; CBC=complete blood count; 
COVID-19=Coronavirus disease 2019; DLT=dose-limiting toxicity; GSK= GlaxoSmithKline; 
mTPI-2=modified toxicity probability interval-2; PK=pharmacokinetic; PRES=Posterior Reversible 
Encephalopathy Syndrome; RP2D=recommended Phase 2 dose; SAE=serious adverse event. 
 
Amendment 02 (23 November 2020) 
Overall Rationale for the Amendment 
Amendment 02 revises the protocol to include specific safety language noted during 
Health Authority review as detailed in Table 2. 
Summary of Changes for the Amendment 
Table 2: Summary of Changes for Amendment 02 
Section(s) Affected 
Description of Change 
Brief Rationale 
Headers, cover page, Protocol 
Amendment Summary of 
Changes, Appendix 10. 
Protocol Amendment History 
(new), and throughout 
Headers and cover page were 
updated with new version 
number; headers were 
updated with new document 
number; Protocol 
Amendment Summary of 
Changes section was updated 
to include rationale for this 
amendment and 
administrative information 
for prior amendment was 
moved to new Appendix 10. 
Protocol Amendment History. 
Editorial changes made 
throughout. 
Editorial changes to align 
with the Sponsor’s standard 
protocol template and ways 
of working, for conformity, 
clarity, flow, and 
typographical error 
correction, and for inclusion 
of specific language noted 
during Health Authority 
review 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 179 of 213 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 1.1. Synopsis (Part 
1A Design) 
Section 1.2. Schemas (Figure 
1: Part 1A Study Schema, A. 
Dose Escalation) 
Section 4.1.1. Part 1A Design 
(including Figure 2: Part 1A 
Study Schema, A. Dose 
Escalation) 
Clarified that Cohorts 1A and 
1B might not be opened in 
parallel 
To accurately reflect the 
study design 
Section 1.1. Synopsis 
(Dose-Limiting Toxicity) 
Section 4.1.2.2. 
Dose-Limiting Toxicity 
Clarified that a reason for a 
participant missing several 
doses of niraparib could be, 
but is not limited to, 
noncompliance 
Clarified that DLT criteria 
includes “any 
treatment-related” Grade≥2 
uveitis, eye pain, or blurred 
vision, Grade ≥2 
immune-related endocrine 
toxicity, and Grade 2 colitis 
or diarrhoea 
Noncompliance is a possible 
reason that participants do not 
receive the intended exposure 
of niraparib 
 
These specific criteria should 
be deemed treatment-related 
to be considered a DLT 
Section 1.1. Synopsis (Main 
Criteria for Inclusion) 
Section 5.1. Participant 
Inclusion Criteria 
Clarified that participants 
must not be eligible for local 
curative treatment (criterion 
1) 
Participants who are eligible 
for local curative treatment 
are not permitted in the study 
Section 1.1. Synopsis (Main 
Criteria for Exclusion)  
Section 5.2. 
Participant 
Exclusion Criteria 
Added language for exclusion 
in cases of pregnant or 
breastfeeding participants 
(criterion 9) 
Modified that a participant 
should not have received a 
live vaccine within 30 days of 
starting study treatment 
(criterion 18) (changed from 
14 days) 
Clarified that participants 
with QT interval prolongation 
>480 ms at screening are not 
eligible and no waivers are 
allowed (criterion 20) 
Participants who are pregnant 
or breastfeeding are excluded 
from the study 
Participants must not receive 
live vaccines within 30 days 
of starting study treatment 
Participants with QT interval 
prolongation >480 ms at 
screening are not eligible for 
the study 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 180 of 213 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 1.1. Synopsis 
(General Study Conduct) 
Section 4.1.3. General Study 
Conduct 
Section 7.1. Discontinuation 
of Study treatment 
Clarified that, during the 
long-term Follow-Up 
Assessment Period, follow-up 
might be conducted via a 
clinic visit or telephone 
contact 
To accurately reflect study 
conduct 
Section 1.3. Schedule of 
Activities/Table 3: Schedule 
of Activities (footnote g) 
Section 8.2.7. Vital Signs, 
Height, and Weight 
Clarified that blood pressure 
and heart rate monitoring 
which occurs weekly for the 
first 8 weeks during the 
Treatment Period is 
until/inclusive of Cycle 3 
Week 2, not Cycle 3 Week 3 
Error correction 
Section 4.4. Dose Adjustment 
Criteria 
Clarified that all treatment 
delays and discontinuations 
(ie, regardless of which study 
treatment) and reason should 
be recorded in the eCRF 
To accurately reflect study 
conduct 
Section 4.4.2. Dose 
Adjustment Criteria – 
Dostarlimab (Table 8: 
Guidelines for Treatment of 
Immune-Mediated Adverse 
Events of Interest) 
Section 6.7.1. Rescue 
Medications 
Added guidelines for the 
management of myocarditis 
as a possible imAE when 
receiving dostarlimab 
Added per Health Authority 
feedback 
Section 5.3. Lifestyle 
Considerations 
Added that participants 
should avoid exposure to 
ultraviolet light and take 
precautions when exposed to 
direct sunlight 
Added due to the fact that 
photosensitivity has been 
reported for participants 
receiving niraparib 
Section 6.7.2. Prohibited 
Medications 
Updated guidance regarding 
concomitant therapies used 
while receiving niraparib and 
dostarlimab 
Updated per Health Authority 
feedback and to align with 
current product labels 
Abbreviations: COVID-19-Coronavirus Disease 2019; DLT=dose-limiting toxicity; eCRF=electronic case 
report form; imAE=immune-mediated adverse event; PRES=Posterior Reversible Encephalopathy 
Syndrome; UK=United Kingdom. 
Amendment 03 (20 July 2022) 
Overall Rationale for Amendment 03: 
• 
To update safety guidance, particularly with respect to MDS/AML information. 
• 
To include new appendix for International Neuroblastoma Response Criteria 
(INRC). 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 181 of 213 
• 
To add benefit risk assessment section based on clinical studies of niraparib and 
dostarlimab. 
• 
 
. 
• 
To update inclusion and exclusion criteria. 
• 
To increase clarity and/or remove discrepancies. 
All changes are listed in Table 2. 
Table 2: 
Summary of Changes for Amendment 03 
Section(s) Affected 
Description of Change 
Brief Rationale 
Headers, title page, Protocol 
Amendment Summary of 
Changes, Appendix 12. 
Protocol Amendment 
History, and throughout 
Headers and cover page were 
updated with new version 
number; headers were updated 
with new document number; 
Protocol Amendment 
Summary of Changes section 
was updated to include 
rationale for this amendment 
and administrative 
information for prior 
amendment was moved to 
Appendix 12. Protocol 
Amendment History. Editorial 
changes made throughout. 
Editorial changes to align 
with the Sponsor’s standard 
protocol template and ways 
of working 
Title page 
Updated compound number 
“GSK4057190 to 
GSK4057190A” 
To present current correct 
compound number for 
dostarlimab 
Section 1.1 Synopsis 
(Secondary objectives) 
Section 3 Study Objectives 
and Endpoints 
Added new secondary 
objective; to assess the 
immunogenicity of 
dostarlimab in paediatric 
participants 
To correct lack of secondary 
objective given 
immunogenicity analyses are 
described in the protocol and 
an immunogenicity 
population is defined in 
Section 9 Statistical 
Considerations 
Section 1.1. Synopsis (Part 1 
Dose Escalation Design) 
Section 4.1 Part 1 Dose 
Escalation Design 
Added “DLT-evaluable” in 
advance of required numbers 
of cohort participants 
To clarify that dose 
escalation (or not) decisions 
are to be made based on data 
only from participants who 
have been determined to be 
DLT-evaluable per protocol 
definition. 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 182 of 213 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 1.1 Synopsis (Part 1A 
Design) 
Section 4.1.1: Part 1A Design 
Included language supporting 
use of 100 mg niraparib in 
participants ≥50 kg 
To provide justification 
based on results from Study 
NOVA for selection of 100 
mg niraparib dose in 
participants ≥50 kg in size 
with an option for intra-
participant dose escalation.  
Section 1.1. Synopsis (Dose 
Limiting Toxicity) 
Section 4.3 Dose Limiting 
Toxicity 
Added statement indicating 
“participant may continue on 
study treatment following a 
DLT” 
Replaced “8” with “9” in 
phrase “missed 8 or more 
doses” 
To clarify that study 
treatment is not required to 
be discontinued following a 
DLT. 
To correct error in statement. 
Participant must miss 9 or 
more doses of niraparib to 
have a dosing compliance 
value <80% over the 42-day 
DLT observation interval. 
Section 1.1. Synopsis (Dose 
Limiting Toxicity) 
Section 4.3 Dose Limiting 
Toxicity 
Added new DLT: any 
treatment-related toxicity 
resulting in reduction (for 
niraparib) or interruption of 
study treatment such that 
overall patient dosing is less 
than that required for DLT 
evaluability. 
To acknowledge role of 
treatment-related toxicities in 
overall determination of 
treatment safety. 
Section 1.1. Synopsis 
(General Study Conduct) 
Section 4.4 General Study 
Conduct 
Section 1.3. Schedule of 
Activities (Table 3 Footnote 
c) 
Section 7.1 Discontinuation 
of Study Treatment 
Clarified long-term follow-up 
assessment period 90 (±14) 
days “after the last dose of 
study treatment” 
To clearly define specific 
starting point from which to 
initiate long-term follow-up 
safety assessments 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 183 of 213 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 1.1. Synopsis 
(General Study Conduct) 
Section 4.4 General Study 
Conduct 
Added details for required 
imaging schedule for the 
period post-12 months after 
first dose of study drug 
To present a reduced scan 
schedule for participant 
monitoring that reduces 
overall radiation exposure 
and begins 12 months after 
the first dose of study drug. 
Section 1.1. Synopsis 
(General Study Conduct) 
Section 1.3. Schedule of 
Activities (Table 3 Footnote 
v) 
Section 4.4 General Study 
Conduct 
Section 8.3.1. Time Period 
and Frequency for Collecting 
AE and SAE Information 
Updated details on collection 
of AEs “or to a minimum of 
30 days after the last dose of 
study treatment if the 
participant starts subsequent 
anticancer treatment” 
To more clearly describe 
interval during which AE 
information is to be collected 
in the event of initiation of 
additional anticancer 
treatment. 
Section 1.1. Synopsis 
(Diagnosis and Main Criteria 
for Inclusion: criterion 1) 
Section 1.3: Schedule of 
Activities Table 3 Footnote e 
Section 5.1. Participant 
Inclusion Criteria (criterion 
1) 
• 
Reorganized content of 
criterion 
• 
 
 
 
 
 
 
 
• 
Replaced “prior to 
enrolment” with “prior to 
Cycle 1 Day 1” 
Section 1.1. Synopsis 
(Diagnosis and Main Criteria 
for Inclusion: criterion 1) 
Section 5.1. Participant 
Inclusion Criteria (criterion 
1) 
Moved “and must not be 
eligible for local curative 
treatment” from requirements 
for participants with tumours 
other than the specific 
tumours identified to refer to 
all participants. 
To correctly describe the 
overall participant 
population that is eligible for 
study enrolment. 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 184 of 213 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 1.1. Synopsis 
(Diagnosis and Main Criteria 
for Inclusion: criterion 3) 
Section 5.1. Participant 
Inclusion Criteria (criterion 
3) 
Added Inclusion Criterion 3 
stating requirement for 
measurable/evaluable disease 
by tumour type at time of 
study enrolment. 
To include a criterion needed 
to support enrolment of 
participants who could be 
followed for response to 
study treatment. 
Section 1.1. Synopsis 
(Diagnosis and Main Criteria 
for Inclusion: criterion 6) 
Section 5.1. Participant 
Inclusion Criteria (criterion 
6) 
Updated note describing 
timing for collection of blood 
sample for complete blood 
count 
To better describe a correct 
and more reasonable 
washout period for support 
agents (transfusion, colony-
stimulating factors, 
erythropoietin) received 
prior to collection of blood 
for complete blood count 
during screening. 
Section 1.1. Synopsis (Main 
Criteria for Exclusion: 
criterion 8)  
Section 5.2: Participant 
Exclusion Criteria (criterion 
8) 
Removed bullets on blood 
transfusion and growth factors 
in exclusion criteria 8 
To remove the guidance for 
permitted timing for 
transfusions and colony-
stimulating factor 
administration as this 
guidance has been updated in 
Inclusion criterion 6. 
Section 1.1. Synopsis (Main 
Criteria for Exclusion: 
criterion 13)  
Section 5.2: Participant 
Exclusion Criteria (criterion 
13) 
Replaced Exclusion Criterion 
13 with: Participant must not 
have a gastrointestinal 
condition, such as bowel 
obstruction, that can impact 
absorption of oral medications 
and is identified by clinical 
symptoms or CT scan, etc. 
To update exclusion criteria 
to include additional 
criterion to support 
participant safety. 
Section 1.1. Synopsis (Main 
Criteria for Exclusion: 
criterion 14)  
Section 5.2: Participant 
Exclusion Criteria (criterion 
14) 
Updated exclusion criteria 14 
to clarify guidance on 
hematologic side effects from 
prior anticancer therapy. 
To clarify information on 
excluded cytopenia 
occurrence and duration 
Section 1.1. Synopsis (Main 
Criteria for Exclusion: 
criterion 16)  
Section 5.2: Participant 
Exclusion Criteria (criterion 
16) 
Added new exclusion criteria 
“Toxicity related to prior 
immunotherapy that led to 
study treatment 
discontinuation.” 
To include guidance for 
enrolment of patients who 
had previously experienced 
toxicity in response to 
immunotherapy and to align 
eligibility requirements with 
those of dostarlimab 
protocols in general. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 185 of 213 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 1.1. Synopsis (Main 
Criteria for Exclusion: 
criterion 17)  
Section 5.2: Participant 
Exclusion Criteria (criterion 
13) 
Section 5.2: Participant 
Exclusion Criteria (criterion 
17) 
Deleted exclusion criterion 13. 
Updated exclusion criterion 
17 to clarify permitted 
window relative to first dose 
of study treatment for prior 
systemic anticancer therapy. 
Combined text from exclusion 
criterion 13 with text in 
exclusion criterion 17. 
To update permitted window 
for receipt of prior anticancer 
therapy from “within 3 
weeks” prior to first dose of 
study treatment to “within 3 
weeks or 5 half-lives, 
whichever is shorter” - a 
change which was made in 
response to an investigator’s 
suggestion, and which 
reflects half-life data for 
most common standard of 
care therapies enrolled 
patients with the specified 
tumour types.  
In addition, to make the 
excluded window consistent 
for investigational agents or 
devices and for approved 
systemic therapies of all 
types.  
Section 1.1. Synopsis (Main 
Criteria for Exclusion: 
criterion 21)  
Section 5.2: Participant 
Exclusion Criteria (criterion 
21) 
Updated exclusion criterion 
21 with corrected QTc values  
To align excluded QTc 
values with values 
appropriate for participants 
to be treated with 
dostarlimab. 
Section 1.1. Synopsis (Main 
Criteria for Exclusion: 
criterion 22)  
Section 5.2: Participant 
Exclusion Criteria (criterion 
22) 
Added exclusion criteria 22 to 
clarify that solid organ 
transplant is not permitted. 
To prohibit enrolment of 
participants who are 
receiving 
immunosuppressive therapy 
that might impact 
effectiveness of dostarlimab 
as a PD-1 inhibitor. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 186 of 213 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 1.1. Synopsis 
(Criteria for Evaluation: 
Safety) 
Added “AEs” in safety 
evaluation 
In line with study level 
requirements 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 187 of 213 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 1.3. Schedule of 
Activities (Table 3) 
Added “Post Treatment” to 
column header for FUP 
assessment Period 
To align column header 
content with text clarifying 
that Follow-up visits were to 
occur every 90 days 
following end of study 
treatment.  
Section 1.3 Table 3 Schedule 
of Activities 
Removed -10-day window 
from Screening period 
To correct outside limit of 
Screening activities window 
to -28 days rather than -28 
days + 10 additional days. 
Section 1.3 Table 3 Schedule 
of Activities 
Merged cells for EOT Visit, 
Safety FUP Visit, and FUP 
Assessment Period for the 
rows for several disease 
assessment activities  
To clarify that measures of 
disease assessment are to 
continue throughout the EOT 
and follow-up period if 
appropriate. 
Section 1.3. Schedule of 
Activities (Table 3 and 
Footnote j) 
Addition of pregnancy testing 
for WOCBP at End of 
Treatment and 30-day Safety 
Follow-up Visits 
To ensure pregnancy did not 
occur during the excluded 
period. 
Section 1.3. Schedule of 
Activities (Table 3 and 
Footnote l) 
Section 8.2.8 
Electrocardiogram 
Addition of 12-lead ECG 
testing added in Cycle 3 
In line with study level 
requirements 
Section 1.1 Synopsis, Section 
1.3 Schedule of Activities 
(Table 3 and Footnote q, r) 
Section 8.1.2.1.1 Timing and 
Considerations for Radiologic 
Assessments 
Added text indicating that 
tumour assessments should be 
conducted every 9 weeks 
(every 63 [±7] days) from the 
start of study treatment for the 
first 12 months and then every 
12 weeks (every 84 [±7] days) 
thereafter. 
To reduce total number of 
scans conducted throughout 
duration of participant 
enrolment and thereby 
reduce radiation exposure 
overall.  
Section 1.3. Schedule of 
Activities (Table 3 Footnote 
b) 
Added additional details on 
safety FUP visit 
To clarify the Safety FUP 
visit window 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 188 of 213 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 1.3 Table 3 Schedule 
of Activities Footnote k 
Section 8.2.13 Viral Disease 
Testing 
 
• 
Replaced “will’ with 
“must” in the phrase 
“Testing for hepatitis B 
surface antigen, hepatitis 
B core antibody, hepatitis 
C virus antibody, and HIV 
must be conducted where 
required by local 
Regulations or if 
warranted by participant’s 
history in accordance with 
Table 3. 
• 
 
 
 
 
 
 
To strength the guidance for 
viral disease testing during 
screening. 
 
 
 
 
 
 
 
 
 
 
 
  
Section 1.3 Schedule of 
Activities (Table 3 Footnote 
m)  
Section 8.1.2.1.1 Timing and 
Considerations for Radiologic 
Assessments 
Removed the language that 
“MRI should only be used if 
clinically appropriate, when 
CT is contraindicated, and 
preferably for imaging of the 
brain” 
To remove restrictions to use 
of MRI in medically 
appropriate scanning 
situations  
Section 1.3. Schedule of 
Activities (Table 3 Footnote 
i) 
Section 8.2.12: Laboratory 
Assessments 
Updated to replace baseline 
with “Cycle 1 Day 1” and to 
clarify guidance for Cycle 1 
Day 1 sample collection. 
To clarify that if the 
screening laboratory samples 
were collected within 7 days 
of Cycle 1 Day 1, then 
collection of these samples 
did not need to be repeated 
for Cycle 1 Day 1. 
Section 1.3. Schedule of 
Activities (Table 3 Footnote 
w, x and z) 
Updated information for 
dostarlimab PK, ADA, 
neutralising antibodies, and 
biomarker sample collection 
To provide additional 
guidance for procedures and 
timing of dostarlimab PK, 
ADA, neutralising 
antibodies, and biomarker 
sampling. 
Section 2.1.1. Clinical Data 
Updated the background on 
Niraparib marketing 
application status 
To describe that niraparib 
has been approved as 
maintenance treatment for 
patients with advanced or 
recurrent gynaecologic 
cancers. 
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 189 of 213 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 2.2.1. Clinical Data 
Updated the background on 
Dostarlimab marketing 
application status 
To describe that dostarlimab 
is approved for the treatment 
of adult patients with 
mismatch repair deficient 
(dMMR) recurrent or 
advanced endometrial 
cancer. 
Section 2.6 Benefits and 
Risks Assessment 
Substantial new sections 
added summarizing the 
overall benefit/risk of the 
study 
To align protocol structure 
with that of GSK standard 
protocol template and to 
incorporate risk/benefit 
language to meet protocol 
content requirements as 
outlined in GCP E6(R2) 
(EMA / CHMP / ICH /135 
/1995) sections 6.2.3. and 
6.2.4.). 
Section 3 Study Objectives 
and Endpoints 
Revised PK endpoint 
To describe the parameters 
constituting the endpoint 
measures. 
Section 4. Overall design 
Transferred paragraph on 
review of safety and PK data 
from Section 8.4 
Pharmacokinetics, 
Immunogenicity and 
Biomarkers 
To provide clarity on process 
for review of safety and PK 
data and role in RP2D 
determination 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 190 of 213 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 4.7.1 Niraparib; 
Table 11 (Niraparib Dose 
Modifications for 
Haematologic Adverse 
Reactions) 
Added MDS/AML language  
To describe laboratory 
assessments that must be 
conducted if MDS/AML is 
suspected 
• 
Added “unless a 
discussion with the 
Sponsor’s Medical 
Monitor has occurred” 
added to statement about 
niraparib dose-re-
escalation following a 
dose reduction.” 
• 
Updated required 
neutrophil count recovery 
level from 1000/µL to 
1500/µL. 
 
 
 
 
 
To clarify conditions under 
which niraparib dose may be 
re-escalated following dose 
reduction. 
 
To align dose modification 
guidance for neutropenia 
with that in niraparib United 
States prescribing 
information (March 2021). 
Section 4.7.2 Dose 
Adjustment Criteria for 
Dostarlimab and Section 
6.7.1 Rescue Medication  
• 
Transferred text details on 
guidance by type of 
immune-related AE from 
Section 6.7.1 Rescue 
Medication to Table 12: 
Guideline for treatment of 
Immune-Related Adverse 
Events 
• 
Table 12 updated 
• 
Changed the term 
“adverse reaction” to 
“adverse event” 
• 
Added guidance (text and 
Table 13) for infusion 
reactions. 
To combine management 
guidance for immune-related 
AEs in one location – Table 
12. 
Table 12 was updated in 
multiple areas to reflect most 
up-to-date guidance for 
management of AE 
accompanying treatment 
with dostarlimab. 
To provide appropriate 
guidance for management of 
reactions associated with 
dostarlimab infusion. 
Section 6.2.3.2 Dostarlimab  
Added text describing 
recommended post-infusion 
observation period for 
dostarlimab infusion. 
To provide additional 
guidance for participant 
safety monitoring following 
infusion of dostarlimab 
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 191 of 213 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 6.4 Study Treatment 
Compliance 
Additional content added on 
dosing diary 
To clarify completion of 
dosing diary is mandatory 
for the first two cycles and to 
align protocol content with 
that in the study pharmacy 
manual 
Section 7.1. Discontinuation 
of Study Treatment 
Removed the option for 
participants to continue 
treatment beyond confirmed 
disease progression, and 
added the requirement to 
discuss with participant’s 
legal guardian treatment 
beyond radiological evidence 
of disease progression (prior 
to confirmed disease 
progression) 
Addition of reasons for 
discontinuing treatment: 
•MDS/AML (as confirmed by 
a hematologist)  
•Secondary malignancies 
other than MDS/AML may 
require discontinuation to be 
assessed by the treating 
physician in agreement with 
the Sponsor. 
•Hypertensive crisis / PRES 
To clarify that treatment 
beyond confirmed disease 
progression is not permitted. 
 
 
 
 
 
 
 
To provide additional 
reasons based on new safety 
data that would require 
treatment discontinuation. 
Section 7.1.1 Liver 
Chemistry Stopping Criteria  
Appendix 8 Liver Safety: 
Required Actions and 
Follow-up Assessments 
Appendix 9 Liver Safety 
Drug Restart or Rechallenge 
Guidelines 
Updated text throughout each 
noted section/appendix 
To align guidance in this 
protocol amendment with 
GSK standards for liver 
events in oncology trials 
Section 7.1.2 QTc Stopping 
Criteria 
Added new section on QTc 
stopping criteria 
To align with safety 
monitoring requirements for 
dostarlimab 
Section 8.1.2.1.1 Timing and 
Considerations for Radiologic 
Assessments 
Added text permitting 
collection of participant scan 
data 
To permit – per protocol – 
the collection of participant 
scan data under specific 
circumstances such as 
investigation of a significant 
safety event 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 192 of 213 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 8.1.2.2. Bone 
Marrow Assessments 
Added text describing timing 
of bone marrow assessment 
post-baseline if participant’s 
bone marrow was positive for 
disease at baseline. 
To align text in Section 
8.1.2.2 with that in Section 
1.3, Table 3 Schedule of 
Activities for bone marrow 
assessment 
Section 8.2.12 Laboratory 
Assessments 
• 
Replaced Baseline with 
Cycle 1 Day 1 
• 
Added guidance about 
timing of laboratory 
assessments at screening 
and Cycle 1 Day 1. 
• 
Added MDS/AML safety 
language  
• 
Formatted as table all 
measured lab parameters 
To adopt a more precise term 
than “Baseline” 
To clarify that Cycle 1 Day 1 
laboratory samples did not 
need to be collected if 
collected for Screening less 
than 7 days prior 
To describe laboratory 
assessments that must be 
conducted if MDS/AML is 
suspected 
Reformatted list of 
laboratory parameters for 
easier reading 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 193 of 213 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 8.4 
Pharmacokinetics, 
Immunogenicity and 
Biomarkers 
Section 8.4.1 PK Sample 
Collection 
Section 8.4.2 
Immunogenicity Sample 
Collection 
• 
PK, Immunogenicity, 
Exploratory sample 
collection Sections moved 
from Section 8.1.2 
Secondary Efficacy 
Endpoints to Section 8.4 
Pharmacokinetics, 
Immunogenicity, and 
Biomarkers 
To combine in one section 
all study procedures related 
to PK, immunogenicity, and 
biomarker sample collection 
and intent for analysis. 
Descriptive statements about 
statistical analyses of data 
from the results of these 
procedures were moved to 
Section 9 Statistical 
Considerations 
 
 
 
 
Section 8.4.2 
Immunogenicity Sample 
Collection  
Section 9.3.3.5. 
Immunogenicity Analysis 
Added content “The number 
and percentage of participants 
who become positive for 
ADAs and who develop 
neutralising antibodies will be 
summarized” 
To reflect the latest 
information regarding ADA 
Endpoint 
Section 9.3.3.2 Safety 
Analyses 
Added new content “(90 days 
for SAEs)”, “for both AEs and 
SAEs”, and replaced word 
“subsequent” with “new” 
To reflect the latest 
information regarding safety 
analyses 
CCI
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 194 of 213 
Section(s) Affected 
Description of Change 
Brief Rationale 
Appendix 1 – Committees 
Structure 
Updated information for 
establishment and 
composition of an 
independent data oversight 
committee 
To clarify that a committee 
that is independent of all 
aspects of the study and that 
is dedicated to oversight of 
safety and efficacy data from 
participants in Part 2 will be 
established. To clarify that 
details of committee 
composition and function 
will be described in a formal 
charter. 
Appendix 1 – Dissemination 
of Clinical Study Data 
Removed redundant text: 
GSK intends to make 
anonymised 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 participant 
care. This helps ensure the 
data provided by trial 
participants are used to 
maximum effect in the 
creation of knowledge and 
understanding 
To remove text that was 
redundant with text already 
present in this section. 
Appendix 2 Adverse Events 
and Serious Adverse Events: 
Definitions and Procedures 
for Recording, Evaluating, 
Follow-Up, and Reporting – 
Definition of an Adverse 
Event of Special Interest 
Deletion of AE “pneumonitis” 
and “embryo-fetal toxicity” 
from definition of Niraparib 
AESIs 
Updated to reflect the latest 
information regarding 
definition of Niraparib 
AESIs 
Appendix 5. Guidelines for 
Assessment of Disease, 
Disease Progression and 
Response Criteria in 
Participants with 
Neuroblastoma – Adapted 
From Revised International 
Neuroblastoma Response 
Criteria (INRC) 
Added new INRC Appendix 
Included to provide 
necessary and supportive 
guidance to sites carrying out 
disease assessments for 
participants with 
neuroblastoma. 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 195 of 213 
Amendment 04 (12 Dec 2024) 
Overall Rationale for Amendment 04: 
Amendment 04 is a substantial global amendment resulting in changes in participant 
dosing regimen(s) based on emerging data and safety information. Administrative, 
editorial, and clarifications for study conduct are also included.  
A general description and brief rationale(s) for key changes are provided in Table 2 
below. The synopsis was also updated to align with the changes in the protocol body, 
where applicable. 
Table 2 Summary of Changes for Amendment 04 
Section(s) Affected 
Description of Change 
Brief Rationale 
Headers, Title Page, 
abbreviations, Protocol 
Amendment Summary of 
Changes, List of 
Abbreviations, 
Appendices, References, 
and throughout 
Section 6 Study 
Treatments and 
Concomitant Therapy 
Section 6.2.5 Study 
Treatment Handling and 
Disposal 
Section 8.2.2 
Demographic/Medical 
History 
Section 8.3.2 Method of 
Detecting AEs and SAEs 
Section 8.3.4 Regulatory 
Reporting Requirements 
for SAEs 
Headers and title page updated with new document 
numbers, dates, and amendment information; 
Protocol Amendment Summary of Changes section 
was updated to include details and rationales for 
this amendment; editorial revisions for consistency 
with Sponsor’s ways of working, minor corrections 
and formatting adjustments, and to add clarification 
and/or remove discrepancies 
Editorial changes to align with the 
Sponsor’s standard protocol 
template, style guide, and ways of 
working and for accuracy, clarity, 
conformity, flow, and 
typographical error correction. 
Throughout 
 
 
 
Section 1.2 Schemas, 
Figure 1 
Section 2.6.3.1 Niraparib 
Dosing 
Section 2.6.3.2 
Dostarlimab dose 
Table 8 Objectives and 
Endpoints for Study 
213406 
Section 4 Overall Design 
Section 4.1.1 
• New Figure 1 outlining overall study schema and 
Part 1B study schema (new Figure 5); updated 
figure numbering throughout  
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 196 of 213 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 4.1.2 Part 1B 
Design 
Figure 5 Part 1B Study 
Schema Under Protocol 
Amendment 04 
Section 4.2 Intra-
participant Dose 
Escalation 
Section 4.4 General Study 
Conduct 
Section 4.5 Number of 
Participants 
Section 4.6 Treatment 
Assignment 
Section 4.7 Dose 
Adjustment Criteria. 
Section 5.1 Participant 
Inclusion Criteria 
Section 6.1 Study 
Treatments Administered 
Section 6.2.1 Study 
Treatment Packaging and 
Labelling 
Section 6.2.3.1 Niraparib 
Section 6.2.3.2 
Dostarlimab 
Section 6.4 Study 
Treatment Compliance 
Section 9 Statistical 
Considerations 
Section 9.1 Sample Size 
Determination 
Appendix 13 Part 1B 
Cohort A Niraparib Dose 
Reduction 
Recommendations for 
AEs 
• Part 2 primary objective text adjusted to include 
safety and tolerability to reflect updated 
objectives of Safety Run-in outlined in 
supplements A and B 
• Update overall design to reflect updated dosing, 
updated details for completed portions of the 
study, and mention of Safety Run-in for Part 2, 
where applicable  
• Minor changes to Part 1A study design to reflect 
study pause in enrolment and results from data 
collected  
• 
 
 
 
 
 
 
• Included details for treatment assignment for 
those participants that turn 18 years of age while 
on study expected to stay on TfOS niraparib 
formulation 
• New section added describing dose adjustments 
and criteria for adjustments due to changes in 
age and weight, along with subsections heading 
for AEs 
• Inclusion Criterion #2 updated to outline age 
enrolment requirements under Amendment 04 
• 
 
 
 
• Number of participants updated to include actual 
numbers of participants enrolled to date and 
planned enrolment numbers under 
Amendment 04 with updated study design 
cohort; includes minor update to planned 
cohorts for Part 1B under Protocol Amendment 
04 
• 
 
 
 
 
  
 
 
 
CCI
CCI
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 197 of 213 
Section(s) Affected 
Description of Change 
Brief Rationale 
• New dose reduction table for haematological 
AEs for Part 1B Cohort A based on the revised 
dosing regimen 
Section 4.7.2.1 Niraparib 
Table 9: Niraparib Dose 
modifications for 
Nonhematologic Adverse 
Reaction 
Table 10: Niraparib dose 
modification for 
haematologic adverse 
reaction 
• Updated to include details on number of 
permitted dose reductions 
• Updates to requirements for dose modification 
details for haematological and non-
haematological events  
Updated to align with safety 
management requirements for 
niraparib. 
Section 4.7.2 Dose 
Adjustment for Adverse 
Events 
Section 4.7.2.2 
Dostarlimab 
Table 11: Guidelines for 
Treatment of Immune-
Related Adverse Events 
• Updated details for dose adjustments for 
dostarlimab due to AEs including table outlining 
guidelines for treatment of imAEs 
Updated to align with safety 
management requirements for 
dostarlimab. 
Section 2.6.1.1 Niraparib 
Monotherapy 
• Table 5 Summary of Risks and Mitigations for 
Niraparib updated 
To align with current important 
identified and potential risks for 
niraparib as defined in the EU 
RMP 
Section 2.6.1.2 
Dostarlimab monotherapy 
• Table 6 Summary of Risks and Mitigations for 
Dostarlimab updated  
To align with current important 
identified and potentials risks for 
dostarlimab as defined in the EU 
RMP 
Section 3, Table 8 
Objectives and Endpoints 
for Study 213406 
Section 9.3.4 Exploratory 
Endpoints 
Section 5.1 Participant 
Inclusion Criteria 
• Inclusion Criterion #6: organ function 
parameters updated for haemoglobin  
To align with the patient 
population 
Section 1.3 Schedule of 
Assessments (Table 3 
footnote) 
Section 4.4 General Study 
Conduct 
Section 5.1 Inclusion 
Criteria (Criterion 7c) 
Section 8.2.9 Pregnancy 
Testing 
• Clarification included that WOCBP must have a 
pregnancy test even if they had received 
treatment that potentially but not definitely would 
prohibit becoming pregnant 
• Timeline for providing negative pregnancy test 
result updated to 24 hours 
Updated to increase assurance 
that female participant of 
childbearing potential is not 
pregnant as close as possible to 
time of study drug dosing. 
Section 5.2 Participant 
Exclusion Criteria 
• Exclusion Criterion #5 – Clarification participants 
with previously treated CNS metastases for 
evidence of disease progression 
Updated text to provide more 
accurate description of changes 
indicative of progression of 
disease in brain. 
Section 5.2. Participant 
Exclusion Criteria 
Appendix 12 
Consideration for 
• Exclusion Criterion 12 – updated wording 
regarding HbsAg/HbcAB for HBV screening 
• New Appendix 12 added for guidance 
surrounding HBV testing 
To permit the inclusion of patients 
with past HBV infection. 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 198 of 213 
Section(s) Affected 
Description of Change 
Brief Rationale 
Participants with Past 
HBV Infection 
Section 5.2. Participant 
Exclusion Criteria 
• New exclusion criteria 23 and 24 added 
regarding HCV testing  
To align with current protocol 
template language. 
Section 5.2. Participant 
Exclusion Criteria 
• Exclusion criterion #9 – updated language 
regarding when breastfeeding can resume 
To align with guidance in current 
US prescribing information for 
niraparib and dostarlimab. 
Section 5.2. Participant 
Exclusion Criteria 
• Exclusion criterion #15 – updated language 
regarding AEs in participants undergoing 
systemic anticancer therapy with exceptions as 
agreed with Sponsor. 
Expansion of text to more clearly 
define conditions for participant 
eligibility.  
Section 7.1.1 Liver 
Chemistry Stopping 
Criteria 
Appendix 8 Liver Safety: 
Required Actions, 
Monitoring, and Follow-Up 
to Assess Causality of 
Liver Event 
• Figure updated 
• Liver monitoring details updated in the Appendix 
Updated for patient safety in 
alignment with Sponsor template. 
Section 4.4 General Study 
Conduct 
Section 7.1 
Discontinuation of Study 
Treatment 
Section 7.2 Withdrawal of 
Consent 
Section 7.3 Participant 
Discontinuation/ 
Withdrawal from the 
Clinical Study 
• Text adjusted to clarify discontinuation reasons 
and requirements should alternative anticancer 
therapy be started, including expectations for 
Safety FU period 
• Text added acknowledging if in-person visits are 
not possible 
• Text added regarding data collection from public 
domains following withdrawal of consent 
• Additional updates to align wording and align 
with Sponsor template and EU CTR 
requirements 
Clarification for study conduct and 
to align with Sponsor template 
and the program. 
Section 1.3 Schedule of 
Assessments (including 
footnote) 
Section 4.7.1 Dose 
Adjustment for Age and 
Weight 
• CBC with differentials assessments updated to 
include twice weekly collection in Cycles 1 and 
2, and after a niraparib dose increased due to a 
birthday or weight change; including footnote 
updates 
To permit more frequent 
monitoring of haematology values 
(particularly for platelets) to permit 
early rapid detection of onset of 
thrombocytopenia over the first 2 
cycles of treatment and additional 
safety monitoring in response to 
an increase in niraparib dose and 
to allow use of testing at facilities 
outside the research clinic. 
Section 4.8 End of Study 
Definition 
Section 6.7 Continued 
Access to Study 
Intervention After the End 
of the Study 
• Updated wording in end of study definition 
Clarification for study conduct 
Section 5.1. Participant 
Inclusion Criteria 
• Criterion #1: replaced statement ‘local curative 
treatment.’ with ‘alternative curative 
treatment.’ 
Clarification 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 199 of 213 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 1.3. Schedule of 
Activities (including 
footnote) 
Section 4.4 General Study 
Conduct 
Section 8.4 
Pharmacokinetics, 
Immunogenicity, and 
Biomarkers 
Clarification for study conduct and 
alignment with Sponsor 
requirements for sample storage 
Section 1.3. Schedule of 
Activities (including 
footnote) 
Section 8.2.7. Vital Signs, 
Height, and Weight 
• Updated timing for collection of vital signs, 
height, and weight measurements including 
during follow-up period and clarifications for 
measuring height and weight. 
Clarification for study conduct to 
permit consistent monitoring of 
vital signs throughout the 
Treatment Period. 
Section 2.1.1 Clinical Data 
for Niraparib 
Section 2.2.1 Clinical Data 
for Dostarlimab 
Section 2.3 Rationale for 
Synergy Between PARP 
Inhibitors and Immune 
Checkpoint Inhibitors 
Section 2.6.1.3 Niraparib 
and Dostarlimab 
Combination Safety and 
Efficacy 
• Update regulatory, clinical, and safety 
information and added references to IBs 
Editorial updates to align with 
current information for the 
investigation products. 
Section 1.3 Schedule of 
Activities (Table 3, 
footnote) 
Table 4 Tumour 
Assessment Flowchart 
Section 4.4 General Study 
Conduct 
Section 8.1.2.1 
Radiological Assessment 
• Clarification that brain scans must include IV 
contrast and brain scan by MRI preferred to that 
by CT including in table footnote and Table 4 
outlining tumour assessments 
• Clarifications in imaging requirements for 
participants at time of study treatment 
discontinuation  
• Added statement regarding follow-up disease 
assessments for participants with CR or PR 
while on treatment, who discontinue  
• Addition of Schwartz, 2016 reference for 
RECIST 
Clarification for study conduct. 
Section 1.3 Schedule or 
Assessments (footnote) 
Section 8.2 Assessment 
of Safety 
Section 8.4 
Pharmacokinetics, 
Immunogenicity, and 
Biomarkers 
• Detail included regarding prioritisation of blood 
sample collection in the event of concerns for 
excessive blood volume withdrawal 
Clarification for study conduct to 
provide guidance to sites on 
relative importance of collection of 
specific blood samples.  
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 200 of 213 
Section(s) Affected 
Description of Change 
Brief Rationale 
 
 
Section 1.3 Schedule of 
Assessments (including 
footnotes) 
Table 4: Tumour 
Assessment Flowchart 
Section 4.4 General Study 
Conduct 
Section 8.1.2.1 
Radiological Assessments 
Appendix 4 Guidelines for 
Assessment of Disease, 
Disease Progression, and 
response Criteria – 
Adapted from RECIST 
Appendix 5 Guidelines for 
Assessment of Disease, 
Disease Progression and 
Response Criteria in 
Participants with 
Neuroblastoma – Adapted 
from Revised International 
Neuroblastoma Response 
Criteria (INRC) 
• Adjusted wording in Table 3 and Table 4 
surrounding tumour assessments for clarification 
and align discontinuation wording 
• Guidelines for Assessments using RECIST 
updated to align with guidelines to include 
definitions of non-target and target lesions for 
evaluation and removal of best overall response 
information  
• Schwartz, 2016 reference included for RECIST 
• Minor updates in INRC guidelines Table 23 
regarding tumour response at metastatic soft 
tissue and bone sites PD definition 
Updates to ensure key imaging 
assessments conducted 
appropriately and consistently. 
Clarifications of standard disease 
assessment criteria. Best overall 
response details removed as this 
is determined programmatically by 
Sponsor.  
Section 1.3 Schedule of 
Assessments (including 
footnote) 
Section 8.4.3 Exploratory 
biomarkers 
• 
 
  
Clarification. 
Section 4.4 General Study 
Conduct 
Section 8.3.1 Time Period 
and Frequency of 
Collecting AE/SAE 
Information 
Section 8.3.3 Follow-up of 
SAEs 
• Adjusted wording surrounding collection and 
follow-up of nonserious AEs, and expectations 
for follow-up of SAEs during long-term follow-up 
period and when starting alternative anticancer 
therapy. 
Clarification for study conduct. 
Section 6.7 Continued 
Access to Study 
Treatment 
• Section added per protocol template to clarify 
intended access to treatment for participants in 
the study following completion. 
Clarification for study conduct and 
alignment with Sponsor template. 
Section 7.1.2 QTc 
Stopping Criteria 
• Adjusted wording regarding ECG reading 
requirements 
To align text with standard 
program language. 
Section 8.2.12 Laboratory 
assessments 
Table 15: Safety 
Laboratory Assessments 
• Note included regarding baseline platelet count 
of 100 000/uL in this study 
• Added reference to table of tests to be 
performed, AESI term updated, text added to 
clarify handling of clinically significant values 
and AE reporting per Sponsor template 
• Footnote added to Table 15 regarding values to 
be recorded (either absolute counts or 
percentages) for differential values 
Clarifications included rationale 
for baseline platelet count, for 
study conduct, and to align with 
Sponsor template. 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 201 of 213 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 8.2.1 Safety 
Parameters 
Appendix 2 Adverse 
Events and Serious 
Adverse Events: 
Definitions and 
Procedures for Recording, 
Evaluating, Follow-up, 
and Reporting 
• Urinalysis wording updated to clarify urinalysis is 
not being conducted regularly, but only under 
certain circumstances 
Clarification for study conduct 
Section 8.2.3 Disease 
History 
• Removed ‘for participants with neuroblastoma 
only’ from stage of initial diagnosis collection 
• Deleted collection of ‘previously treated but 
currently stable CNS metastases’ 
Clarification for study conduct to 
not limit data collection for initial 
diagnosis data collection and 
aligned collection regarding CNS 
disease with data collection per 
CRFs. 
Section 8.3.5. Pregnancy 
• Deleted statements related to female participant 
becoming pregnant during the study and 
continuation of treatment. Additional 
clarifications added regarding sharing pregnancy 
information. 
For consistency with Section 7.1 
and Sponsor template. 
Section 8.3.6 AESI 
• Updated term relating to second primary 
malignancies and added statement that there 
are no AESIs for dostarlimab 
• Clarifying language added surrounding AESI 
collection timing. 
Clarification to align with current 
safety information and text within 
protocol. 
Section 8.5 Genetics 
• 
 
 
Clarification. 
Appendix 1 Regulatory, 
Ethical, and Study 
Consideration 
• Added additional information under recruitment 
strategy, data protection, dissemination of 
clinical study data, data quality assurance, 
source documents and study/site termination, 
and publication policy 
To align with EU CTR 
requirements and Sponsor 
template. 
Appendix 2: Adverse 
Events and Serious 
Adverse Events: 
Definitions and 
Procedures for Recording, 
Evaluating, Follow-up, 
and Reporting 
• Included TEAE definition, severity grades for 
intensity, updated information on assessment of 
causality with more than 1 intervention, outcome 
assessment options added, and detail included 
regarding AE/SAE/pregnancy follow-up 
Clarification for study 
conduct/reporting and to align with 
Sponsor template. 
Appendix 3 contraception 
guidelines 
• Updated definitions for WOCBP 
To align with updated Sponsor 
definition. 
Abbreviations: 
; ADA=antidrug antibody(ies); AE=adverse event; AESI=AE 
of special interest; CBC=complete blood count; CNS=central nervous system; CR=complete response; CRF=case 
report form; CT=computed tomography; CTCAE=common terminology criteria for Adverse Events; CTR=Clinical 
Trials Regulations; EU=European Union; ; FU=follow-up; HbcAB=hepatitis B core antibody, HBsAg = hepatitis B 
surface antigen; HBV = hepatitis B virus; HCV=hepatitis C virus; IB=investigator’s brochure; INRC=International 
Neuroblastoma Response Criteria; imAE=immune-mediated AE; MRI=magnetic resonance imaging; PD=progressive 
disease; PR=partial response; RECIST=Response Evaluation Criteria in Solid Tumours; RMP=risk management 
plan; SAE=serious AE; SoA=schedule of assessments; TEAE=treatment-emergent AE: TfOS=tablet for oral 
suspension; WOCBP=woman of childbearing potential. 
 
Amendment 04 GBR-1 (08 Aug 2024) 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 202 of 213 
Overall Rationale for Amendment 04 GBR-1: 
Amendment 04 GBR-1 is a UK-specific amendment addressing agency feedback 
regarding exclusion criterion 15. A description and rationale for the changes is provided 
in Table 2 below.  
Table 2: Summary of Changes for Amendment 04 GBR-1 
Section(s) Affected 
Description of Change (deleted text; added text) 
Brief Rationale 
Headers, Title Page, 
Protocol Amendment 
Summary of Changes, 
Appendix 11 Country-
specific Requirements 
Headers and title page updated with new document 
amendment number/approval date, and amendment 
information; Protocol Amendment Summary of Changes 
section was updated to include details and rationale for 
this amendment; country-specific appendix for global 
amendments removed (remaining appendices 
renumbered) and associated text in protocol 
sections/tables adjusted. 
Editorial changes to align 
with the Sponsor’s 
standard protocol template, 
style guide, and ways of 
working. 
Synopsis 
Section 5.2 Participant 
Exclusion Criteria 
Exclusion criterion #15 updated as follows: 
Participant has not recovered (i.e., to Grade ≤1 or to 
baseline) from systemic anticancer therapy-induced AEs. 
Note: Participants with certain AEs that are considered 
either nonclinically significant or are deemed stable or 
irreversible are exceptions to this criterion and may qualify 
for the study after discussion with the GSK Medical 
Monitor. Examples of AEs include, but are not limited to, 
alopecia, hearing impairment, alopecia, Grade ≤2 
neuropathy, Grade ≤2 fatigue, Grade ≤2 anaemia, and/or 
Grade ≤2 neutropenia are an exception to this criterion 
and may qualify for the study. 
Regulatory agency 
feedback. 
 
 
 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 203 of 213 
12. 
REFERENCES 
Ady N, Zucker JM, Asselain B, Edeline V, Bonnin F, Michon J et al. A new 123I-MIBG 
whole body scan scoring method: Application to the prediction of the response of 
metastases to induction chemotherapy in stage IV neuroblastoma. Eur J Cancer. 
1995;31A(2):256-61. 
 
Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SJR, Behjati S, Biankin AV, et al. 
Signatures of mutational processes in human cancer. Nature. 2013;500:415-421. 
 
Andrade RJ, Robles M and Lucena MI. Rechallenge in drug-induced liver injury: the 
attractive hazard. Expert Opin Drug Saf. 2009;8(6):709-714. 
 
Barber GN. STING: infection, inflammation and cancer. Nat Rev Immunol. 
2015;15(12):760-770. 
 
Boberg M, Vrana M, Mehrotra A, et al. Age-dependent absolute abundance of hepatic 
carboxylesterases (CES1 and CES2) by LC-MS/MS proteomics: Application to PBPK 
modeling of oseltamivir in vivo pharmacokinetics in infants. Drug Metab. Dispos. 
2017;45(2):216-223 
 
Bowers PM, Horlick RA, Neben TY, Toobian RM, Tomlinson GL, Dalton JL, et al. 
Coupling mammalian cell surface display with somatic hypermutation for the discovery 
and maturation of human antibodies. Proc Natl Acad Sci U S A. 2011;108(51):20455-
20460. 
 
Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM, et al. 
Management of Immune-Related Adverse Events in Patients Treated With Immune 
Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice 
Guideline. J Clin Oncol. 2018: JCO2017776385. 
 
Brahmer JR, Abu-Sbeih H, Ascierto PA, et al. Society for Immunotherapy of Cancer 
(SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events. 
J Immunother Cancer. 2021;9(6):e002435. doi: 10.1136/jitc-2021-002435. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 204 of 213 
 
Brahmer JR, Lacchetti C, Schneider BJ, Management of Immune-Related Adverse 
Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American 
Society of Clinical Oncology Clinical Practice Guideline (ASCO). Journal of Clinical 
Oncology. 2021. 
 
Burchill SA, Beiske K, Shimada H, Ambros PF, Seeger R, Tytgat GAM et al: 
Recommendations for the standardization of bone marrow disease assessment and 
reporting in children with neuroblastoma on behalf of the International Neuroblastoma 
Response Criteria Bone Marrow Working Group. Cancer 2017;123:1095-105. 
 
Chen EX, Jonker DJ, Siu LL, McKeever K, Keller D, Wells J, et al. A Phase I study of 
olaparib and irinotecan in patients with colorectal cancer: Canadian Cancer Trials Group 
IND 187. Invest New Drugs. 2016;34(4):450-457. 
 
Chen L and Han X. Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future. 
J Clin Invest. 2015;125(9):3384-3391. 
 
Chornenkyy Y, Agnihotri S, Yu M, Buczkowicz P, Rakopoulos P, Golbourn B, et al. 
Poly-ADP-ribose polymerase as a therapeutic target in pediatric diffuse intrinsic pontine 
glioma and pediatric high-grade astrocytoma. Mol Cancer Ther. 2015;14(11):2560-2568. 
 
Choy E, Butrynski JE, Harmon DC, Morgan JA, George S, Wagner AJ, et al. Phase II 
study of olaparib in patients with refractory Ewing sarcoma following failure of standard 
chemotherapy. BMC Cancer. 2014;14:813. 
 
Chugh R and Reinke D (2017). A phase I study of the poly-ADP ribose polymerase 
(PARP) inhibitor, niraparib (NIR), in combination with temozolomide (TMZ) in patients 
with advanced ewing sarcoma (ES): final results of SARC025 arm 1. Poster presented at 
the CTOS Annual Meeting. 
 
Clopper C and Pearson ES. The use of confidence or fiducial limits illustrated in the case 
of the binomial. Biometrika. 1934;26:404-413. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 205 of 213 
 
D'Addio F, Riella LV, Mfarrej BG, Chabtini L, Adams LT, Yeung M, et al. The link 
between the PDL1 costimulatory pathway and Th17 in fetomaternal tolerance. J 
Immunol. 2011;187(9):4530-4541. 
 
Dean E, Middleton MR, Pwint T, Swaisland H, Carmichael J, Goodege-Kunwar P, et al. 
Phase I study to assess the safety and tolerability of olaparib in combination with 
bevacizumab in patients with advanced solid tumours. Br J Cancer. 2012;106(3):468-474. 
 
Ding L, Kim HJ, Wang Q, Kearns M, Jiang T, Ohlson CE, et al. PARP Inhibition Elicits 
STING-Dependent Antitumour Immunity in Brca1-Deficient Ovarian Cancer. Cell Rep. 
2018;25(11):2972-2980.e2975. 
 
Dong H, Zhu G, Tamada K and Chen L. B7-H1, a third member of the B7 family, co-
stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 1999;5(12):1365-
1369. 
 
Dostarlimab Investigator's Brochure. (GSK document No. RPS-CLIN-029721), or most 
recent version 
 
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New 
response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). 
Eur J Cancer. 2009;45(2):228-247. 
 
Engert F, Kovac M, Baumhoer D, Nathrath M and Fulda S. Osteosarcoma cells with 
genetic signatures of BRCAness are susceptible to the PARP inhibitor talazoparib alone 
or in combination with chemotherapeutics. Oncotarget. 2017;8(30):48794-48806. 
 
Engert F, Schneider C, Weibeta LM, Probst M and Fulda S. PARP inhibitors sensitize 
Ewing sarcoma cells to temozolomide-induced apoptosis via the mitochondrial pathway. 
Mol Cancer Ther. 2015;14(12):2818-2830. 
 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 206 of 213 
Federico SM, Stewart E, Coleman JL, Bishop MW, Santana VM, Lam C, et al. Phase I 
study of talazoparib and irinotecan in children and young adults with recurrent/refractory 
solid tumours. Journal of Clin Oncol. 2017;35(15_suppl):10542-10542. 
 
Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, et al. Engagement 
of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative 
regulation of lymphocyte activation. J Exp Med. 2000;192(7):1027-1034. 
 
Garnett MJ, Edelman EJ, Heidorn SJ, Greenman CD, Dastur A, Lau KW, et al. 
Systematic identification of genomic markers of drug sensitivity in cancer cells. Nature. 
2012;483(7391):570-575. 
 
Geoerger B, Kang HJ, Yalon-Oren M, Marshall LV, Vezina C, Pappo AS, et al. Phase 
1/2 KEYNOTE-051 study of pembrolizumab (pembro) in pediatric patients (pts) with 
advanced melanoma or a PD-L1+ advanced, relapsed, or refractory solid tumour or 
lymphoma. J Clin Oncol. 2017;35(Suppl; abstr 10525). 
 
Gonzalez-Martin A, Pothuri B, Vergote I, DePont Christensen R, Graybill W, Mirza MR, 
et al. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J 
Med. 2019;381(25):2391-2402. 
 
Gröbner SN, Worst BC, Weischenfeldt J, Buchhalter I, Kleinheinz K and Rudneva VA. 
The landscape of genomic alterations across childhood cancers. Nature. 
2018;555(7696):321-327. 
 
GSK3985771 IB GlaxoSmithKline, Report Date 21-Jun-2022. 
 
GSK4057190A IB GlaxoSmithKline, Report Date 20-Apr-2022.  
 
Guo W, Wang SJ, Yang S, Lynn H and Ji Y. A Bayesian interval dose-finding design 
addressingOckham's razor: mTPI-2. Contemp Clin Trials. 2017;58:23-33. 
 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 207 of 213 
Halford SER, Cruickshank G, Dunn L, Erridge S, Godfrey L, Herbert C, et al. Results of 
the OPARATIC trial: A phase I dose escalation study of olaparib in combination with 
temozolomide (TMZ) in patients with relapsed glioblastoma (GBM). J Clin Oncol. 
2017;35(15_suppl):2022-2022. 
 
Haanen J, Carbonnel F, Robert C, Kerr KM, Peters S, Larkin J, et al. Management of 
toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, 
treatment and follow-up. Ann Oncol. 2017;28(suppl_4):iv119-iv142. 
 
Haanen J, Obeid M, Spain L, et al. Management of toxicities from immunotherapy: 
ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up Annals Of 
Oncology, 2022 33(12):1217-1238 
 
Hartlova A, Erttmann SF, Raffi FA, Schmalz AM, Resch U, Anugula S, et al. DNA 
damage primes the type I interferon system via the cytosolic DNA sensor STING to 
promote anti-microbial innate immunity. Immunity. 2015;42(2):332-343. 
 
Harttrampf AC, Lacroix L, Deloger M, Deschamps F, Puget S, Auger N, et al. Molecular 
screening for cancer treatment optimization (MOSCATO-01) in pediatric patients: a 
single-institutional prospective molecular stratification trial. Clin Cancer Res. 
2017;23(20):6101-6112. 
 
Hopp Children’s Center Heidelberg. A molecular map of childhood tumors. PedPanCan. 
PedPanCan Datacommons. Accessed from: https://www.kitz-
heidelberg.de/en/research/datacommons/pedpancan/ 
 
Huang J, Wang L, Cong Z, Amoozgar Z, Kiner E, Xing D, et al. The PARP1 inhibitor 
BMN 673 exhibits immunoregulatory effects in a Brca1(-/-) murine model of ovarian 
cancer. Biochem Biophys Res Commun. 2015;463(4):551-556. 
 
Hunt CM. Mitochondrial and immunoallergic injury increase risk of positive drug 
rechallenge after drug-induced liver injury: a systematic review. Hepatology. 
2010;52(6):2216-2222. 
 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 208 of 213 
IARC (2017). International Incidence of Childhood Cancer, Volume III. Steliarova-
Foucher E, Colombet M, Ries LAG et al. Lyon, France, International Agency for 
Research on Cancer. 
 
Ishida Y, Agata Y, Shibahara K and Honjo T. Induced expression of PD-1, a novel 
member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO 
J. 1992;11(11):3887-3895. 
 
James LP, Letzig L, Simpson PM, Capparelli E, Roberts DW, Hinson JA, et al. 
Pharmacokinetics of acetaminophen-protein adducts in adults with acetaminophen 
overdose and acute liver failure. Drug Metab Dispos. 2009;37(8):1779-1784. 
 
Ji Y and Wang SJ. Modified toxicity probability interval design: a safer and more reliable 
method than the 3 + 3 design for practical phase I trials. J Clin Oncol. 2013;31(14):1785-
1791. 
 
Jiao S, Xia W, Yamaguchi H, Wei Y, Chen MK, Hsu JM, et al. PARP Inhibitor 
Upregulates PD-L1 Expression and Enhances Cancer-Associated Immunosuppression. 
Clin Cancer Res. 2017;23(14):3711-3720. 
 
Kabir TF, Chauhan A, Anthony L and Hildebrandt GC. Immune Checkpoint Inhibitors in 
Pediatric Solid Tumours: Status in 2018. Ochsner J. 2018;18(4):370-376. 
 
Kara L. Davis, Elizabeth Fox, Joel M. Reid, Xiaowei Liu, Charles G. Minard, Brenda 
Weigel, et al. Initial results of a phase I/II study of nivolumab and ipilimumab in 
pediatric patients with relapsed/refractory solid tumours—A COG study. J Clin Oncol. 
2017;35(suppl; abstr 10526). 
 
Keir ME, Butte MJ, Freeman GJ and Sharpe AH. PD-1 and its ligands in tolerance and 
immunity. Annu Rev Immunol. 2008;26:677-704. 
 
Konstantinopoulos PA, Sachdev JC, Schwartzberg L, Matulonis UA, Sun P, Wang JY, et 
al. Dose-finding combination study of niarapib and pembrolizumab in patients (pts) with 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 209 of 213 
metastatic triple-negative breast cancer (TNBC) or recurrent platinum-resistant epithelial 
ovarian cancer (OC). Ann Oncol. 2017;28(5):403-427. 
 
Kovac M, Blattmann C, Ribi S, Smida J, Mueller NS, Engert F, et al. Exome sequencing 
of osteosarcoma reveals mutation signatures reminiscent of BRCA deficiency. Nat 
Commun. 2015;6:8940. 
 
Kurzrock R, Galanis E, Johnson DR, Kansra V, Wilcoxen K, McClure T, et al. A phase I 
study of niraparib in combination with temozolomide (TMZ) in patients with advanced 
cancer. J Clin Oncol. 2014;32(15_suppl):2092-2092. 
 
Laken H, Kehry M, McNeeley P, Neben T, Zhang J, Jenkins D, et al. Identification and 
characterization of TSR-042, a novel anti-human PD-1 therapeutic antibody. European 
Journal of Cancer. 2016;69 (Suppl. 1):S102. 
 
Latchman Y, Wood CR, Chernova T, Chaudhary D, Borde M, Chernova I, et al. PD-L2 is 
a second ligand for PD-1 and inhibits T cell activation. Nat Immunol. 2001;2(3):261-268. 
 
Le Gal F, Gordien E, Affolabi D, Hanslik T, Alloui C, Deny P, et al. Quantification of 
hepatitis delta virus RNA in serum by consensus real-time PCR indicates different 
patterns of virological response to interferon therapy in chronically infected patients. J 
Clin Microbiol. 2005;43(5):2363-2369. 
 
Lee JM, Cimino-Mathews A, Peer CJ, Zimmer A, Lipkowitz S, Annunziata CM, et al. 
Safety and Clinical Activity of the Programmed Death-Ligand 1 Inhibitor Durvalumab in 
Combination With Poly (ADP-Ribose) Polymerase Inhibitor Olaparib or Vascular 
Endothelial Growth Factor Receptor 1-3 Inhibitor Cediranib in Women's Cancers: A 
Dose-Escalation, Phase I Study. J Clin Oncol. 2017;35(19):2193-2202. 
 
Li T and Chen ZJ. The cGAS-cGAMP-STING pathway connects DNA damage to 
inflammation, senescence, and cancer. J Exp Med. 2018;215(5):1287-1299. 
 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 210 of 213 
Liu JF, Tolaney SM, Birrer M, Fleming GF, Buss MK, Dahlberg SE, et al. A Phase 1 trial 
of the poly(ADP-ribose) polymerase inhibitor olaparib (AZD2281) in combination with 
the anti-angiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triple-negative 
breast cancer. Eur J Cancer. 2013;49(14):2972-2978. 
 
Matthay KK, Edeline V, Lumbroso J, Tanguy ML, Asselain B, Zucker JM et al. 
Correlation of early metastatic response by 123I-metaiodobenzylguanidine scintigraphy 
with overall response and event-free survival in stage IV neuroblastoma. J Clin Oncol 
2003;21:2486-2491. 
 
Meade M (2016). Efficacy evaluation of niraparib and TSR-042 alone and in 
combination against subcutaneous BRKras-luc murine ovarian carcinoma in female FVB 
mice, Molecular Imaging. 
 
Mills G (2017). Efficacy of niraparib as a single agent and in combination with PD-1 
antibody in LPA1-T22 tumour model, TESARO, Inc. 
 
Mirza MR, Wang J, Mau-Sørensen M, Birrer MJ, Wang X, Jørgensen M, et al. 953PA 
phase 1 study to evaluate the safety and tolerability of bevacizumab-niraparib 
combination therapy and determine the recommended phase 2 dose (RP2D) in women 
with platinum-sensitive epithelial ovarian cancer (ENGOT-OV24/AVANOVA1). Annals 
of Oncology. 2017;28(suppl_5):mdx372.024-mdx372.024. 
 
Moore KN, Alvarez Secord A, Geller MA, Miller DS, Cloven N, Fleming GF, et al. 
Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a 
multicentre, open-label, single-arm, phase 2 trial. The Lancet Oncol. 2019;epub; 
https://doi.org/10.1016/S1470-2045(19)30029-4. 
 
National Comprehensive Cancer Network (NCCN) clinical practice guidelines in 
oncology (NCCN Guidelines) for management of immunotherapy-related toxicities 
(Version 1.2022). 28 February 2022. Accessed 07 October 2022 from: 
https://www.nccn.org/professionals/physician_gls/pdf/immunotherapy.pdf. 
 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 211 of 213 
Naidoo J, Murphy C, Atkins MB, et al. Society for Immunotherapy of Cancer (SITC) 
consensus definitions for immune checkpoint inhibitor-associated immune-related 
adverse events (irAEs) terminology. J Immunother Cancer 2023;11:e006398 
 
National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in 
Oncology (NCCN Guidelines), in Version 2.2021 
 
Niraparib Investigator's Brochure (GSK document No. RPS-CLIN-053021), or most 
recent version. 
 
Nishino M, Tirumani SH, Ramaiya NH and Hodi FS. Cancer immunotherapy and 
immune-related response assessment: The role of radiologists in the new arena of cancer 
treatment. Eur J Radiol. 2015;84(7):1259-1268. 
 
Papay JI, Clines D, Rafi R, Yuen N, Britt SD, Walsh JS, et al. Drug-induced liver injury 
following positive drug rechallenge. Regul Toxicol Pharmacol. 2009;54(1):84-90. 
 
Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev 
Cancer 2012; 4:252-64 
 
Park JR, Bagatell R, Cohn SL, Pearson AD, Villablanca JG, Berthold F, et al. Revisions 
to the International Neuroblastoma Response Criteria: A Consensus Statement From the 
National Cancer Institute Clinical Trials Planning Meeting. J Clin Oncol. 
2017;35(22):2580-2587. 
 
Parkes EE, Walker SM, Taggart LE, McCabe N, Knight LA, Wilkinson R, et al. 
Activation of STING-dependent innate immune signaling by S-phase-specific DNA 
damage in breast cancer. J Natl Cancer Inst. 2017;109(1). 
 
Patnaik A, Weiss GJ, Rasco DW, et al. Safety, antitumor activity, and pharmacokinetics 
of dostarlimab, an anti-PD-1, in patients with advanced solid tumors: a dose-escalation 
phase 1 trial. Cancer Chemother Pharmacol. 2022;89(1):93-103. doi: 10.1007/s00280-
021-04358-3. Epub 2021 Nov 8. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 212 of 213 
 
Ramalingam SS, Thara E, Awad MM, et al. JASPER: Phase 2 trial of first-line niraparib 
plus pembrolizumab in patients with advanced non-small cell lung cancer. Cancer. 
2022;128(1):65-74. doi: 10.1002/cncr.33885. Epub 2021 Sep 3 
 
Ramos-Casals M, Brahmer JR, Callahan MK, et al. Immune-related adverse events of 
checkpoint inhibitors. Nat Rev Dis Primers. 2020, 6(1):38 
 
Sachdev E, Tabatabai R, Roy V, Rimel BJ and Mita MM. PARP Inhibition in Cancer: An 
Update on Clinical Development. Target Oncol. 2019;14(6):657-679. 
 
Schwartz LH, Litière S, de Vries E, et al. RECIST 1.1-Update and clarification: From the 
RECIST committee. Eur J Cancer. 2016:132-7. 
 
Smith SJ, Long A, Barrow JH, Macarthur DC, Coyle B, Grundy RG, et al. Pediatric high-
grade glioma: identification of poly(ADP-ribose) polymerase as a potential therapeutic 
target. Neuro Oncol. 2011;13(11):1171-1177. 
 
 Smith TJ, Bohlke K, Lyman GH et al. Recommendations for the use of WBC growth 
factors: American Society of Clinical Oncology Clinical Practice Guideline Update. J 
Clin Oncol. 2015;33(28):3199-3212. 
 
Schwartz GJ, Muñoz A, Schneider MF, et al. New equations to estimate GFR in children 
with CKD. J Am Soc Nephrol. 2009;20(3):629-37.  
 
Tseng SY, Otsuji M, Gorski K, Huang X, Slansky JE, Pai SI, et al. B7-DC, a new 
dendritic cell molecule with potent costimulatory properties for T cells. J Exp Med. 
2001;193(7):839-846. 
 
US Department of Health and Human Services. National Institutes of Health. National 
Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE). Version 
5.0. 27 November 2017. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406_Master 
Protocol Amendment 05 
Page 213 of 213 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Q
uick_Reference_8.5x11.pdf 
 
Vinayak S, Tolaney SM, Schwartzberg L, Mita M, McCann G, Tan AR, et al. Open-
Label Clinical Trial of Niraparib Combined With Pembrolizumab for Treatment of 
Advanced or Metastatic Triple-Negative Breast Cancer. JAMA Oncol. 2019. 
 
Waligora M, Bala MM, Koperny M, Wasylewski MT, Strzebonska K, Jaeschke RR, et al. 
Risk and surrogate benefit for pediatric Phase I trials in oncology: A systematic review 
with meta-analysis. PLoS Med. 2018;15(2):e1002505. 
 
Weber JS, Practical management of immune-related adverse events from immune 
checkpoint protein antibodies for the oncologist. Am Soc Clin Oncol Educ 
Book 2012:174-7 
 
Xing D and Orsulic S. A mouse model for the molecular characterization of BRCA1-
associated ovarian carcinoma. Cancer Res. 2006;66(18):8949-8953. 
 
Zou W and Chen L. Inhibitory B7-family molecules in the tumour microenvironment. 
Nat Rev Immunol. 2008;8(6):467-477. 
 

Signature Page for  213406 TMF-20143904 v1.0
Signature Page for TMF-20143904 v1.0
Reason for signing: Approved
Name:
Role: Approver
Date of signature: 12-Dec-2024 21:31:08 GMT+0000
PPD

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 1 of 74 
TITLE PAGE 
SUPPLEMENT A 
PROTOCOL 213406 
PART 2: OSTEOSARCOMA EXPANSION COHORT 
Protocol Title: 
A PHASE 1, MULTICENTRE, OPEN-LABEL, DOSE 
ESCALATION AND COHORT EXPANSION STUDY OF 
NIRAPARIB AND DOSTARLIMAB IN PAEDIATRIC 
PATIENTS WITH RECURRENT OR REFRACTORY 
SOLID TUMOURS 
Protocol Number: 
213406 Amendment 05 
Compound Number or Name:  Niraparib (GSK3985771), Dostarlimab (GSK4057190A) 
Brief Title: 
Dose Escalation and Cohort Expansion Study of Niraparib 
and Dostarlimab in Paediatric Participants with Solid 
Tumours 
Study Phase: 
Phase 1 
Sponsor Name and Legal 
Registered Address: 
 
 
 
 
Medical Monitor Name and 
Contact Information: 
GlaxoSmithKline Research & Development Limited  
79 New Oxford Street 
London 
WC1A 1DG 
United Kingdom  
 
Contact Information can be found in the local study contact 
information 
Sponsor Signatory: 
 
 
Nidale Tarek, MD 
Senior Medical Director 
GSK 
Regulatory Agency 
Identifying Number(s): 
EudraCT Number: 2020‐002359‐39 
EU CT: 2024-511071-16 
Approval Date:  
17 Dec 2024 
Copyright 2024 the GSK group of companies. All rights reserved. Unauthorised copying or use 
of this information is prohibited. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 2 of 74 
PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Table 1: 
Document History 
Document 
Date 
Amendment 05 
17 Dec 2024 
Amendment 04 GBR-1 
08 Aug 2024 
Amendment 04 
23 May 2024 
Amendment 03 
20 July 2022 
Amendment 02 
23 November 2020 
Amendment 01 
16 October 2020 
Original Protocol 
12 May 2020 
Amendment 05 (17 Dec 2024) 
Overall rationale for the current Amendment:  
Protocol Amendment 05 is a substantial amendment that aligns Protocol Amendment 04 with all 
aspects of the UK-specific Protocol Amendment 04 GBR-1, resulting in a single global 
amendment. Additional changes include an update of the sponsor’s legal registered address plus 
administrative and editorial updates and clarifications for study conduct. 
A general description and brief rationale(s) for key changes are provided in Table 2 below. The 
synopsis was also updated to align with the changes in the protocol body, where applicable. 
Table 2 
List of main changes in the protocol and their rationale: 
Section # and title 
Description of change 
Brief rationale 
Title Page 
Sponsor legal address update 
To align with current GSK policy 
Section 1.1 Synopsis Methodology] 
Section 4.1 Overall Study Design 
Language updated to indicate that 
the dose escalation committee (DEC) 
will review safety data and will 
determine future enrollment plan 
To more clearly describe the role of the 
DEC in safety data review process 
overall  
Section 1.1 Synopsis 
Main Criteria for Inclusion; Section 5.1 
Participant Inclusion Criteria Point 03 
Addition of relevant time point (“at 
screening”) 
To clearly indicate at what point in the 
study disease characteristics were to be 
evaluated  
Section 1.1 Synopsis 
Main Criteria for Exclusion; Section 5.2 
Participant Exclusion Criteria Point 17 
Participant has not recovered (i.e., to 
Grade ≤1 or to baseline) from prior 
systemic anticancer therapy-induced 
AEs. Note: Participants with alopecia, 
hearing impairment, Grade ≤2 
neuropathy, Grade ≤2 fatigue, Grade 
≤2 anaemia, and/or Grade ≤2 
neutropenia are an exception to this 
criterion and may qualify for 
participation in the study. 
To revert the wording to that in Protocol 
Amendment 04, which provided more 
specific criteria for enrollment of 
participants with ongoing toxicities.   

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 3 of 74 
Section # and title 
Description of change 
Brief rationale 
Section 1.3 Schedule of Activities (SoA) 
Footnote x 
“Cycle 1 Day 1 2.5 hour samples 
must be collected at the scheduled 
time ±0.5 hour” was added 
To more specifically define the permitted 
sample collection window 
Section 1.1 Synopsis Objectives 
Section 3 STUDY OBJECTIVES AND 
PURPOSE Table 5 
Text was added to Part 2 Safety Run-
in Secondary Objective for general 
standard safety objective  
To ensure that all safety data were 
assessed in Part 2 Safety Run-in not just 
DLTs and events of Grade ≥3 
thrombocytopenia 
Throughout document 
Minor corrections and formatting 
adjustments were made 
To add clarification and increase 
readability 
 
 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 4 of 74 
TABLE OF CONTENTS 
1. 
PROTOCOL SUMMARY ............................................................................................8 
1.1. 
Synopsis ........................................................................................................................8 
1.2. 
Schemas ......................................................................................................................18 
1.3. 
Schedule of Activities (SoA) ......................................................................................18 
2. 
INTRODUCTION ......................................................................................................27 
2.1. 
Background .................................................................................................................27 
2.1.1. 
Background of Niraparib ............................................................................................27 
2.1.2. 
Background of Dostarlimab ........................................................................................27 
2.1.3. 
Rationale for Synergy Between PARP Inhibitors and Immune Checkpoint 
Inhibitors .....................................................................................................................27 
2.2. 
Rationale for Tumour Type ........................................................................................27 
2.3. 
Rationale for Current Study ........................................................................................27 
2.4. 
Rationale for the Primary Endpoint ............................................................................27 
2.5. 
Benefit Risk Assessment ............................................................................................28 
3. 
STUDY OBJECTIVES AND PURPOSE ..................................................................29 
4. 
INVESTIGATIONAL PLAN .....................................................................................32 
4.1. 
Overall Study Design ..................................................................................................32 
4.1.1. 
Dose Limiting Toxicity ...............................................................................................33 
4.2. 
Number of Participants ...............................................................................................35 
4.3. 
Treatment Assignment ................................................................................................35 
4.4. 
Dose Adjustment Criteria ...........................................................................................35 
4.4.1. 
Dose Adjustment Criteria for Age and Weight ..........................................................35 
4.4.2. 
Dose Adjustment for Adverse Events .........................................................................35 
4.4.3. 
Niraparib .....................................................................................................................35 
4.4.4. 
Dostarlimab .................................................................................................................38 
4.5. 
Criteria for Study Termination ...................................................................................38 
4.6. 
End of Study Definition ..............................................................................................38 
4.7. 
Study Conduct ............................................................................................................38 
4.7.1. 
Procedures by Visit .....................................................................................................38 
4.7.2. 
General Guidance for Treatment Continuity when Participants are Unable to 
Come into the Clinic ...................................................................................................38 
5. 
STUDY POPULATION .............................................................................................40 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 5 of 74 
5.1. 
Participant Inclusion Criteria ......................................................................................40 
5.2. 
Participant Exclusion Criteria .....................................................................................42 
5.3. 
Lifestyle Considerations .............................................................................................45 
5.4. 
Screen Failures ............................................................................................................45 
6. 
STUDY TREATMENT(S) AND CONCOMITANT THERAPY .............................46 
6.1. 
Study Treatment(s) Administered ...............................................................................46 
6.2. 
Preparation/Handling/Storage/Accountability ............................................................48 
6.2.1. 
Study Treatment Packaging and Labelling .................................................................48 
6.2.2. 
Study Treatment Storage ............................................................................................48 
6.2.3. 
Administration ............................................................................................................48 
6.2.4. 
Study Treatment Accountability .................................................................................48 
6.2.5. 
Study Treatment Handling and Disposal ....................................................................48 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................................48 
6.4. 
Study Treatment Compliance .....................................................................................48 
6.5. 
Dose Modification ......................................................................................................48 
6.6. 
Treatment of Overdose ...............................................................................................48 
6.7. 
Concomitant Therapy .................................................................................................48 
6.7.1. 
Rescue Medications ....................................................................................................49 
6.7.2. 
Prohibited Medications ...............................................................................................49 
6.7.3. 
Other Study Restrictions .............................................................................................49 
7. 
DISCONTINUATION OF STUDY TREATMENT AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................50 
7.1. 
Discontinuation of Study Treatment ...........................................................................50 
7.1.1. 
Liver Chemistry Stopping Criteria .............................................................................50 
7.1.2. 
QTc Stopping Criteria .................................................................................................50 
7.2. 
Withdrawal of Consent ...............................................................................................50 
7.3. 
Participant Discontinuation/Withdrawal from the Study ...........................................50 
7.4. 
Lost to Follow-Up.......................................................................................................50 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................51 
8.1. 
Assessment of Efficacy ...............................................................................................51 
8.1.1. 
Primary Efficacy Endpoint for the Osteosarcoma Cohort Expansion ........................51 
8.1.2. 
Secondary Efficacy Endpoints for the Osteosarcoma Cohort Expansion ..................51 
...........................................................51 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 6 of 74 
8.2. 
Assessment of Safety ..................................................................................................52 
8.2.1. 
Safety Parameters .......................................................................................................52 
8.3. 
Adverse Events and Serious Adverse Events .............................................................52 
8.4. 
Pharmacokinetics, Immunogenicity, and Biomarkers ................................................52 
.............................................................................................52 
.............................................................................................53 
8.6. 
Health Economics .......................................................................................................53 
9. 
STATISTICAL CONSIDERATIONS .......................................................................54 
9.1. 
Sample Size Determination ........................................................................................54 
9.2. 
Analysis Populations ..................................................................................................55 
9.3. 
Statistical Analyses .....................................................................................................56 
9.3.1. 
General Considerations ...............................................................................................56 
9.3.2. 
Primary Endpoints ......................................................................................................56 
9.3.3. 
Secondary Endpoints ..................................................................................................56 
....................................57 
....................................57 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................58 
11. 
APPENDICES ............................................................................................................59 
12. 
LIST OF REFERENCES ............................................................................................74 
 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 7 of 74 
LIST OF TABLES 
Table 1: 
Document History .........................................................................................................2 
Table 2 
List of main changes in the protocol and their rationale: .............................................2 
Table 3: 
Schedule of Activities .................................................................................................19 
Table 4: 
Tumour Assessment Flowchart ..................................................................................26 
Table 5: 
Objectives and Endpoints for Study 213406 Osteosarcoma Cohort ..........................29 
....................................................36 
Table 7: 
Niraparib Dose Modifications for Nonhaematologic Adverse Reactions ..................36 
Table 8: 
Niraparib Dose Modifications for Haematologic Adverse Reactions ........................37 
Table 9: 
Investigational Products ..............................................................................................47 
Table 10: Analysis Sets ...............................................................................................................55 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 8 of 74 
1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Name of Sponsor/Company: GSK 
Name of Investigational Product: Niraparib, dostarlimab 
Name of Active Ingredient: Niraparib, dostarlimab 
Title of Study: A Phase 1, Multicentre, Open-label, Dose escalation and Cohort Expansion Study of 
Niraparib and Dostarlimab in Paediatric Patients with Recurrent or Refractory Solid Tumours 
Part 2: Osteosarcoma Expansion Cohort 
Study Centre(s): Multicentre  
Phase of Development: 
Phase 1 
Objectives: 
The following are the objectives for the Safety Run-in Cohort and Osteosarcoma Expansion Cohort of 
this study. 
Part 2 Safety Run-in  
Primary: 
The primary objective of this cohort is as follows: 
• 
to assess the safety and tolerability of the 
 
 by assessing dose limiting toxicity (DLT) and Grade ≥3 
thrombocytopenia adverse events (AEs) in paediatric participants 
Secondary: 
The secondary objectives of this cohort are as follows: 
• 
to evaluate additional measures of anticancer activity, including objective response rate 
(ORR), duration of response (DOR), disease control rate (DCR), and progression-free 
survival (PFS) in paediatric participants 
• 
to characterise the pharmacokinetics (PK) of niraparib in paediatric participants 
• 
to evaluate the safety of the combination o
 
 in paediatric participants 
Part 2 Expansion 
Primary: 
The primary objective of this cohort is as follows: 
• 
to assess the antitumour activity of the combination of niraparib and dostarlimab, 
assessed primarily by the PFS rate at 6 months (PFS6) (using Response Evaluation 
Criteria in Solid Tumours [RECIST] v1.1 criteria) in paediatric participants. 
Secondary: 
The secondary objectives of this cohort are as follows: 
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 9 of 74 
• 
to evaluate additional measures of anticancer activity, including ORR, DOR, DCR, and 
PFS in paediatric participants 
• 
to evaluate the safety of the combination of 
 
 in paediatric participants 
• 
to characterise the pharmacokinetics (PK) of the combination of niraparib and 
dostarlimab in paediatric participants 
• 
to assess the immunogenicity of dostarlimab in paediatric participants 
• 
 
 
Methodology: 
The overall study design and conduct are described in the master protocol. 
 
 
 
 
  
Under Protocol Amendment 03, enrolment was paused 
 
 
 
 
 
 This modification is included in Protocol Amendment 05. 
 
 
 
 
 
. Study treatment may continue 
until progressive disease (PD), unacceptable toxicity, participant withdrawal, Investigator’s decision, 
or death. See Figure 1 for Part 2 study design. 
Under Protocol Amendment 05, enrolment in Part 2 will start with a Safety Run-in Cohort to confirm 
the safety, tolerability, and preliminary efficacy of the 
 
 in participants with osteosarcoma and neuroblastoma. A total of 8 DLT-evaluable 
participants will be enrolled in the Safety Run-in, with no more than 5 out of 8 evaluable participants 
having the same tumour type. Participants in the Safety Run-in will be observed for a minimum of 
42 days (2 cycles, DLT evaluation period) for DLTs and Grade≥3 thrombocytopenia. Participants in 
the Safety Run-in will be dosed in a staggered fashion, meaning no more than 3 participants will be 
allowed to receive study treatment until each dosed participant has completed at least 2 cycles of 
study treatment and the resulting data from all 3 dosed participants have been reviewed. This is to 
ensure an adequate interval for observation and assessment of tolerability of the 
  
• 
If DLTs or Grade ≥3 thrombocytopenia are observed in ≤1 participant out of the first 3 dosed 
participants and it is deemed safe to proceed by the study team, additional participants will be 
enrolled for up to 8 DLT-evaluable participants. 
CCI
CCI
CCI
CCI
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 10 of 74 
• 
If DLTs or Grade ≥3 thrombocytopenia are observed in ≥2 participants out of the first 3 
dosed participants, the Part 2 Safety Run-in Cohort will be paused. Review of safety data and 
available PK data and determination of the dosing strategy for subsequent participants will be 
completed by the Dose Escalation Committee (DEC; see Appendix 1 of the master protocol 
for details regarding the DEC). 
• 
The Part 2 Expansion Cohort will be initiated if 2 or less DLTs and 2 or less Grade ≥3 
thrombocytopenia events are observed out of 8 DLT-evaluable participants. 
• 
The Safety Run-in will be paused if 2 or less DLTs and 3 Grade ≥3 thrombocytopenia events 
are observed out of 8 DLT-evaluable participants. 
• 
If DLTs are observed in 3 of 8 participants or Grade ≥3 thrombocytopenia is observed in 4 of 
8 participants, 
 
 in the Safety Run-in Cohort would be considered intolerable.  
Once all participants in the Safety Run-in have been observed for ≥42 days, all available data from 
the Part 2 Safety Run-in together with all data previously collected under Protocol Amendment 04 or 
earlier, will be reviewed by the study DEC and the Data Review Committee (DRC) before additional 
participants on Part 2 are enrolled.  
Further details are provided in protocol Section 4.1, including details of the DLTs.  
Following the Safety Run-in, if the 
 is deemed safe, up to 
30 evaluable participants may enrol in the Part 2 Cohort Expansion for osteosarcoma, inclusive of any 
eligible participants with osteosarcoma treated in the Part 2 Safety Run-in. Enrolment into the Part 2 
Cohort Expansion will be conducted according to a Simon’s 2-stage optimal design in which ≥2 of 
the first 10 evaluable participants must achieve PFS6 before accrual of the remaining 20 participants. 
 
 
 
 
 
 
  
 
 
General study conduct is described in the master protocol. 
 
 
 
 
Data Review Committee 
A DRC will be established for the purpose of monitoring safety and efficacy data from the Safety 
Run-in and cohort expansion part of the study (Part 2). This committee will be composed of GSK 
staff who are independent of all aspects of the study. Members will include a clinical development 
physician, a safety physician, and a statistician. This committee will convene both periodically and on 
an ad hoc basis, as mandated by emerging study data. Comprehensive details of committee 
membership and its activities will be described in a formal charter. 
Number of Participants (Planned): Safety Run-in: approximately 8 DLT-evaluable participants in 
total across osteosarcoma (Part 2A) and neuroblastoma (Part 2B).  
Part 2 Expansion: approximately 30 participants with osteosarcoma are planned for enrolment in this 
cohort (including eligible participants with osteosarcoma from the Safety Run-in). See Section 9.1 for 
eligibility requirements for enrolment of Safety Run-in participants into Part 2 Cohort Expansion. 
CCI
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 11 of 74 
Diagnosis and Main Criteria for Inclusion: 
Participant will be eligible for the Safety Run-in and the Osteosarcoma Expansion Cohorts of Part 2 if 
all of the following criteria are met: 
1. 
 
 
 
2. Participant with osteosarcoma has radiologically measurable disease at screening that can be 
tracked as RECIST v1.1 target lesion(s). 
5. Performance status must be ≥60% on the Karnofsky scale for participants >16 years of age 
and ≥60% on the Lansky scale for participants ≤16 years of age. 
Note: Neurologic deficits in participants with brain metastases must have been stable for at 
least 7 days prior to study enrolment. Participants who are unable to walk because of 
paralysis, but who are upright in a wheelchair, will be considered ambulatory for the purpose 
of assessing the performance status. 
6. Participant has adequate organ function, defined as follows: 
Note: The participant must not have received blood transfusion, growth factors, or platelet 
stimulating agents in the 14 days prior to providing a sample for haematologic analysis nor 
erythropoietin in the prior 6 weeks. 
a. absolute neutrophil count ≥1000/μL 
b. platelets ≥100 000/μL 
c. haemoglobin ≥8 g/dL or ≥5.0 mmol/L 
d. serum creatinine≤1.5×upper limit of normal (ULN) for age or calculated creatinine 
clearance or radioisotope glomerular filtration rate ≥60 mL/min/1.73m2 
e. total bilirubin ≤1.5× ULN or direct bilirubin ≤1 × ULN 
f. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN 
unless liver metastases are present, in which case AST and ALT must be ≤5 × ULN 
g. international normalised ratio or prothrombin time (PT) ≤1.5 × ULN unless the 
participant is receiving anticoagulant therapy, as long as PT or partial thromboplastin 
time (PTT) is within therapeutic range of intended use of anticoagulants 
h. activated PTT ≤1.5 × ULN unless the participant is receiving anticoagulant therapy, 
as long as PT or PTT is within therapeutic range of intended use of anticoagulants 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 12 of 74 
7. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at 
least one of the following conditions applies: 
a. Is not a woman of childbearing potential (WOCBP). 
or 
b. 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 3 of the master protocol, from the Screening Visit through at least 180 days 
after the last dose of study treatment and agrees not to donate eggs (ova, oocytes) for 
the purpose of reproduction during this period. The Investigator should evaluate the 
effectiveness of the contraceptive method in relationship to the first dose of study 
treatment. 
c. A WOCBP must have a negative highly sensitive pregnancy test (urine or serum, as 
required by local regulations) within 24 hours prior to the first dose of study 
treatment and irrespective of prior medical treatment. 
Additional requirements for pregnancy testing during and after the Treatment Period are in 
the master protocol. 
The Investigator is responsible for review of medical history, menstrual history, and recent 
sexual activity to decrease the risk for inclusion of a woman with an early undetected 
pregnancy. 
8. A male participant of reproductive potential is eligible to participate if he agrees to the 
following starting with the first dose of study treatment through at least 90 days (a 
spermatogenesis cycle) after the last dose of study treatment: 
a. refrain from donating sperm 
plus, either: 
b. be abstinent from heterosexual intercourse as their preferred and usual lifestyle 
(abstinent on a long-term and persistent basis) and agree to remain abstinent 
or 
c. must agree to use a male condom and should also be advised of the benefit for a 
female partner to use a highly effective method of contraception, as a condom may 
break or leak, when having sexual intercourse with a WOCBP who is not currently 
pregnant. 
9. The Investigator, or a person designated by the Investigator, will obtain written informed 
consent from each study participant or the participant’s legally acceptable representative, 
parent(s), or legal guardian and the participant’s assent, when applicable, before any study-
specific activity is performed. The Investigator will retain the original copy of each 
participant’s signed consent/assent document. 
10. 
 
 
 
 
 
 
 
 
 
 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 13 of 74 
Main Criteria for Exclusion: 
Participant will not be eligible for study entry if any of the following criteria are met: 
1. Participation presents unacceptable risk to the prospective participant based on the 
Investigator’s judgement. 
2. Participant has known hypersensitivity to dostarlimab or niraparib, their components, or their 
excipients. 
3. Participant has received prior therapy with an anti-PD-1, anti-programmed cell death-
ligand 1, anti-programmed cell death-ligand 2, anticytotoxic T-lymphocyte-associated 
antigen-4 antibody (including ipilimumab), or any other antibody or drug specifically 
targeting T-cell co-stimulation or checkpoint pathways (with the exception of participants 
rolling over from Part 1 of the study: these participants are allowed to have received 
dostarlimab). 
4. Participant has had prior treatment with a known PARP inhibitor (with the exception of 
participants rolling over from Part 1 of the study: these participants are allowed to have 
received niraparib). 
5. Participant has a known history of myelodysplastic syndrome or acute myeloid leukaemia. 
6. Participant has active autoimmune disease that has required systemic treatment in the past 
2 years (i.e., with use of disease-modifying antirheumatic drugs, corticosteroids, or 
immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic 
corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a 
form of systemic treatment. 
7. Participant has known active central nervous system metastases, carcinomatous meningitis, or 
both. Note: Participants with previously treated brain metastases may participate provided 
they are clinically stable and have no evidence of new, enlarging, or progressing brain 
metastases (using the identical imaging modality for each assessment, either MRI or CT scan) 
for at least 4 weeks (28 days) prior to the first dose of study treatment. In addition, the 
participant must not have been using steroids for at least 7 days prior to the first dose of study 
treatment. Carcinomatous meningitis precludes a participant from study participation 
regardless of clinical stability. 
8. Participant had a known additional (second primary) malignancy that progressed or required 
active treatment within the last 2 years. 
9. Participant is considered a poor medical risk due to a serious, uncontrolled medical disorder, 
nonmalignant systemic disease, or active infection that requires systemic therapy. Specific 
examples include, but are not limited to, history of (noninfectious) pneumonitis that required 
steroids or current pneumonitis, uncontrolled ventricular arrhythmia, uncontrolled major 
seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any 
psychiatric or substance abuse disorders that would interfere with cooperation with the 
requirements of the study (including obtaining assent/consent). 
10. Participant has a condition (such as transfusion-dependent anaemia or thrombocytopenia), 
requirement for therapy, or laboratory abnormality that might confound the study results or 
interfere with the participant’s participation for the full duration of the study treatment. 
11. Participant is pregnant, breastfeeding, or expecting to conceive within the projected duration 
of the study, starting with the Screening Visit through 180 days after the last dose of study 
treatment. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 14 of 74 
No data are available regarding the presence of dostarlimab or niraparib or its metabolites in 
human milk, or on its effects on the breastfed infant or milk production. Because of the 
potential for serious adverse reactions in breastfed infants from dostarlimab and/or niraparib, 
female participants should not breastfeed during treatment with dostarlimab and/or niraparib 
and for at least 4 months after the last dose of dostarlimab or at least 30 days after the last 
dose of niraparib, whichever is longer.  
12. Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or 
any other form of immunosuppressive therapy within 7 days prior to the first dose of study 
treatment. 
13. Participant has a known history of HIV (type 1 or 2 antibodies). 
14. Participant has documented presence of HbsAg and/or HBcAb at Screening or within 
3 months prior to first dose of study intervention. Participants with a negative HbsAg and 
positive HbcAb result are eligible only if HBV DNA is negative (Appendix 12 of the master 
protocol) 
15. Participant must not have a gastrointestinal condition, such as bowel obstruction, that can 
impact absorption of oral medications and is identified by clinical symptoms or CT scan, etc. 
16. Participant has had any known Grade 3 or 4 anaemia, neutropenia, and/or thrombocytopenia 
that was related to the most recent prior anticancer treatment and that persisted >4 weeks 
(28 days). 
17. Participant has not recovered (i.e., to Grade ≤1 or to baseline) from prior systemic therapy-
induced AEs. Note: Participants with alopecia, hearing impairment, Grade ≤2 neuropathy, 
Grade ≤2 fatigue, Grade ≤2 anaemia, and/or Grade ≤2 neutropenia are an exception to this 
criterion and may qualify for participation in the study. 
18. Participant had toxicity related to prior immunotherapy that led to treatment discontinuation. 
19. Participant had treatment with systemic anticancer therapy (investigational agent or device, or 
approved chemotherapy, targeted therapy, immunotherapy, or other systemic therapy) within 
the 3 weeks or 5 half-lives, whichever is shorter, prior to the first dose of study treatment; 
radiation therapy encompassing >20% of the bone marrow within 2 weeks prior to the first 
dose of study treatment, or any radiation therapy within 1 week prior to the first dose of study 
treatment. 
20. Participant has not recovered adequately from AEs or complications from any major surgery 
prior to starting study treatment. 
21. Participant has received a live vaccine within 30 days of planned start of study treatment. 
22. Participant has clinically significant cardiovascular disease (eg, significant cardiac conduction 
abnormalities, uncontrolled hypertension, cardiac arrhythmia or unstable angina, New York 
Heart Association Grade 2 or greater congestive heart failure, serious cardiac arrhythmia 
requiring medication, and history of cerebrovascular accident) within 6 months of enrolment. 
23. Participant has heart rate-corrected QT interval prolongation at Screening >450 msec or 
>480 msec for participants with bundle branch block. 
Notes: 
• 
The QTc is the QT interval corrected for heart rate according to Bazett’s formula 
(QTcB), Fridericia’s formula (QTcF), and/or another method, machine read or 
manually over read. 
• 
The specific formula that will be used to determine eligibility and discontinuation for 
an individual participant must be determined prior to initiation of the study and used 
consistently for eligibility and study assessments. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 15 of 74 
24. Participant has received a solid organ transplant. 
25. Participant has a documented presence of HCV antibody at Screening or within 3 months 
prior to first dose of study intervention. NOTE: Participants with a positive HCV antibody 
test result due to prior resolved disease can be enrolled, only if a confirmatory HCV RNA test 
is negative and the participant otherwise meets entry criteria. 
26. Participant has a documented presence of HCV RNA at Screening or within 3 months prior to 
first dose of study intervention. NOTE: The HCV RNA test is optional and participants with 
negative HCV antibody test are not required to undergo HCV RNA testing as well. 
Investigational Product, Dosage, and Mode of Administration: 
. Oral niraparib will be dispensed to 
participants on Day 1 of every 21-day treatment cycle beginning with Cycle 1 of the Treatment 
Period. 
 
  
A summary of study treatment administration is provided in the master protocol, and details are in the 
Pharmacy Manual. 
Duration of Treatment: Study treatment may continue until documented PD, unacceptable toxicity, 
participant withdrawal, Investigator’s decision, or death. 
Reference Therapy, Dosage, and Mode of Administration: 
Not applicable. 
Criteria for Evaluation: 
Part 2 Safety Run-in 
• 
DLTs during the first 42 days following the initiation of study treatment (i.e., approximately 
the first 2 treatment cycles). 
• 
Thrombocytopenia Grade ≥3 AEs during the first 42 days following initiation of study 
treatment (i.e., approximately the first 2 treatment cycles). 
• 
ORR is defined as the proportion of participants who have a best overall response (BOR) of 
confirmed complete response (CR) or partial response (PR) as determined by the Investigator 
using International Neuroblastoma Response Criteria (INRC) for participants with 
neuroblastoma or RECIST v1.1 for participants with osteosarcoma. 
• 
DOR is defined as the time from first documentation of confirmed response (CR or PR) until 
the time of first documented PD by RECIST v1.1 or INRC for participants with 
neuroblastoma or RECIST v1.1 for participants with osteosarcoma based on Investigator 
assessment or death (whichever occurs first). 
• 
DCR is defined as the proportion of participants who have achieved a BOR of confirmed CR, 
confirmed PR, or stable disease by INRC for participants with neuroblastoma or RECIST 
v1.1 for participants with osteosarcoma based on Investigator assessment. 
• 
PFS is defined as the time from the date of the first dose of study treatment to the first 
documented PD, as determined by INRC for participants with neuroblastoma or RECIST v1.1 
for participants with osteosarcoma based on Investigator assessment, or death from any cause 
(whichever occurs first). 
 
 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 16 of 74 
Part 2 Efficacy 
• 
PFS6, defined as the proportion of participants without PD per RECIST v1.1 criteria or death 
at 6 months from the date of the first dose of study treatment. 
• 
ORR, defined as the proportion of participants who have a BOR of confirmed CR or PR as 
determined by the Investigator using RECIST v1.1. 
• 
DOR, defined as the time from first documentation of confirmed response (CR or PR) until 
the time of first documented PD by RECIST v1.1 based on Investigator assessment or death 
(whichever occurs first). 
• 
DCR, defined as the proportion of participants who have achieved a BOR of confirmed CR, 
confirmed PR, or stable disease by RECIST v1.1 based on Investigator assessment. 
• 
PFS, defined as the time from the date of the first dose of study treatment to the first 
documented PD, as determined by RECIST v1.1 based on Investigator assessment, or death 
from any cause (whichever occurs first). 
The criteria for evaluation of safety, PK, palatability of niraparib, and antidrug antibodies of 
dostarlimab are described in the master protocol. 
Statistical Methods: 
Sample Size Consideration 
Part 2 Safety Run-In  
The statistical gating to initiate the Part 2 Cohort Expansion will be based on minimum of 8 DLT-
evaluable participants for DLTs across osteosarcoma and neuroblastoma. When 2 or less DLTs and 2 
or less Grade ≥3 thrombocytopenia AEs are observed, the study will continue to Part 2 Cohort 
Expansion. When 3 or more DLTs are observed, the study may not continue to Part 2 Cohort 
Expansion. When 2 or less DLTs and 3 out of 8 Grade ≥3 thrombocytopenia AEs are observed, the 
study may be paused for data review. If there is a differential in the DLT-evaluable number of 
participants to 8 for either endpoint, other criteria may apply and will be specified in the SAP. This 
will be the primary guideline for the dose recommendations; the totality of data will be taken into 
account. The probability of initiating Part 2 Cohort Expansion and the probability of pausing for data 
review are presented in Section 9.1 for 8 DLT-evaluable participants, assuming a weak correlation of 
0.15 between the 2 endpoints. 
Part 2 Cohort Expansion 
The sample size for this cohort is based on a Simon’s 2-stage optimal design, with a 1-sided alpha of 
0.05 and a minimum power of 80%. The null hypothesis is ≤10% PFS6, and the alternative 
hypothesis is ≥30% PFS6. A futility analysis will be performed after the initial assessment of 
response for 10 participants in the cohort. If, among the 10 mITT participants in the cohort, at least 
2 participants remain progression-free after 6 months, an additional 19 mITT participants will be 
enrolled. If 6 or more participants out of the 29 participants remain progression-free after 6 months, 
the null hypothesis will be rejected. The required sample size of 29 is based on the modified Intent-to-
Treat (mITT) Population. The total sample size to be enrolled is planned at approximately 30 in case 
of the potential lack of sufficient participants in the mITT Population. For consideration of futility, 
those Part 1 participants who satisfy the inclusion and exclusion criteria of Part 2, satisfy the mITT 
Population definition, and are treated at the dose used in Part 2 will be included in the Part 2 efficacy 
analysis and will be counted in the required Part 2 Cohort Expansion sample size. Under Protocol 
Amendment 05, osteosarcoma Safety Run-in participants who satisfy the mITT Population definition 
and are treated at the dose used in the Part 2 Cohort Expansion will also be included in the Part 2 
Cohort Expansion efficacy analysis and will be counted in the required Part 2 Cohort Expansion 
sample size. The software for the sample size calculation is PASS 2019 (NCSS). 
 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 17 of 74 
Analysis Populations 
• 
The DLT-evaluable Population consists of participants in Part 2 Safety Run-in who complete 
the DLT observation period through at least 2 cycles of study treatment (including ≥80% of 
the intended niraparib dose and ≥2 infusions of dostarlimab) or experience a DLT for DLT 
endpoint (or Grade ≥3 thrombocytopenia AEs for the thrombocytopenia endpoint).  
• 
The Safety Population is defined as all participants who receive at least 1 dose of either 
niraparib or dostarlimab. 
• 
The Intent-to-Treat Population includes all participants who receive any study medication and 
have measurable baseline tumour assessment. 
• 
The mITT Population includes all participants who receive any study medication, have 
measurable baseline tumour assessment, and have at least 1 postbaseline tumour assessment. 
• 
The Per-Protocol Population includes all participants in the mITT Population who do not have 
protocol violations during the study that may significantly impact the interpretation of 
efficacy results. 
• 
The PK Population includes all participants who receive at least one dose of study treatment 
and have at least one PK sample. PK Populations are defined separately for each agent. 
• 
Immunogenicity (ADA) Population includes all participants who receive at least 1 dose of 
dostarlimab and who have at least 1 ADA sample with a result. 
General Methods 
An overall description of the statistics for this study is provided in the master protocol. Additional 
details are provided in the Statistical Analysis Plan. 
Efficacy Analysis 
All analyses will include summary statistics, including number of participants and percentage for 
categorical variables and number of participants, mean, standard deviation, median, minimum, and 
maximum for continuous variables. Two-sided exact 95% CIs based on the Clopper-Pearson method 
will be provided where appropriate (Clopper, 1934). Time-to-event analyses will be performed using 
Kaplan-Meier methods. 
The primary analysis set for the efficacy endpoints will be the mITT Population. 
PFS6 and its 2-sided 95% CI will be estimated using the Clopper-Pearson method. 
The number and proportion of participants with an objective response will be tabulated. ORR and 
DCR will be calculated, along with their estimated 2-sided 95% CI. Among the participants with a 
confirmed response, a time-to-event analysis of DOR will be performed using Kaplan-Meier methods, 
including quartile estimates and 2-sided 95% CI. PFS and its 2-sided 95% CI will be estimated using 
the Kaplan-Meier method. 
 
 
 
 
 
  
Safety, PK, Immunogenicity, 
 
These analyses are described in the master protocol. 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 18 of 74 
1.2. 
Schemas 
Refer to the master protocol for the overall study schema.  
Figure 1: 
Part 2 Study Design 
 
Abbreviations CR=complete response; PFS6=progression-free survival at 6 months; PR=partial response. 
1.3. 
Schedule of Activities (SoA) 
The schedule of activities (SoA) for this cohort is provided in Table 3. The tumour assessment 
flowchart is presented in Table 4.The study will be conducted in conformance with the protocol, 
Good Clinical Practice (GCP), and applicable regulatory requirements. Regulatory, ethical, and 
study oversight considerations are provided in Appendix 1 of the master protocol. 
 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05  
Page 19 of 74 
Table 3: 
Schedule of Activities 
Protocol Activity 
Screening 
Period 
Treatment Period 
EOT 
Visit a,b 
Safety FUP 
Visit 
(30 [+7] Days 
Post-
Treatment) b 
FUP Assessment 
Period 
(Every 90 [±14] Days 
Post-Treatment) c 
Study treatment cycle 
 
Cycles 1-2 
Cycles 3+ 
 
 
 
Cycle week 
 
1 
2 
3 
1 
2 
 
 
 
Study day 
-28 to -1 
 
 
 
 
 
 
 
 
Study visit window 
(days within cycle) 
 
±3 
±3 
±3 
±3 
±3 
+7 
+7 
±14 
Procedure 
 
 
 
 
 
 
 
 
 
Informed consent/assentd 
X 
 
 
 
 
 
 
 
 
Demographics and 
medical history 
X 
 
 
 
 
 
 
 
 
Performance status 
X 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
X 
 
 
 
 
 
 
 
 
Physical examination 
X 
A complete physical examination is to be conducted at Screening and EOT only, and 
as clinically indicated. 
 
 
Psychological 
assessmentsf 
X 
 
 
 
 
 
X 
 
 
Vital signs, weight, and 
height g 
X 
X 
X 
X 
X 
X (Cycle 3 
only) 
X 
X 
X 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05  
Page 20 of 74 
Protocol Activity 
Screening 
Period 
Treatment Period 
EOT 
Visit a,b 
Safety FUP 
Visit 
(30 [+7] Days 
Post-
Treatment) b 
FUP Assessment 
Period 
(Every 90 [±14] Days 
Post-Treatment) c 
Study treatment cycle 
 
Cycles 1-2 
Cycles 3+ 
 
 
 
Cycle week 
 
1 
2 
3 
1 
2 
 
 
 
Study day 
-28 to -1 
 
 
 
 
 
 
 
 
Study visit window 
(days within cycle) 
 
±3 
±3 
±3 
±3 
±3 
+7 
+7 
±14 
Procedure 
 
 
 
 
 
 
 
 
 
CBC with differential h 
X 
X 
(Twice 
weekly for 
Safety Run-
in only) 
X 
(Twice 
weekly for 
Safety Run-
in only) 
X 
(Twice 
weekly for 
Safety Run-
in only) 
X 
 
X 
 
 
Coagulation h 
X 
As clinically indicated 
X 
 
 
Blood chemistry h 
X 
X 
X 
X 
X 
 
X 
 
 
Serum or urine 
pregnancy test (WOCBP 
only) i  
X 
X 
 
 
X 
 
X 
X 
X 
12-lead ECG k 
X 
 
 
 
X (Cycle 3 
only) 
 
X 
 
 
Dostarlimab 
administration 
 
X 
 
 
X 
 
 
 
 
Niraparib 
dispensed/collected 
(administered Day 1 
after dostarlimab 
infusion) 
 
X 
 
 
X 
 
X 
(Collect-
ion only) 
 
 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05  
Page 21 of 74 
Protocol Activity 
Screening 
Period 
Treatment Period 
EOT 
Visit a,b 
Safety FUP 
Visit 
(30 [+7] Days 
Post-
Treatment) b 
FUP Assessment 
Period 
(Every 90 [±14] Days 
Post-Treatment) c 
Study treatment cycle 
 
Cycles 1-2 
Cycles 3+ 
 
 
 
Cycle week 
 
1 
2 
3 
1 
2 
 
 
 
Study day 
-28 to -1 
 
 
 
 
 
 
 
 
Study visit window 
(days within cycle) 
 
±3 
±3 
±3 
±3 
±3 
+7 
+7 
±14 
Procedure 
 
 
 
 
 
 
 
 
 
Tumour assessment: 
CT or MRI l,m 
Xn,o 
Every 9 weeks (every 63 [±7] days) following the start of study treatment 
for the first 12 months and then every 12 weeks (every 84 [±7] days) 
thereafter, or more frequently if clinically indicated, until documented PD, 
the start of alternative anticancer, or discontinuation from overall study 
participation (e.g., death, participant’s request, or participant is lost to 
follow-up), whichever comes firstp 
Xq 
Tumour assessment: 
Bone scan, whole body 
MRI, or PET scan m, r  
Xo 
Required throughout this interval if clinically indicated and to confirm disease response if baseline scan was positive for metastatic 
bone disease 
AE monitoring u 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Prior and concomitant 
medications and nondrug 
treatments 
X 
Medications and nondrug treatments will be monitored for study purposes from Screening to at least 
30 days following the last dose of study treatment 
 
Blood sample for 
dostarlimab PK and/or 
ADAs and neutralising 
antibodies v, w  
 
X 
X (Cycle 1 
only) 
 
X (predose, 
Cycles 4 
and 6, and 
every 6 
cycles 
thereafter) 
 
X 
X 
X 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05  
Page 22 of 74 
Protocol Activity 
Screening 
Period 
Treatment Period 
EOT 
Visit a,b 
Safety FUP 
Visit 
(30 [+7] Days 
Post-
Treatment) b 
FUP Assessment 
Period 
(Every 90 [±14] Days 
Post-Treatment) c 
Study treatment cycle 
 
Cycles 1-2 
Cycles 3+ 
 
 
 
Cycle week 
 
1 
2 
3 
1 
2 
 
 
 
Study day 
-28 to -1 
 
 
 
 
 
 
 
 
Study visit window 
(days within cycle) 
 
±3 
±3 
±3 
±3 
±3 
+7 
+7 
±14 
Procedure 
 
 
 
 
 
 
 
 
 
Blood sample for 
niraparib PK w,x 
 
X (Cycles 1 
and 2 only) 
X (Cycle 1 
only) 
 
 
 
 
 
 
Alternative anticancer 
treatment assessment 
 
 
 
 
 
 
X 
X 
X 
Abbreviations: ADA=antidrug antibody; AE=adverse event; AESI=adverse event of special interest; ALP=alkaline phosphatase; BP=blood pressure; 
 
CBC=complete blood count; CNS=central nervous system; CR=complete response; CT=computed tomography; ECG=electrocardiogram; eCRF=electronic case report form; 
EOT=End of Treatment; FUP=follow-up; G-CSF=granulocyte-colony stimulating factor; HbcAb=hepatitis B core antibody; HbsAg=hepatitis B surface antigen; 
HCVAb=Hepatitis C virus antibody; IV=intravenous; MRI=magnetic resonance imaging; PD=progressive disease; PET=positron emission tomography; PK=pharmacokinetics; 
PR=partial response; RECIST=Response Evaluation Criteria in Solid Tumours; SAE=serious adverse event; WOCBP=woman of childbearing potential. 
a. 
All participants will undergo an EOT Visit no more than 7 days following the decision to discontinue study treatment for any reason. 
b. 
The Safety FUP Visit and EOT Visit can be combined if both fall within the same window. The Safety FUP Visit is to take place no sooner than 30 days after last dose to 
permit the protocol-required collection of AEs/SAEs occurring during this 30-day interval. The Safety FUP Visit has a window of +7 days. 
c. 
During the FUP Assessment Period, participants will be followed via clinic visit or telephone contact every 90 (±14) days after the last dose of study treatment for the first 
year, every 180 (±14) days for the subsequent 2 years, and yearly (±14 days) for an additional 2 years (5 years total), or until the start of alternative antitumour therapy 
(unless there is an ongoing AE/SAE that must be followed until resolved, stabilised, or otherwise explained), the participant withdraws from the study overall, is lost to follow-
up, or dies (whichever occurs earlier). 
d. 
Informed consent/assent must be obtained prior to undergoing any study-specific procedure and may occur prior to the 28-day Screening Period. 
e. 
 
 
 
f. 
Psychological assessments to be performed as per local standard of care. 
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05  
Page 23 of 74 
g. 
Vital signs include temperature, blood pressure, heart rate, and respiratory rate. Vital signs will be taken before, every 15 to 30 minutes during, and at the end of every 
dostarlimab infusion. Throughout the Treatment Period, all vital signs will be monitored at Week 1 of each cycle even if dostarlimab is not administered. In addition, for the 
first 8 weeks of the Treatment Period (up to and including Cycle 3 Week 2), all vital signs will be monitored at Week 2 and Week 3 of each cycle. Height and weight will be 
measured at Screening, Day 1 of each cycle, EOT, 30-day Safety Follow-up, and during the FUP Assessment Period. 
h. 
Haematology, coagulation, and chemistry assessments will be performed by local laboratories. Parameters required in this study are listed in the master protocol. 
Haematology and chemistry assessments must be measured within 7 days prior to Cycle 1 Day 1 to confirm eligibility. Haematology must be performed and results evaluated 
prior to study treatment administration. Haematology is to be checked twice each week during the first 2 cycles of study treatment for participants enrolled in Part 2 Safety 
Run-in and once weekly for participants enrolled in Part 2 Osteosarcoma Expansion Cohort. Haematology tests may be performed at a laboratory facility other than the study 
site, but the test results must be reported to the study site, the study site must keep a copy of test results with the participant’s study file, and the results must be entered into 
the eCRF. If dose interruption or modification is required at any point on study because of haematologic toxicity, weekly blood draws for CBC will be done according to 
Table 8. Additional haematology or chemistry assessments may be performed according to local standard of care or as clinically indicated. If Cycle 1 Day 1 is no more than 
7 days following sample collection for Screening, these samples do not need to be collected again for Cycle 1 Day 1, unless clinically warranted. Additional monitoring for 
haematology is to be performed after a niraparib dose increase due to a birthday or due to a weight increase that moves participants to a higher 
 
, respectively. Haematology is to be checked twice each week during the first 2 cycles after the niraparib dose increase for participants enrolled in the Part 2 Safety 
Run-in and once weekly for participants enrolled in the Part 2 Osteosarcoma Expansion Cohort. Blood samples should be collected in order of priority as outlined in 
Section 8.2 
i. 
If the participant is a WOCBP, urine or serum pregnancy test will be performed by the local laboratory at the Screening Visit, within 24 hours prior to the first dose of study 
treatment, on Day 1 of every cycle for the duration of the Treatment Period, at the EOT Visit, at the 30-Day Safety Follow-up Visit, and 180 (±14) days after the last dose of 
study treatment. Pregnancy testing should occur irrespective of prior medical treatment. The results from these tests must be available and negative before study treatment is 
administered. Additional pregnancy testing may be necessary if required by local practices or regulations or if potential pregnancy is suspected. 
j. 
 
 
k. 
ECG should be repeated at Cycle 3 Week 1 and EOT, as well as during the Treatment or FUP Periods if clinically indicated. 
l. 
CT scans should be performed with contrast agents unless contraindicated for medical reasons. MRI of the abdomen and pelvis can be substituted for CT if MRI adequately 
depicts the disease. However, MRI of the chest should not be substituted for CT of chest even if IV contrast is contraindicated. In such a case, CT will be performed without 
contrast to evaluate the lung parenchyma. If MRI is used to follow-up bone lesion(s), it must be performed prior to any treatment that may affect bone marrow cellularity (eg, 
G-CSF). PET/CT may be used according to RECIST v1.1 guidelines with full-dose diagnostic CT and as clinically indicated. 
m. The same imaging technique/modality must be used to follow identified lesions throughout the study for a given participant. Clinical assessment of superficial lesions should 
be carried out on the same date as the imaging studies or no later than 3 days thereafter and must be recorded in the participant’s eCRF. 
n. 
Participants must have a baseline tumour assessment (CT or MRI) of the chest, abdomen, pelvis, and any additional sites as clinically indicated within 28 days prior to the 
first dose of study treatment. A baseline brain scan (IV contrast-enhanced MRI [preferred] or IV contrast-enhanced CT scan) is required for participants with previously 
treated brain metastases. Participants with previously treated brain metastases may participate under the conditions detailed in Exclusion Criterion 7. 
o. 
Radiologic assessments obtained per the standard of care prior to enrolment into the study do not need to be repeated and are acceptable to use as baseline evaluations, if 
all of the following conditions are met:  
(1) the CT or MRI tumour assessments were obtained within 28 days prior to the first dose of study treatment/the bone scan, whole body MRI, or PET tumour 
assessments were obtained within 84 days prior to the first dose of study treatment,  
(2) the assessments were performed using the method requirements outlined in RECIST v1.1,  
(3) the same imaging technique/modality must be used to follow identified lesions throughout the study for a given participant, and  
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05  
Page 24 of 74 
(4) appropriate documentation indicating that these radiologic tumour assessments were performed as standard of care is available in the participant’s source notes. 
p. 
Tumour assessments by CT or MRI of sites involved by disease at baseline and of any additional sites as clinically indicated will be done postbaseline (see Table 4). Tumour 
assessments should be conducted as outlined in Table 3. Tumour assessments should be scheduled using the date of the first dose of study treatment as the reference date 
for all time points and are not to be scheduled based on the date of the previous imaging time point. Imaging assessment delay to conform to study treatment delay is not 
permitted.  
q. 
Participants who have already demonstrated documented PD as per RECIST v1.1 do not need to have tumour assessments repeated at the EOT Visit or during the Post-
Treatment FUP. Participants who do not have documented PD at time of study treatment discontinuation; will continue to undergo tumour assessments on their original 
schedule (i.e., every 9 weeks [every 63 ±7 days] from the start of study treatment for the first 12 months and then every 12 weeks [every 84 ±7 days] thereafter until 
documented PD, start of alternative anticancer treatment, or discontinuation from overall study participation [eg, death, participant’s request, or participant is lost to follow-up], 
whichever comes first). Participants who have a PR or CR while on treatment and discontinue treatment prior to the next disease assessment must have all appropriate 
follow-up disease assessments to confirm the observed response no sooner than 4 weeks (28 days) after the first observation. 
r. 
Bone scan, whole body MRI, or PET scans will be carried out at baseline for all participants with osteosarcoma within 84 days prior to the first dose of study treatment in 
order to detect bony sites of disease. Subsequent assessments are to be performed during the Treatment Period when clinically indicated (i.e., participant describes new or 
worsening bone pain, or other signs or symptoms of new/progressing bone metastases are present). If the baseline bone scan, whole body MRI, or PET scan is positive for 
metastatic bone disease, a repeat assessment is required for confirmation of PR or CR.  
s. 
(Footnote intentionally left blank.) 
t. 
Only at Cycle 1 Week1 and Cycle 1 Week 2 for participants who receive 
 niraparib tablets and those who receive 
  
u. 
AEs will be collected until 30 days after the last dose of study treatment. SAEs will be collected until 90 days after the last dose of study treatment (or to a minimum of 
30 days after the last dose of study treatment if the participant starts alternative anticancer treatment). However, any SAEs assessed as related to study participation or 
related to study treatment will be recorded through the FUP Assessment Period. AESIs must be recorded on the eCRF. AESI collection periods are described in the master 
protocol. Any pregnancies that occur in female participants within 180 days after the last dose of study treatment or in partners of male participants within 90 days after the 
last dose of study treatment are to be reported as described in the master protocol. Pregnancies occurring more than 180 days after last dose of study treatment with an 
associated SAE (considered causally related to the study treatment by the Investigator) will follow the SAE reporting requirements. All AEs and SAEs will be followed, 
regardless of start of alternative anticancer therapy, until the event is resolved, stabilised, or otherwise explained; or until the participant has withdrawn consent to the study 
overall, is lost to follow-up (as defined in the master protocol), or has died. 
v. 
Blood samples (single sample for all analytes) for serum dostarlimab PK and/or ADA and neutralising antibodies (NAb) will be collected from participants during Cycle 1 at the 
following time points relative to the start of the dostarlimab infusion: Cycle 1 Day 1 at Predose (PK, ADA, and NAb) and 1±0.5 hours postdose (PK only), Cycle 1 Day 8 at 
168±12 hours postdose (PK, ADA, and NAb), and predose on Cycle 2 Day 1 (predose sample must be collected within 12 hours prior to infusion) (PK, ADA, and NAb). Blood 
sample for serum dostarlimab PK, ADA, and NAb will also be collected at the following time periods: Predose in Cycles 4 and 6, every 6 cycles thereafter up to 2 years, and 
the EOT Visit. In addition, blood samples for serum dostarlimab ADA and NAb will be collected at the Safety Follow-up Visit (30 days post-treatment) and at the first Follow-
up Visit (90 days post-treatment). PK, ADA, and NAb samples will be drawn at the same time points and in the same collection, except as noted. 
w. The maximum blood volume for each sample for PK, ADA, and NAb, and exploratory biomarker assessments is 0.8 mL/kg, and the maximum total blood volume allowed for 
PK, ADA, and NAb and exploratory biomarker assessments is 1.8 mL/kg per 3-week treatment cycle. Blood samples should be collected in order of priority as outlined in 
Section 8.2. 
x. 
Blood samples for plasma niraparib and M1 metabolite concentration analyses (single sample for both analytes) will be collected from participants during Cycle 1 Day 1 at 2.5 
and 7 hours after the first dose of niraparib, predose on Cycle 1 Day 8, predose on Cycle 2 Day 1, and Cycle 2 Day 1 at 5 hours after niraparib dose. Additional niraparib PK 
sampling is to be performed after a niraparib dose increase due to a birthday or after a dose modification due to a weight increase or decrease. (These additional PK samples 
will be taken on Day 1 in the first cycle after the dose change at 2.5 and 7 hours postdose, predose on Day 1 of the second cycle after the dose change, and at 5 hours after 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05  
Page 25 of 74 
the niraparib dose on Day 1 of the second cycle after the dose change). Note: Predose samples must be collected within 2 hours prior to dosing; Cycle 1 Day 1 2.5 hour 
samples must be collected at the scheduled time ±0.5 hour and other samples must be collected at the scheduled time ±2 hours. 
y. 
 
 Blood samples should be collected in order of 
priority as outlined in Section 8.2. 
 
 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 26 of 74 
Table 4: 
Tumour Assessment Flowchart 
Tumour 
Assessment 
Screening 
Period 
Treatment 
Period 
Confirmation of 
Responsea 
Post-Treatment 
Follow-up  
CT or MRI of 
chest, abdomen, 
pelvis, and any 
additional sites as 
clinically indicated 
Required 
Required, 
including sites of 
any other tumour 
lesions identified 
at baseline and of 
any additional 
sites as clinically 
indicated 
Required, 
including sites of 
any other tumour 
lesions identified 
at baseline 
If PD has been 
documented: Not 
required 
If PD has not been 
documented: 
Required, 
including sites of 
any other tumour 
lesions identified 
at baseline  
Brain scan (IV 
contrast-enhanced 
MRI [preferred] or 
IV contrast-
enhanced CT) 
Required for 
participants with 
previously 
treated brain 
metastases 
Not required 
unless clinically 
indicated  
Required if 
baseline scan was 
positive 
Not required 
unless clinically 
indicated 
Bone scan, whole 
body MRI, or PET 
scan 
Required 
Not required 
unless clinically 
indicated 
Required if 
baseline scan was 
positive for 
metastatic bone 
disease 
Not required 
unless clinically 
indicated 
Clinical assessment 
of superficial 
lesions 
Required 
Required for sites 
of tumour lesions 
identified at 
baseline and any 
additional sites as 
clinically 
indicated 
Required for sites 
of tumour lesions 
identified at 
baseline  
Required for sites 
of tumour lesions 
identified at 
baseline, unless 
PD has been 
documented 
elsewhere 
Abbreviations: CT=computed tomography; EOT=End of Treatment; MRI=magnetic resonance imaging; 
PD=progressive disease.  
Note: See Table 3 for detailed guidance on tumour assessment procedures.  
a. 
Participants who have a PR or CR while on treatment and discontinue treatment prior to the next disease assessment must 
have all appropriate follow-up disease assessments to confirm the observed response no sooner than 4 weeks (28 days) 
after the first observation 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 27 of 74 
2. 
INTRODUCTION 
An introduction to the overall study is provided in the master protocol. The objective of the 
Part 2 Safety Run-in Cohort is to evaluate the safety, tolerability and preliminary efficacy of the 
 
The objective of the Expansion Cohort of participants with osteosarcoma (the “OS Cohort”) is to 
assess the antitumour activity of the combination of niraparib and dostarlimab, assessed 
primarily by the progression-free survival rate at 6 months (PFS6) using Response Evaluation 
Criteria in Solid Tumours (RECIST) v1.1 criteria in paediatric participants. 
2.1. 
Background 
2.1.1. 
Background of Niraparib 
Overall clinical experience with niraparib is summarised in the master protocol. 
2.1.2. 
Background of Dostarlimab 
Overall clinical experience with dostarlimab is summarised in the master protocol. 
2.1.3. 
Rationale for Synergy Between PARP Inhibitors and Immune Checkpoint 
Inhibitors 
The rationale for synergy between poly (adenosine diphosphate-ribose) polymerase (PARP) 
inhibitors and immune checkpoint inhibitors is summarised in the master protocol. 
2.2. 
Rationale for Tumour Type 
 
 
 
 
  
2.3. 
Rationale for Current Study 
The rationale for the current study is provided in the master protocol. 
2.4. 
Rationale for the Primary Endpoint 
While objective response rate (ORR) is typically chosen as a primary endpoint in single-arm 
studies, RECIST v1.1 is not a tool that can reliably and consistently be utilised for evaluation of 
drug activity in osteosarcoma as this tumour type tends to stabilise or even increase in 
radiologically assessed size because of mineralisation of the stromal tissue with tumour necrosis. 
Objective responses are rare in osteosarcoma, even with proven complete necrosis in the tumour 
after neoadjuvant chemotherapy in patients with newly diagnosed disease (Lagmay, 2016). 
Given the limitations of ORR as an endpoint in studies involving participants with osteosarcoma, 
GSK/TESARO, in consultation with subject matter experts, considered PFS6 as an appropriate 
endpoint to estimate drug activity in this study. Furthermore, the median interval from initial 
diagnosis to first recurrence is 1.6 years; the median interval from first to second recurrence is 8 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 28 of 74 
to 9 months; and the median interval between subsequent recurrences remains constant at 
approximately 6 months (Bielack, 2009), supporting the choice of PFS6 as the primary efficacy 
endpoint in this cohort. 
2.5. 
Benefit Risk Assessment 
The overall benefit risk assessment and dose justification are described in the master protocol. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 29 of 74 
3. 
STUDY OBJECTIVES AND PURPOSE 
The cohort-specific objectives for this study are defined in Table 5 as follows: 
Table 5: 
Objectives and Endpoints for Study 213406 Osteosarcoma Cohort 
Objectives 
Endpoints 
Part 2 Safety Run-in 
Primary 
Assessment of safety and tolerability of the 
 
 by assessing DLTs and Grade ≥3 
thrombocytopenia AEs in paediatric participants 
• 
Assess the incidence of DLTs in the Part 2 
Safety Run-in for the DLT-evaluable 
Population. 
• 
Assess the incidence of Grade ≥3 
thrombocytopenia AEs in the Part 2 Safety 
Run-in for the DLT-evaluable Population. 
Secondary 
Evaluation of measures of anticancer activity, 
including ORR, DOR, DCR, and PFS in 
paediatric participants 
ORR is defined as the proportion of participants 
who have a BOR of confirmed CR or PR as 
determined by the Investigator using INRC for 
participants with neuroblastoma or RECIST v1.1 
for participants with osteosarcoma 
DOR is defined as the time from first 
documentation of confirmed response (CR or PR) 
until the time of first documented PD by INRC for 
participants with neuroblastoma or RECIST v1.1 
for participants with osteosarcoma based on 
Investigator assessment or death (whichever 
occurs first). 
DCR is defined as the proportion of participants 
who have achieved a BOR of confirmed CR, 
confirmed PR, or stable disease by INRC for 
participants with neuroblastoma or RECIST v1.1 
for participants with osteosarcoma based on 
Investigator assessment. 
PFS is defined as the time from the date of the 
first dose of study treatment to the first 
documented PD, as determined by INRC for 
participants with neuroblastoma or RECIST v1.1 
for participants with osteosarcoma based on 
Investigator assessment, or death from any cause 
(whichever occurs first). 
To evaluate safety of the combination of 
 
 in paediatric participants 
Assess the incidence of TEAEs, SAEs, imAEs, 
TEAEs leading to death, and AEs leading to 
treatment discontinuation. AE evaluation period is 
while participants are on treatment or up to 90 
days after the last dose of study treatment. 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 30 of 74 
Objectives 
Endpoints 
To characterise the PK of niraparib in paediatric 
participants  
Niraparib concentrations. PK parameters of 
niraparib, if appropriate. 
Part 2 Expansion 
Primary 
Assessment of the antitumour activity of the 
combination of 
, 
assessed primarily by PFS6 (using RECIST v1.1 
criteria) in paediatric participants  
PFS6 is defined as the proportion of participants 
without PD per RECIST v1.1 criteria or death at 
6 months from the date of the first dose of study 
treatment. 
Secondary 
Evaluation of additional measures of anticancer 
activity including ORR, DOR, DCR, and PFS in 
paediatric participants 
ORR is defined as the proportion of participants 
who have a BOR of confirmed CR or PR as 
determined by the Investigator using 
RECIST v1.1. 
DOR is defined as the time from first 
documentation of confirmed response (CR or PR) 
until the time of first documented PD by RECIST 
v1.1 based on Investigator assessment or death 
(whichever occurs first). 
DCR is defined as the proportion of participants 
who have achieved a BOR of confirmed CR, 
confirmed PR, or stable disease by RECIST v1.1 
based on Investigator assessment. 
PFS is defined as the time from the date of the 
first dose of study treatment to the first 
documented PD, as determined by RECIST v1.1 
based on Investigator assessment, or death from 
any cause (whichever occurs first). 
Evaluation of the safety of the combination of 
 in 
paediatric participants 
Assess the incidence of TEAEs, SAEs, imAEs, 
TEAEs leading to death, and AEs leading to 
treatment discontinuation. AE evaluation period is 
while participants are on treatment or up to 90 
days after the last dose of study treatment. 
Characterisation of the PK of the combination of 
niraparib and dostarlimab in paediatric 
participants 
Niraparib and dostarlimab concentrations; PK 
parameters of niraparib and dostarlimab, if 
appropriate. 
Assessment of the immunogenicity of dostarlimab 
in paediatric participants 
Rate and extent of ADAs to dostarlimab. 
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 31 of 74 
Objectives 
Endpoints 
Exploratory 
Abbreviations: ADA=antidrug antibody(ies); AE=adverse event; BOR=best overall response; CR=complete 
response; 
 DCR=disease control rate, DLT=dose limiting toxicity; DOR=duration 
of response; INRC=International Neuroblastoma Response Criteria; imAE=immune-mediated adverse event; 
ORR=objective response rate; 
; PD=progressive disease; 
PD-1=programmed cell death protein 1; PFS=progression-free survival; PFS6=progression-free survival rate at 6 
months; PK=pharmacokinetic(s); PR=partial response; RECIST=Response Evaluation Criteria in Solid Tumours; 
SAE(s)=serious adverse event(s); SoA=schedule of activities; TEAE(s)=treatment-emergent adverse event(s); 
. 
CCI
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 32 of 74 
4. 
INVESTIGATIONAL PLAN 
4.1. 
Overall Study Design 
The Part 2 study design is illustrated in Figure 1.  
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 33 of 74 
Once all participants in the Safety Run-in have been observed for ≥42 days, all available data 
from the Part 2 Safety Run-in together with all data previously collected under Protocol 
Amendment 04 and earlier, will be reviewed by the study DEC and Data Review Committee 
(DRC) before additional participants on Part 2 are enrolled. 
Following the Safety Run-in, if the 
 is deemed safe, up to 
30 evaluable participants may enrol in the Part 2 Cohort Expansion for osteosarcoma, inclusive 
of any eligible participants with osteosarcoma treated in the Part 2 Safety Run-in. Enrolment into 
the Part 2 Cohort Expansion will be conducted according to a Simon’s 2-stage optimal design in 
which ≥2 of the first 10 evaluable participants must achieve PFS6 before accrual of the 
remaining 20 participants. 
 
 
 
 
 
 
 
  
 
  
General study conduct is described in the master protocol. 
 
 
 
 
  
4.1.1. 
Dose Limiting Toxicity 
The DLTs and thrombocytopenia toxicities observation period for the Safety Run-in is 42 days 
following the initiation of study treatment (i.e., approximately the first 2 treatment cycles) in 
Part 2.  
A participant will be considered unevaluable for DLT assessment if, for reasons other than DLT, 
the participant does not complete the DLT observation period or receives <80% of the intended 
CCI
CCI
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 34 of 74 
niraparib dose (e.g., missed 9 or more doses; reason for missed doses may include, but is not 
limited to, noncompliance) or <2 infusions of dostarlimab.  
A participant will be considered unevaluable for thrombocytopenia events if, for reasons other 
than thrombocytopenia, the participant does not complete the DLT observation period or 
receives <80% of the intended niraparib dose (e.g., missed 9 or more doses; reason for missed 
doses may include, but is not limited to, noncompliance) or <2 infusions of dostarlimab. 
Participants considered unevaluable may be replaced after consultation between the Sponsor and 
Investigator.  
A participant may continue on study treatment following a DLT or a thrombocytopenia event if 
the Investigator determines doing so is in the best interest of the participant, after discussion by 
the Investigator with the GSK Medical Monitor, and after appropriate recovery from the DLT by 
the participant. 
DLT is defined as any of the following occurring during the first 42 days of study treatment: 
• any treatment-related Grade 4 nonhaematologic clinical (nonlaboratory) AE 
• any treatment-related Grade 3 nonhaematologic clinical (nonlaboratory) AE not resolving 
to Grade ≤1 within 48 hours of initiating optimal medical intervention 
• any treatment-related Grade 3 or 4 nonhaematologic laboratory abnormality if any of the 
following also occur:  
− the abnormality leads to hospitalisation. 
− the abnormality persists for ≥7 days from the time of AE onset and participant is 
symptomatic from the AE and/or requires intervention. 
• any treatment-related haematologic toxicity defined as any of the following:  
− Grade 4 thrombocytopenia persists for >7 days from the time of AE onset or Grade 3 
or 4 thrombocytopenia associated with clinically significant bleeding or requiring 
platelet transfusion. 
− Grade 4 neutropenia persists for >7 days, Grade 3 or 4 neutropenia associated with 
infection, or Grade 3 or 4 febrile neutropenia persists for ≥72 hours. 
− Grade 4 anaemia or Grade 3 anaemia requiring blood transfusion. 
• any treatment-related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2 
• any treatment-related Grade ≥2 uveitis, eye pain, or blurred vision that does not resolve 
with topical therapy within 2 weeks 
• any treatment-related Grade ≥2 immune-related endocrine toxicity that requires hormone 
replacement, except Grade 2 thyroiditis or thyroid dysfunction 
• any treatment-related Grade 2 colitis or diarrhoea that persists for ≥7 days without 
resolution to Grade ≤1 despite adequate steroid therapy 
• any Grade 3 or 4 imAE that does not resolve to Grade ≤1 or baseline within 8 days despite 
adequate immune suppressive therapy 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 35 of 74 
• Grade 3 or higher infusion-related reaction 
• any grade of hemophagocytic lymphohistiocytosis 
• any grade of Posterior Reversible Encephalopathy Syndrome (PRES) 
• any treatment-related Grade 5 AE 
Thrombocytopenia events are defined as any of the following occurring during the first 42 days 
of study treatment: 
• any treatment-related toxicity defined as any of the following:  
− Grade 3 or Grade 4 thrombocytopenia  
4.2. 
Number of Participants 
Safety Run-in: approximately 8 DLT-evaluable participants in total across osteosarcoma 
(Part 2A) and neuroblastoma (Part 2B). 
Part 2 Expansion: approximately 30 participants with osteosarcoma are planned for enrolment in 
this cohort (including eligible participants with osteosarcoma from the Safety Run-in). See 
Section 9.1 for eligibility requirements for enrolment of Safety Run-in participants in the Part 2 
Cohort Expansion. 
4.3. 
Treatment Assignment 
All participants enrolled in this cohort will receive niraparib in combination with dostarlimab as 
described in Section 4.1. 
4.4. 
Dose Adjustment Criteria 
4.4.1. 
Dose Adjustment Criteria for Age and Weight  
 
4.4.2. 
Dose Adjustment for Adverse Events 
Adverse reactions should be managed with dose reduction, interruption of treatment, or dose 
discontinuation. 
All dose reductions, treatment delays (including any missed doses) and discontinuations, and the 
reason for such modifications should be recorded in the eCRF. 
It should be noted that required treatment discontinuation of either niraparib or dostarlimab will 
result in study treatment discontinuation of both treatments.  
4.4.3. 
Niraparib 
The recommended dose modifications for adverse reactions should be followed as listed in 
Table 6, Table 7, and Table 8. Following a dose reduction, participants should not subsequently 
have dose re-escalated unless a discussion with the GSK Medical Monitor has occurred. 
Following 2 dose reductions, participants will not be allowed to further dose reduce, and study 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 36 of 74 
treatment should be discontinued. In addition, study treatment should be discontinued for 
selected AEs that persist beyond 28 days, as noted in Table 7 and Table 8. 
 
Table 7: 
Niraparib Dose Modifications for Nonhaematologic Adverse Reactions 
NCI CTCAE Grade ≥3 adverse reaction 
where prophylaxis is not considered 
feasible or adverse reaction event persists 
despite treatment 
• Withhold niraparib for a maximum of 28 days or until 
resolution of adverse reaction. 
• For those adverse reactions that do not resolve within 
28 days, niraparib should be discontinued. Otherwise, 
discussion with the GSK Medical Monitor is required 
to resume niraparib. 
• Resume niraparib at a reduced dose per Table 6. 
NCI CTCAE Grade ≥2 adverse reaction of 
PRES 
• 
Discontinue study treatment for participants 
Abbreviations: CTCAE=Common Terminology Criteria for Adverse Events; NCI=National Cancer Institute; 
PRES=Posterior Reversible Encephalopathy Syndrome. 
There have been rare reports of niraparib-treated patients developing signs and symptoms that 
are consistent with PRES. PRES is a rare neurologic disorder that can present with the following 
signs and symptoms including seizures, headache, altered mental status, visual disturbance, or 
cortical blindness, with or without associated hypertension. A diagnosis of PRES requires 
confirmation by brain imaging, preferably magnetic resonance imaging. In patients developing 
PRES, treatment of specific symptoms including control of hypertension is recommended, along 
with discontinuation of niraparib. The safety of reinitiating niraparib therapy in patients 
previously experiencing PRES is not known.  
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 37 of 74 
Table 8: 
Niraparib Dose Modifications for Haematologic Adverse Reactions 
Weekly blood draws for CBC will be monitored until the adverse reaction resolves; after resuming 
niraparib, weekly blood draws for CBC will be required for an additional 4 weeks (28 days) after the 
adverse reaction has been resolved to the specified levels, after which monitoring at Week 1 of each 
cycle may resume (Table 3). 
Platelet count <100 000/µL 
First occurrence: 
• Withhold niraparib for a maximum of 28 days and monitor blood 
counts weekly until platelet counts return to ≥100 000/µL. Resume 
niraparib at the same or lower dose per Table 6. 
• For those adverse reactions that do not resolve within 28 days, study 
treatment should be discontinued. Otherwise, discussion with the 
GSK Medical Monitor is required to resume niraparib. 
• Resume niraparib at the same or reduced dose per Table 6. 
• If nadir platelet count was <75 000/µL, niraparib dose should be 
reduced per Table 6. 
Second occurrence: 
• Withhold niraparib for a maximum of 28 days and monitor blood 
counts weekly until platelet counts return to ≥100 000/µL. 
• For those adverse reactions that do not resolve within 28 days, study 
treatment should be discontinued. Otherwise, discussion with the 
GSK Medical Monitor is required to resume niraparib.  
• Resume niraparib at a reduced dose per Table 6. 
Neutrophil <1000/µL or  
Haemoglobin <8 g/dL 
• Withhold niraparib for a maximum of 28 days and monitor blood 
counts weekly until neutrophil counts return to ≥1000 µL or 
haemoglobin returns to ≥8 g/dL. 
• For those adverse reactions that do not resolve within 28 days, study 
treatment should be discontinued. Otherwise, discussion with the 
GSK Medical Monitor is required to resume niraparib. 
• Resume niraparib at a reduced dose per Table 6. 
Haematologic adverse 
reaction requiring 
transfusion 
• For participants with platelet count ≤10 000/μL, platelet transfusion 
should be considered. If there are other risk factors, such as 
co-administration of anticoagulation or antiplatelet drugs, consider 
interrupting these drugs and/or transfusion at a higher platelet count. 
• Red blood cell transfusion(s) may be given at the discretion of the 
Investigator. 
• Resume niraparib at a reduced dose per Table 6. 
MDS/AML 
Any suspected case of MDS/AML reported while a participant is 
receiving treatment or followed for post-treatment assessments must be 
referred for evaluation to a local haematologist to perform bone marrow 
aspirate and biopsy as per local standards of practice. The study site 
must receive a copy of the haematologist’s report of aspirate/biopsy 
findings, which must include a classification according to the WHO, and 
other sample testing reports related to MDS/AML. If a diagnosis of 
MDS/AML is confirmed by a haematologist, the participant must 
permanently discontinue study treatment. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 38 of 74 
For clinical situations not covered by this dose modification guidance, the Investigator must 
contact the GSK Medical Monitor. 
4.4.4. 
Dostarlimab 
Dostarlimab dose adjustment criteria are presented in the master protocol. 
4.5. 
Criteria for Study Termination  
Criteria for study termination are described in the master protocol. 
4.6. 
End of Study Definition 
End of study definition is described in the master protocol. 
4.7. 
Study Conduct 
4.7.1. 
Procedures by Visit 
Standard of care tests/procedures, including laboratory assessments, ECG, physical examination, 
vital signs, height, weight, and performance status, performed before the enrolment into the 
study can be used as part of the screening assessments as long as the tests/procedures are 
performed within the visit window indicated in Table 3. Local laboratory assessments 
(chemistry, haematology) must be performed, and results reviewed no more than 7 days prior to 
administration of the first dose of study treatment, as indicated in Table 3. Tumour assessment 
CT or MRI, and bone scan, whole body MRI, or PET scan obtained per the standard of care prior 
to the first dose of study treatment (within 28 days for CT or MRI and 84 days for bone scan, 
whole body MRI, or PET scan) do not need to be repeated and are acceptable to use as baseline 
evaluations if the conditions presented in Section 8.1.2.1 of the master protocol are met. Source 
documents must clearly identify the standard of care tests/procedures that are used for Screening, 
and the results of these tests/procedures must be entered in the eCRF. Table 3 details which 
procedures are performed at each visit. 
4.7.2. 
General Guidance for Treatment Continuity when Participants are Unable to 
Come into the Clinic 
Due to the significant challenges that currently face the healthcare system and patients due to 
Coronavirus Disease 2019 (COVID-19), as well as the potential for enduring or additional 
quarantine measures, the following guidance is being provided in this protocol. In the spirit of 
global diversity in the COVID-19 pandemic and its impact on healthcare in each individual 
country as well as the recently issued guidance by several regulatory authorities, the autonomy of 
each investigative site to assess the benefit/risk for their patients participating in clinical studies 
should be maintained. 
Prior to utilisation of any of the measures outlined in this section, discussion and approval must 
be obtained from Sponsor/contract research organisation.  
It is expected that sites participating in clinical studies will make every effort to ensure proper 
monitoring and well-being of enrolled participants by adhering to safety monitoring as outlined 
in the SoA (Table 3). The use of local laboratories and local radiology centres to reduce the need 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 39 of 74 
for a participant to come into the clinic are supported, if deemed necessary for the well-being of 
the participant. These local facilities should be added to regulatory documents, as required. 
Additionally, regulatory guidance issued in response to the COVID-19 pandemic supports the 
use of central and remote monitoring programs to maintain oversight of clinical sites. Any 
restrictions in place at the site that will impact monitoring and/or participant access to the site 
and care providers should be communicated to the Sponsor/contract research organisation.  
General rules for participants with limited possibility to travel are as follows: 
• If possible, replace in-person visits with phone contact or alternative location for 
assessment (eg, local laboratories and imaging centres). 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 40 of 74 
5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrolment criteria, also known as 
protocol waivers or exemptions, are not permitted. 
5.1. 
Participant Inclusion Criteria 
Participants will be eligible for the Safety Run-in and Osteosarcoma Expansion Cohort of Part 2 
if all of the following criteria are met: 
1. 
 
 
 
2. Participant with osteosarcoma has radiologically measurable disease at screening that can 
be tracked as RECIST v1.1 target lesion(s). 
5. Performance status must be ≥60% on the Karnofsky scale for participants >16 years of 
age and ≥60% on the Lansky scale for participants ≤16 years of age. 
Note: Neurologic deficits in participants with brain metastases must have been stable for 
at least 7 days prior to study enrolment. Participants who are unable to walk because of 
paralysis, but who are upright in a wheelchair, will be considered ambulatory for the 
purpose of assessing the performance status. 
6. Participant has adequate organ function, defined as follows: 
Note: The participant must not have received blood transfusion, growth factors, or 
platelet stimulating agents in the 14 days prior to providing a sample for haematologic 
analysis nor erythropoietin in the prior 6 weeks. 
a. absolute neutrophil count ≥1000/μL 
b. platelets ≥100 000/μL 
c. haemoglobin ≥8 g/dL or ≥5.0 mmol/L 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 41 of 74 
d.  serum creatinine≤1.5×upper limit of normal (ULN) for age or calculated creatinine 
clearance or radioisotope glomerular filtration rate ≥60 mL/min/1.73m2 
e. total bilirubin ≤1.5× ULN or direct bilirubin ≤1 × ULN 
f. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN 
unless liver metastases are present, in which case AST and ALT must be ≤5 × ULN 
g. international normalised ratio or prothrombin time (PT) ≤1.5 × ULN unless the 
participant is receiving anticoagulant therapy, as long as PT or partial thromboplastin 
time (PTT) is within therapeutic range of intended use of anticoagulants 
h. activated PTT ≤1.5 × ULN unless the participant is receiving anticoagulant therapy, 
as long as PT or PTT is within therapeutic range of intended use of anticoagulants 
7. A female participant is eligible to participate if she is not pregnant or breastfeeding, and 
at least one of the following conditions applies: 
a. Is not a woman of childbearing potential (WOCBP). 
or 
b. 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 3 of the master protocol, from the Screening Visit through at least 180 days 
after the last dose of study treatment and agrees not to donate eggs (ova, oocytes) for 
the purpose of reproduction during this period. The Investigator should evaluate the 
effectiveness of the contraceptive method in relationship to the first dose of study 
treatment. 
c. A WOCBP must have a negative highly sensitive pregnancy test (urine or serum, as 
required by local regulations) within 24 hours prior to the first dose of study treatment 
and irrespective of prior medical treatment. 
Additional requirements for pregnancy testing during and after the Treatment Period are 
in the master protocol. 
The Investigator is responsible for review of medical history, menstrual history, and 
recent sexual activity to decrease the risk for inclusion of a woman with an early 
undetected pregnancy. 
8. A male participant of reproductive potential is eligible to participate if he agrees to the 
following starting with the first dose of study treatment through at least 90 days (a 
spermatogenesis cycle) after the last dose of study treatment: 
a. refrain from donating sperm 
plus, either: 
b. be abstinent from heterosexual intercourse as their preferred and usual lifestyle 
(abstinent on a long-term and persistent basis) and agree to remain abstinent 
or 
c. must agree to use a male condom and should also be advised of the benefit for a 
female partner to use a highly effective method of contraception, as a condom may 
break or leak, when having sexual intercourse with a WOCBP who is not currently 
pregnant 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 42 of 74 
9. The Investigator, or a person designated by the Investigator, will obtain written informed 
consent from each study participant or the participant’s legally acceptable representative, 
parent(s), or legal guardian and the participant’s assent, when applicable, before any 
study-specific activity is performed. The Investigator will retain the original copy of each 
participant’s signed consent/assent document.  
10. 
 
 
 
 
 
 
 
 
 
 
5.2. 
Participant Exclusion Criteria 
Participants will not be eligible for study entry if any of the following criteria are met: 
1. Participation presents unacceptable risk to the prospective participant based on the 
Investigator’s judgement. 
2. Participant has known hypersensitivity to dostarlimab or niraparib, their components, or 
their excipients. 
3. Participant has received prior therapy with an anti-PD-1, anti-programmed cell death-
ligand 1, anti-programmed cell death-ligand 2, anticytotoxic T-lymphocyte-associated 
antigen-4 antibody (including ipilimumab), or any other antibody or drug specifically 
targeting T-cell co-stimulation or checkpoint pathways (with the exception of participants 
rolling over from Part 1 of the study: these participants are allowed to have received 
dostarlimab). 
4. Participant has had prior treatment with a known PARP inhibitor (except for participants 
rolling over from Part 1 of the study: these participants are allowed to have received 
niraparib). 
5. Participant has a known history of myelodysplastic syndrome or acute myeloid 
leukaemia. 
6. Participant has active autoimmune disease that has required systemic treatment in the past 
2 years (i.e., with use of disease-modifying antirheumatic drugs, corticosteroids, or 
immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic 
corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not 
considered a form of systemic treatment. 
7. Participant has known active central nervous system metastases, carcinomatous 
meningitis, or both. Note: Participants with previously treated brain metastases may 
participate provided they are clinically stable and have no evidence of new, enlarging, or 
progressing brain metastases (using the identical imaging modality for each assessment, 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 43 of 74 
either MRI or CT scan) for at least 4 weeks (28 days) prior to the first dose of study 
treatment. In addition, the participant must not have been using steroids for at least 7 days 
prior to the first dose of study treatment. Carcinomatous meningitis precludes a 
participant from study participation regardless of clinical stability. 
8. Participant had a known additional (second primary) malignancy that progressed or 
required active treatment within the last 2 years. 
9. Participant is considered a poor medical risk due to a serious, uncontrolled medical 
disorder, nonmalignant systemic disease, or active infection that requires systemic 
therapy. Specific examples include, but are not limited to, history of (noninfectious) 
pneumonitis that required steroids or current pneumonitis, uncontrolled ventricular 
arrhythmia, uncontrolled major seizure disorder, unstable spinal cord compression, 
superior vena cava syndrome, or any psychiatric or substance abuse disorders that would 
interfere with cooperation with the requirements of the study (including obtaining 
assent/consent). 
10. Participant has a condition (such as transfusion-dependent anaemia or 
thrombocytopenia), requirement for therapy, or laboratory abnormality that might 
confound the study results or interfere with the participant’s participation for the full 
duration of the study treatment. 
11. Participant is pregnant, breastfeeding, or expecting to conceive within the projected 
duration of the study, starting with the Screening Visit through 180 days after the last 
dose of study treatment. 
No data are available regarding the presence of dostarlimab or niraparib or its metabolites 
in human milk, or on its effects on the breastfed infant or milk production. Because of the 
potential for serious adverse reactions in breastfed infants from dostarlimab and/or 
niraparib, female participants should not breastfeed during treatment with dostarlimab 
and/or niraparib and for at least 4 months after the last dose of dostarlimab or at least 30 
days after the last dose of niraparib, whichever is longer. 
12. Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy 
or any other form of immunosuppressive therapy within 7 days prior to the first dose of 
study treatment. 
13. Participant has a known history of HIV (type 1 or 2 antibodies). 
14. Participant has documented presence of HbsAg and/or HBcAb at Screening or within 
3 months prior to first dose of study intervention. Participants with a negative HbsAg and 
positive HbcAb result are eligible only if HBV DNA is negative (Appendix 12 of the 
master protocol). 
15. Participant must not have a gastrointestinal condition, such as bowel obstruction, that can 
impact absorption of oral medications and is identified by clinical symptoms or CT scan, 
etc. 
16. Participant has had any known Grade 3 or 4 anaemia, neutropenia, and/or 
thrombocytopenia that was related to the most recent prior anticancer treatment and that 
persisted >4 weeks (28 days).  

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 44 of 74 
17. Participant has not recovered (i.e., to Grade ≤1 or to baseline) from prior systemic 
therapy-induced adverse events (AEs). Note: Participants with alopecia, hearing 
impairment, Grade ≤2 neuropathy, Grade ≤2 fatigue, Grade ≤2 anaemia, and/or Grade ≤2 
neutropenia are an exception to this criterion and may qualify for participation in the 
study. 
18. Participant had toxicity related to prior immunotherapy that led to treatment 
discontinuation. 
19. Participant had treatment with systemic anticancer therapy (investigational agent or 
device, or approved chemotherapy, targeted therapy, immunotherapy, or other systemic 
therapy) within the 3 weeks or 5 half-lives, whichever is shorter prior to the first dose of 
study treatment, radiation therapy encompassing >20% of the bone marrow within 
2 weeks prior to the first dose of study treatment, or any radiation therapy within 1 week 
prior to the first dose of study treatment. 
20. Participant has not recovered adequately from AEs or complications from any major 
surgery prior to starting study treatment. 
21. Participant has received a live vaccine within 30 days of planned start of study treatment. 
22. Participant has clinically significant cardiovascular disease (eg, significant cardiac 
conduction abnormalities, uncontrolled hypertension, cardiac arrhythmia or unstable 
angina, New York Heart Association Grade 2 or greater congestive heart failure, serious 
cardiac arrhythmia requiring medication, and history of cerebrovascular accident) within 
6 months of enrolment. 
23. Participant has heart rate-corrected QT interval prolongation at Screening >450 msec or 
>480 msec for participants with bundle branch block. 
Notes: 
• The QTc is the QT interval corrected for heart rate according to Bazett’s formula 
(QTcB), Fridericia’s formula (QTcF), and/or another method, machine read or 
manually over read. 
• The specific formula that will be used to determine eligibility and discontinuation for 
an individual participant must be determined prior to initiation of the study and used 
consistently for eligibility and study assessments.  
24. Participant has received solid organ transplant.  
25. Participant has a documented presence of HCV antibody at Screening or within 3 months 
prior to first dose of study intervention. NOTE: Participants with a positive HCV 
antibody test result due to prior resolved disease can be enrolled, only if a confirmatory 
HCV RNA test is negative and the participant otherwise meets entry criteria. 
26. Participant has a documented presence of HCV RNA at Screening or within 3 months 
prior to first dose of study intervention. NOTE: The HCV RNA test is optional and 
participants with negative HCV antibody test are not required to undergo HCV RNA 
testing as well. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 45 of 74 
5.3. 
Lifestyle Considerations 
Cases of photosensitivity have been reported for patients on niraparib treatment. Participants 
must be informed on measures to decrease exposure to ultraviolet light, such as minimising time 
in direct sunlight unless wearing hats and long-sleeves and application of sun protection creams. 
5.4. 
Screen Failures 
The definition of a screen failure is provided in the master protocol. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 46 of 74 
6. 
STUDY TREATMENT(S) AND CONCOMITANT THERAPY 
6.1. 
Study Treatment(s) Administered 
Niraparib will be dispensed to participants on Day 1 of every 21-day treatment cycle. 
The niraparib dosing regimens under Protocol Amendment 05 are shown in master protocol.  
 
 
Details about the investigational products are provided in Table 9. 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 47 of 74 
Table 9: 
Investigational Products 
 
Investigational Product 
Intervention name Niraparib 
Niraparib 
Dostarlimab 
Type 
Drug 
Drug 
Biologic 
Dosage form 
Unit dose 
Route of 
administration 
Use 
IMP 
IMP 
IMP 
Authorised AxMP/ 
Unauthorised 
AxMP 
Not applicable 
Not applicable 
Not applicable 
Sourcing 
Provided centrally by the 
Sponsor 
Provided centrally by the 
Sponsor 
Provided centrally by the 
Sponsor 
Physical 
description 
(Packaging and 
Labelling; see 
Section 6.2.1) 
Dose level(s) 
See master protocol 
See master protocol 
See master protocol 
Manufacturer 
WuXi STA (WuXi), 
China (DS, DP) 
Dishman, India (DS) 
Corden, Colorado, US 
(DS) 
Mayne Pharma, Raleigh, 
North Carolina, US (DP) 
Siegfried, Switzerland 
(DS) 
WuXi STA (WuXi), 
China (DS, DP) 
Corden, Colorado, US 
(DS) 
Dishman, India (DS) 
Siegfried, Switzerland 
(DS) 
WuXi Biologics (WuXi), 
Wuxi, China (DS) 
Ajinomoto Althea (Aji), 
San Diego, California, US 
(DP) 
Abbreviations: AxMP = auxiliary medicinal product; DP=drug product; DS=drug substance; IMP = investigation 
medicinal product; IV=intravenous; Non-IMP = non-investigational medicinal product; 
 
; US=United States. 
Further details on the study interventions are provided in the master protocol and respective IBs. 
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 48 of 74 
6.2. 
Preparation/Handling/Storage/Accountability 
6.2.1. 
Study Treatment Packaging and Labelling 
Overall study treatment packaging and labelling are described in the master protocol. 
6.2.2. 
Study Treatment Storage 
Study treatment storage is described in the master protocol. 
6.2.3. 
Administration 
Details on the administration of the study treatments can be found in the Pharmacy Manual. A 
summary is provided in the master protocol. 
6.2.4. 
Study Treatment Accountability 
Study treatment accountability is described in the master protocol. 
6.2.5. 
Study Treatment Handling and Disposal 
Study treatment handling and disposal are described in the master protocol. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
This is a non-randomised, open-label study. 
6.4. 
Study Treatment Compliance 
Overall study treatment compliance information is presented in the master protocol. Study 
treatment (dostarlimab and niraparib during dostarlimab infusion visits) will be administered by 
investigational site personnel at investigational sites. 
6.5. 
Dose Modification 
Dose reductions for dostarlimab are not permitted while participant is being treated on study. 
Dosing may be held in the event of an AE which may be deemed related to treatment. If 2 or 
more consecutive dostarlimab doses are held, Investigator must notify the GSK Medical Monitor 
for approval to continue treatment of the participant on study.  
Refer to Section 4.4 for full dose modification guidance for niraparib and Section 4.7 in the 
master protocol for full dose modification guidance for dostarlimab. 
6.6. 
Treatment of Overdose 
This information is described in the master protocol.  
6.7. 
Concomitant Therapy 
Details on the definition and recording of concomitant medications are provided in the master 
protocol. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 49 of 74 
6.7.1. 
Rescue Medications 
Participants should receive appropriate supportive care measures as deemed necessary by the 
treating Investigator, including but not limited to the items outlined in Section 6.8.1 of the master 
protocol.  
6.7.2. 
Prohibited Medications 
Known prior medications that exclude a participant from participating in this cohort are 
described in the exclusion criteria (see Section 5.2). 
Medications prohibited in the overall study are provided in the master protocol. 
6.7.3. 
Other Study Restrictions 
Other study restrictions are provided in the master protocol. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 50 of 74 
7. 
DISCONTINUATION OF STUDY TREATMENT AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of Study Treatment 
Guidance on discontinuation of study treatment is described in the master protocol. 
7.1.1. 
Liver Chemistry Stopping Criteria 
Specific guidance on liver chemistry stopping criteria is described in the master protocol in 
Section 7.1.1 and Appendix 8. Guidance on drug restart or rechallenge following liver safety 
events, if applicable, is included in Appendix 9 of the master protocol.  
7.1.2. 
QTc Stopping Criteria 
Guidance on QTc stopping criteria is described in the master protocol. 
7.2. 
Withdrawal of Consent 
Procedures to be followed in cases of consent withdrawal are presented in the master protocol. 
7.3. 
Participant Discontinuation/Withdrawal from the Study 
Examples of reasons for discontinuing study treatment or study are applicable across cohorts and 
are presented in the master protocol. 
Guidance on discontinuation of participants from the study, including required actions for 
participants lost to follow-up, is provided in the master protocol. 
7.4. 
Lost to Follow-Up 
Guidance on required actions for participants lost to follow-up is provided in the master protocol. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 51 of 74 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
8.1. 
Assessment of Efficacy 
The timing of radiologic evaluations and details regarding the evaluation of tumour response for 
both the Part 2 Safety Run-in and the Part 2 Osteosarcoma Expansion Cohort are provided in 
Table 3 and in the master protocol. Participant scan data are not routinely collected in this study; 
however, such data may be requested under special circumstances such as during investigation of 
a significant safety event. 
8.1.1. 
Primary Efficacy Endpoint for the Osteosarcoma Cohort Expansion 
The primary efficacy endpoint for this cohort will be PFS6, defined as the proportion of 
participant without PD per RECIST v1.1 criteria or death at 6 months from the date of the first 
dose of study treatment. 
8.1.2. 
Secondary Efficacy Endpoints for the Osteosarcoma Cohort Expansion 
The secondary endpoints for this cohort will be ORR, DOR, DCR, and PFS based on 
Investigator assessment using RECIST v1.1. 
8.1.2.1. 
Objective Response Rate 
ORR is defined as the proportion of participants who have a best overall response (BOR) of 
confirmed complete response (CR) or partial response (PR) as determined by the Investigator 
using RECIST v1.1. 
8.1.2.2. 
Duration of Response 
DOR is defined as the time from first documentation of confirmed response (CR or PR) until the 
time of first documented PD by RECIST v1.1 based on Investigator assessment or death 
(whichever occurs first). This will only be calculated for participants who have a BOR of 
confirmed CR or PR. Participants who do not experience PD or who die after they have had a 
response are censored at the date of their last tumour assessment. 
8.1.2.3. 
Disease Control Rate 
DCR is defined as the proportion of participants who have achieved a BOR of confirmed CR, 
confirmed PR, or stable disease by RECIST v1.1 based on Investigator assessment. 
8.1.2.4. 
Progression-free Survival 
PFS is defined as the time from the date of the first dose of study treatment to the first 
documented PD, as determined by RECIST v1.1 based on Investigator assessment, or death from 
any cause (whichever occurs first). Participants without an event will be censored at the date of 
the last tumour assessment. Participants without postbaseline assessments will be censored at the 
date of the first dose. 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 52 of 74 
8.2. 
Assessment of Safety 
Planned time points for all safety assessments are provided in Table 3. 
At some timepoints, the protocol may specify that blood samples for clinical care (i.e., clinical 
chemistry, haematology, pregnancy) and for study-related research (PK, exploratory biomarkers) 
be obtained during a single study visit. In the event of concern for excessive blood volume 
withdrawal sample collection should be prioritised as follows: 
1. clinical care 
2. niraparib PK 
3. dostarlimab PK, ADA, and NAb 
4. 
 
8.2.1. 
Safety Parameters 
Safety parameters for this study are described in the master protocol. 
8.3. 
Adverse Events and Serious Adverse Events 
Definitions and guidance on AEs and SAEs are provided in the master protocol. 
8.4. 
Pharmacokinetics, Immunogenicity, and Biomarkers  
Blood samples to assess niraparib PK, dostarlimab PK, and dostarlimab antidrug antibodies 
(ADAs) and NAb will be collected from all participants pre- and postdose at the time points 
specified in Table 3. 
 
 
 
 
  
Sample collection should be prioritised as outlined in Section 8.2. 
Additional details concerning PK and immunogenicity sample collection are provided in the 
master protocol. 
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 53 of 74 
8.6. 
Health Economics 
Health Economics parameters are not evaluated in this study.  
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 54 of 74 
9. 
STATISTICAL CONSIDERATIONS 
An overall description of the statistics for this study is provided in the master protocol. 
Additional details are provided in the Statistical Analysis Plan. 
9.1. 
Sample Size Determination 
Part 2 Safety Run-In  
The statistical gating to initiate the Part 2 Cohort Expansion will be based on minimum of 8 
DLT-evaluable participants for DLTs across osteosarcoma and neuroblastoma. When 2 or less 
DLTs and 2 or less Grade ≥3 thrombocytopenia AEs are observed, the study will continue to 
Part 2 Cohort Expansion. When 3 or more DLTs are observed, the study may not continue to 
Part 2 Cohort Expansion. When 2 or less DLTs and 3 out of 8 Grade ≥3 thrombocytopenia AEs 
are observed, the study may be paused for data review. If there is a differential in the DLT-
evaluable number of participants to 8 for either endpoint, other criteria may apply and will be 
specified in the SAP. This will be the primary guideline for the dose recommendations; the 
totality of data will be taken into account. The probability of initiating Part 2 Cohort Expansion 
and the probability of pausing for data review are presented in the table below for 8 DLT-
evaluable participants, assuming a weak correlation of 0.15 between the 2 endpoints. 
True DLT 
Rate 
True Grade ≥3 
Thrombocytopenia 
Rate 
Probability of Initiating Part 2 Cohort 
Expansion (2 or Less DLTs and 2 or 
Less Grade ≥3 Thrombocytopenia 
Events Observed Out of 8 DLT-
evaluable Participants) 
Probability of Pausing for Data 
Review (3 Grade ≥3 
Thrombocytopenia Events and 
2 or Less DLTs Observed Out 
of 8 DLT-evaluable 
Participants) 
0.25 
0.25 
49% 
13% 
0.30 
0.25 
40% 
10% 
0.30 
0.30 
32% 
13% 
0.35 
0.35 
21% 
11% 
0.45 
0.45 
6% 
6% 
 
Part 2 Cohort Expansion 
The sample size for this cohort is based on a Simon’s 2-stage optimal design, with a 1-sided 
alpha of 0.05 and a minimum power of 80%. The null hypothesis is ≤10% PFS6, and the 
alternative hypothesis is ≥30% PFS6. A futility analysis will be performed after the initial 
assessment of response for 10 evaluable participants in the cohort. If, among the 10 mITT 
participants in the cohort, at least 2 participants remain progression-free after 6 months, an 
additional 19 mITT participants will be enrolled. If 6 or more participants out of the 
29 participants enrolled remain progression-free after 6 months, the null hypothesis will be 
rejected. The required sample size of 29 is based on the modified Intent-to-Treat (mITT) 
Population. The total sample size to be enrolled is planned at approximately 30 in case of the 
potential lack of sufficient participants in the mITT Population. For consideration of futility, 
those Part 1 participants who satisfy the inclusion and exclusion criteria of Part 2, satisfy the 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 55 of 74 
mITT Population definition, and are treated at the dose used in Part 2 Cohort Expansion will be 
included in the Part 2 efficacy analysis and will be counted in the required Part 2 Cohort 
Expansion sample size. Under Protocol Amendment 05, osteosarcoma Safety Run-in participants 
who satisfy the mITT Population definition and are treated at the modified dose used in the 
Part 2 Cohort Expansion will also be included in the Part 2 Cohort Expansion efficacy analysis 
and will be counted in the required Part 2 Cohort Expansion sample size. The software for the 
sample size calculation is PASS 2019 (NCSS). 
9.2. 
Analysis Populations 
For the purposes of analysis, the following analysis sets are defined as follows in Table 10. 
Table 10: 
Analysis Sets 
Participant Analysis Set 
Description 
DLT-evaluable 
The DLT-evaluable Population consists of participants in 
Part 2 Safety Run-in who complete the DLT observation 
period through at least 2 cycles of study treatment 
(including ≥80% of the intended niraparib dose and ≥2 
infusions of dostarlimab) or experience a DLT for DLT 
endpoint (or Grade ≥3 thrombocytopenia AEs for the 
thrombocytopenia event endpoint). 
Safety 
The Safety Population is defined as all participants who 
receive at least 1 dose of either niraparib or dostarlimab. 
Intent-to-Treat (ITT) 
The ITT Population includes all participants who receive 
any study medication and have measurable baseline tumour 
assessment. 
Modified Intent-to-Treat (mITT) 
The mITT Population includes all participants who receive 
any study medication, have measurable baseline tumour 
assessment, and have at least 1 postbaseline tumour 
assessment. 
Per-Protocol  
The Per-Protocol Population includes all participants in the 
mITT Population who do not have protocol violations 
during the study that may significantly impact the 
interpretation of efficacy results. 
Pharmacokinetic (PK) 
The PK Population includes all participants who receive at 
least one dose of study treatment and have at least one PK 
sample. PK Populations are defined separately for each 
agent. 
Immunogenicity (ADA) Population  
The ADA Population includes all participants who receive 
at least 1 dose of dostarlimab and who have at least 1 ADA 
sample with a result.  

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 56 of 74 
9.3. 
Statistical Analyses 
9.3.1. 
General Considerations 
All analyses will include summary statistics, including number of participants and percentage for 
categorical variables and number of participants, mean, standard deviation, median, minimum, 
and maximum for continuous variables. Two-sided exact 95% CIs based on the Clopper-Pearson 
method will be provided where appropriate (Clopper, 1934). Time-to-event analyses will be 
performed using Kaplan-Meier methods. 
The primary analysis set for the efficacy endpoints will be the mITT Population. 
9.3.2. 
Primary Endpoints 
The primary endpoints for the Safety Run-in and Part 2 Osteosarcoma Cohort Expansion are 
defined in Section 3; the primary endpoint for the Part 2 Osteosarcoma Cohort Expansion is also 
defined in Section 8.1.1. 
For the Safety Run-in, the incidence of DLTs and incidence of Grade ≥3 thrombocytopenia AEs 
will be summarised in the DLT-evaluable Population. 
For the Part 2 Osteosarcoma Cohort Expansion, PFS6 and its 2-sided 95% CI will be estimated 
using the Clopper-Pearson method. 
9.3.3. 
Secondary Endpoints 
The secondary endpoints for the Safety Run-in and Part 2 Osteosarcoma Cohort Expansion are 
outlined in Section 3 and, for Part 2 Osteosarcoma Cohort Expansion, also in Section 8.1.2. 
The number and proportion of participants with an objective response will be tabulated. ORR 
and DCR will be calculated, along with their estimated 2-sided 95% CI. Among the participants 
with a confirmed response, a time-to-event analysis of DOR will be performed using Kaplan-
Meier methods, including quartile estimates and 2-sided 95% CI. PFS and its 2-sided 95% CI 
will be estimated using the Kaplan-Meier method. 
9.3.3.1. 
Safety Analyses 
Safety analyses of this study are described in the master protocol. 
9.3.3.2. 
PK Analysis 
PK analyses in this study are described in the master protocol. 
9.3.3.4. 
Immunogenicity Analysis 
Immunogenicity analysis in this study is described in the master protocol. 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 57 of 74 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 58 of 74 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
The regulatory and ethical considerations of the study are outlined in Appendix 1 of the master 
protocol.  

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 59 of 74 
11. 
APPENDICES   
The following appendices in the master protocol should be referenced for the necessary guidance 
for this cohort. 
Appendix 1 
Regulatory, Ethical, and Study Considerations 
Appendix 2 
Adverse Events and Serious Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-Up, and Reporting 
Appendix 3 
Contraception Guidelines 
Appendix 4 
Guidelines for Assessment of Disease, Disease Progression and Response Criteria – 
Adapted from RECIST 1.1 
Appendix 6 
List of Abbreviations and Definitions of Terms 
Appendix 8 
Liver Safety: Required Actions and Follow-up Assessments 
Appendix 9 
Liver Safety Drug Restart or Rechallenge Guidelines 
Appendix 12 
Consideration for Participants with Past HBV Infection 
 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 60 of 74 
APPENDIX 1. PROTOCOL AMENDMENT HISTORY 
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the Table of Contents. 
Amendment 01 (16 October 2020) 
Overall Rationale for Amendment 01 
Amendment 01 revised the protocol requirement for tumour assessments to be aligned with 
current standard of care and provides other clarifications and editorial changes catalogued since 
the issuance of the prior version of the protocol. Additionally, minor changes to the time allowed 
for safety reporting to ensure consistency with GSK standard practices.  
Summary of Changes for the Amendment 
Table 2 
Summary of Changes for Amendment 01 
Section(s) Affected 
Description of Change 
Brief Rationale 
Headers, cover page, and 
Protocol Amendment Summary 
of Changes 
Headers and cover page were 
updated with new version 
number; headers were updated 
with new document number; 
Protocol Amendment Summary 
of Changes section was updated 
to include rationale for this 
version. 
Editorial changes to align with 
the Sponsor’s standard protocol 
template and ways of working 
and inclusion of specific 
language noted during Health 
Authority review 
Section 1.3 Schedule of 
Activities 
Revision to footnote for vital 
signs assessment to include 
guidance for blood pressure 
monitoring  
 
Deletion of minimum body 
weight criteria for PK 
parameters 
 
Revision of language for 
collection of information for 
SAEs and AEs 
Alignment with niraparib safety 
monitoring in accordance with 
Investigator’s Brochure, and 
Package Insert/Summary of 
Product Characteristics  
 
Deletion of information 
inadvertently propagated 
throughout protocol in error 
 
Removal of discrepant 
information and improved 
clarity 
Section 1.3 Schedule of 
Activities 
 
Table 4 Tumour Assessment 
Flowchart 
Revision of preferred imaging 
types and schedule for scans; 
additionally, Schedule of 
Activities revised to separate 
imaging assessments according 
to different timings for standard 
of care and type of assessments 
Allowable imaging types and 
schedule revised to align with 
current standard of care 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 61 of 74 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 4.7.1 Procedures by 
Visit 
Revision of preferred imaging 
types and schedule for scans 
Allowable imaging types and 
schedule revised to align with 
current standard of care 
Section 4.7.2 General Guidance 
for Treatment Continuity when 
Participants are Unable to Come 
into the Clinic 
New section added 
Additional guidance to sites 
included in light of COVID-19  
Synopsis 
Section 5.1 Inclusion Criteria 
Minimum threshold of 
performance status reduced to 
60% in Inclusion #4 
Criteria for adequate CBC 
collection result revised to 1 
week in Inclusion #5 
Minimum threshold of absolute 
neutrophil count reduced to 
≥1,000/μL in Inclusion #5 
Revision to align with standard 
of care 
Revision to align with standard 
of care 
Revised safety monitoring 
guidance 
Section 9.2 Analysis 
Populations 
Immunogenicity populations 
included 
Provided for clarity as to 
analysis populations intended to 
be studied 
Abbreviations: AE=adverse event; CBC=complete blood count; COVID-19=Coronavirus Disease 2019; 
PK=pharmacokinetic; SAE=serious adverse event. 
 
Amendment 02 (23 November 2020) 
Overall Rationale for the Amendment 
Amendment 02 revises the protocol to include specific safety language noted during Health 
Authority review as detailed in Table 2. 
Summary of Changes for the Amendment 
Table 2: 
Summary of Changes for Amendment 02 
Section(s) Affected 
Description of Change 
Brief Rationale 
Headers, cover page, Protocol 
Amendment Summary of 
Changes, Appendix 1. Protocol 
Amendment History (new), and 
throughout 
Headers and cover page were 
updated with new version 
number; headers were updated 
with new document number; 
Protocol Amendment Summary 
of Changes section was updated 
to include rationale for this 
amendment and administrative 
information for prior 
amendment was moved to new 
Appendix 1. Protocol 
Editorial changes to align with 
the Sponsor’s standard protocol 
template and ways of working, 
for conformity, clarity, flow, 
and typographical error 
correction, and for inclusion of 
specific language noted during 
Health Authority review 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 62 of 74 
Section(s) Affected 
Description of Change 
Brief Rationale 
Amendment History. Editorial 
changes made throughout. 
Section 1.1. Synopsis (Main 
Criteria for Inclusion) 
Section 5.1. Participant 
Inclusion Criteria 
Clarified that participants must 
not be eligible for local curative 
treatment (criterion 1) 
Participants who are eligible for 
local curative treatment are not 
permitted in the study 
Section 1.1. Synopsis (Main 
Criteria for Exclusion)  
Section 5.2. Participant 
Exclusion Criteria 
Added language for exclusion in 
cases of pregnant or 
breastfeeding participants 
(criterion 11) 
Modified that a participant 
should not have received a live 
vaccine within 30 days of 
starting study treatment 
(criterion 20) (changed from 14 
days) 
Clarified that participants with 
QT interval prolongation >480 
ms at screening are not eligible 
and no waivers are allowed 
(criterion 22) 
Participants who are pregnant or 
breastfeeding are excluded from 
the study 
Participants must not receive 
live vaccines within 30 days of 
starting study treatment 
Participants with QT interval 
prolongation >480 ms at 
screening are not eligible for the 
study 
Section 1.3. Schedule of 
Activities/Table 3: Schedule of 
Activities (footnote c) 
Clarified that, during the 
long-term Follow-Up 
Assessment Period, follow-up 
might be conducted via a clinic 
visit or telephone contact 
To accurately reflect study 
conduct 
Section 1.3. Schedule of 
Activities/Table 3: Schedule of 
Activities, Table 4: Tumour 
Assessment Flow Chart 
Updated Table 3 and Table 4 to 
reflect editorial updates made in 
the master protocol 
To align with the master 
protocol 
Section 5.3. Lifestyle 
Considerations 
Added that participants should 
avoid exposure to ultraviolet 
light and take precautions when 
exposed to direct sunlight 
Added due to the fact that 
photosensitivity has been 
reported for patients receiving 
niraparib 
 
Amendment 03 (20 Jul 2022) 
Overall Rationale for Amendment 03: 
• To update secondary objective and/or endpoint for PK and immunogenicity. 
• To update inclusion and exclusion criteria. 
• To increase clarity and/or remove discrepancies. 
All changes are listed in table below. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 63 of 74 
Table 2: 
Summary of Changes for Amendment 03 
Section(s) Affected 
Description of Change 
Brief Rationale 
Headers, title page, Protocol 
Amendment Summary of 
Changes, Appendix 1. Protocol 
Amendment History, and 
throughout 
Headers and cover page were 
updated with new version 
number; headers were updated 
with new document number; 
Protocol Amendment Summary 
of Changes section was updated 
to include rationale for this 
amendment and administrative 
information for prior 
amendment was moved to 
Appendix 1. Protocol 
Amendment History. Editorial 
changes made throughout. 
Editorial changes to align with 
the Sponsor’s standard protocol 
template and ways of working 
Title page 
Updated compound number 
“GSK4057190 to 
GSK4057190A” 
To present current correct 
compound number 
Section 1.1 Synopsis (Secondary 
objectives) 
 
Section 3 Study Objectives and 
Endpoints 
Added new secondary objective; 
to assess the immunogenicity of 
dostarlimab in paediatric 
participants 
To correct lack of secondary 
objective given immunogenicity 
analyses are described in the 
protocol and an immunogenicity 
population is defined in Section 
9 Statistical Considerations 
Section 1.1 Synopsis 
(Methodology) Data Review 
Committee 
Updated information for 
establishment and composition 
of an independent data oversight 
committee 
To clarify that a committee that 
is independent of all aspects of 
the study and that is dedicated to 
oversight of safety and efficacy 
data from participants in Part 2 
will be established. To clarify 
that details of committee 
composition and function will 
be described in a formal charter. 
To indicate that the RP2D 
 
 as 
determined in Part 1A of the 
study is the dose that is to be 
advanced and evaluated in Part 
2 of the study. 
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 64 of 74 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 1.1. Synopsis 
(Diagnosis and Main Criteria for 
Inclusion: criterion 6) 
Section 5.1. Participant 
Inclusion Criteria (criterion 6) 
Updated note describing timing 
for collection of blood sample 
for complete blood count 
To better describe a correct and 
more reasonable washout period 
for support agents (transfusion, 
colony-stimulating factors, 
erythropoietin) received prior to 
collection of blood for complete 
blood count during screening.  
Section 1.1. Synopsis 
(Diagnosis and Main Criteria for 
Exclusion: criterion 10) 
Section 5.2. Participant 
Exclusion Criteria (criterion 10) 
Removed bullets on blood 
transfusion and growth factors 
in exclusion criterion 10 
Permitted window prior to first 
dose of study treatment has been 
updated in inclusion criterion 5. 
The permitted windows in 
exclusion criterion 10 no longer 
are applicable and, therefore, 
were removed. 
Section 1.1. Synopsis 
(Diagnosis and Main Criteria for 
Exclusion: criterion 15) 
Section 5.2. Participant 
Exclusion Criteria (criterion 15) 
Deleted original exclusion 
criterion 15 (this text was 
combined with text for 
exclusion criterion 19 as 
described below) and replaced 
with “Participant must not have 
a gastrointestinal condition, such 
as bowel obstruction, that can 
impact absorption of oral 
medications and is identified by 
clinical symptoms or CT scan, 
etc” 
To update exclusion criteria to 
include additional criterion to 
support participant safety. 
Section 1.1. Synopsis 
(Diagnosis and Main Criteria for 
Exclusion: criterion 16) 
Section 5.2. Participant 
Exclusion Criteria (criterion 16) 
Updated exclusion criteria 16 to 
clarify guidance on hematologic 
side effects from prior 
anticancer therapy. 
To clarify information on 
excluded cytopenia occurrence 
and duration 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 65 of 74 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 1.1. Synopsis (Main 
Criteria for Exclusion: criterion 
18)  
Section 5.2: Participant 
Exclusion Criteria (criterion 18) 
Added new exclusion criteria 
“Toxicity related to prior 
immunotherapy that led to study 
treatment discontinuation.” 
To include guidance for 
enrolment of patients who had 
previously experienced toxicity 
in response to immunotherapy 
and to align eligibility 
requirements with those of 
dostarlimab protocols in general. 
Section 1.1. Synopsis 
(Diagnosis and Main Criteria for 
Exclusion: criterion 19) 
Section 5.2. Participant 
Exclusion Criteria (criterion 15) 
Section 5.2. Participant 
Exclusion Criteria (criterion 19) 
• 
Deleted original exclusion 
criterion 15. 
• 
Updated exclusion 
criterion 19 to clarify 
permitted window relative 
to first dose of study 
treatment for prior 
systemic anticancer 
therapy. Combined text 
from exclusion criterion 
15 with text in exclusion 
criterion 19. 
To update permitted window for 
receipt of prior anticancer 
therapy from “within 3 weeks” 
prior to first dose of study 
treatment to “within 3 weeks or 
5 half-lives, whichever is 
shorter” - a change which was 
made in response to an 
investigator’s suggestion and 
which reflects half-life data for 
most common standard of care 
therapies enrolled patients with 
the specified tumour types. 
In addition, to make the 
excluded window consistent for 
investigational agents or devices 
and for approved systemic 
therapies of all types.  
Section 1.1. Synopsis 
(Diagnosis and Main Criteria for 
Exclusion: criterion 23) 
Section 5.2. Participant 
Exclusion Criteria (criterion 23) 
Updated exclusion criterion 23 
with corrected QTc values and 
added instructional text. 
To align excluded QTc values 
with values appropriate for 
participants to be treated with 
dostarlimab. 
Section 1.1. Synopsis 
(Diagnosis and Main Criteria for 
Exclusion: criterion 24) 
Section 5.2. Participant 
Exclusion Criteria (criterion 24) 
Added exclusion criteria 24 to 
clarify that solid organ 
transplant is not permitted. 
To prohibit enrolment of 
participants who are receiving 
immunosuppressive therapy that 
might impact effectiveness of 
dostarlimab as a PD-1 inhibitor. 
Section 1.1. Synopsis (Analysis 
Population) 
Section 9.2 Analysis Population 
Table 7 
Revised definition of PK 
population and immunogenicity 
populations 
To more accurately describe 
which participants qualified for 
inclusion in each population 
Section 1.3. Schedule of 
Activities (Table 3) 
Added “Post Treatment” to 
column header for FUP 
assessment Period 
To align column header content 
with text clarifying that Follow-
up visits were to occur every 90 
days following end of study 
treatment.  

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 66 of 74 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 1.3 Schedule of 
Activities (Table 3) 
Removed -10-day window from 
Screening period 
To correct outside limit of 
Screening activities window to -
28 days rather than -28 days +10 
additional days. 
Section 1.3. Schedule of 
Activities (Table 3 and Footnote 
j) 
Addition of pregnancy testing 
for WOCBP at End of 
Treatment and 30-day Safety 
Follow-up Visits 
To ensure pregnancy did not 
occur during the excluded 
period. 
Section 1.3. Schedule of 
Activities (Table 3 and Footnote 
l) 
Addition of 12-lead ECG testing 
added in Cycle 3 
In line with study level 
requirements 
Section 1.3 Schedule of 
Activities (Table 3 and Footnote 
q, r) 
Added text indicating that 
tumour assessments should be 
conducted every 9 weeks (every 
63 [±7] days) from the start of 
study treatment for the first 12 
months and then every 12 weeks 
(every 84 [±7] days) thereafter, 
To reduce total number of scans 
conducted throughout duration 
of participant enrolment and 
thereby reduce radiation 
exposure overall. 
Section 1.3 Schedule of 
Activities (Table 3) 
Merged cells for EOT Visit, 
Safety FUP Visit, and FUP 
Assessment Period for the rows 
for several disease assessment 
activities  
To clarify that measures of 
disease assessment are to 
continue throughout the EOT 
and follow-up periods. 
Section 1.3. Schedule of 
Activities (Table 3 Footnote b) 
Added additional details on 
safety FUP visit 
To clarify the Safety FUP visit 
window 
Section 1.3. Schedule of 
Activities (Table 3 Footnote c) 
Clarified long-term follow-up 
assessment period 90 (±14) days 
“after the last dose of study 
treatment” 
To clearly define specific 
starting point from which to 
initiate long-term follow-up 
safety assessments 
Section 1.3. Schedule of 
Activities (Table 3 Footnote i) 
Updated to replace baseline with 
“Cycle 1 Day 1” and to clarify 
guidance for Cycle 1 Day 1 
sample collection. 
To clarify that if the screening 
laboratory samples were 
collected within 7 days prior to 
Cycle 1 Day 1, then collection 
of these samples did not need to 
be repeated for Cycle 1 Day 1. 
Section 1.3 Schedule of 
Activities (Table 3 Footnote m) 
Removed the language that 
“MRI should only be used if 
clinically appropriate, when CT 
is contraindicated, and 
preferably for imaging of the 
brain” 
To remove restrictions to use of 
MRI in medically appropriate 
scanning situations  

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 67 of 74 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 1.3 Schedule of 
Activities (Table 3 Footnote v) 
Added text clarifying required 
duration of AE collection 
To clarify that collection of AEs 
is to continue throughout the 
required 30-day interval even in 
the event of initiation of 
additional anticancer treatment. 
Section 1.3 Schedule of 
Activities (Table 3 Footnote y) 
Added text clarifying collection 
interval for PK sample 
collection 
To clarify that timing of PK 
sample collection is relative to 
time of participant’s very first 
dose of niraparib. 
Section 1.3. Schedule of 
Activities (Table 3 Footnote w, 
x and z) 
Updated information for 
dostarlimab PK, ADA, 
neutralising antibodies, and 
biomarker sample collection 
To provide additional guidance 
for procedures and timing of 
dostarlimab PK, ADA, and 
biomarker sampling. 
Section 2.5 Benefits and Risks 
Assessment 
Added new section and referred 
to master protocol  
To align content of protocol 
with that of GSK standard 
template 
Section 3 Study Objectives and 
Endpoints 
Revised PK endpoint 
To describe the parameters 
constituting the endpoint 
measures. 
Section 6.3. Measures to 
Minimize Bias: Randomization 
and Blinding 
Added “non-randomized” 
To clarify study design 
Section 6.4. Study Treatment 
Compliance 
Added “dostarlimab and 
niraparib during dostarlimab 
infusion visits”. 
To clarify exactly what study 
treatment would be administered 
to the participant at the research 
site and when this treatment 
would be administered.  
Section 6.5 Dose Modification 
Added clarifying text 
To clarify that guidance in first 
paragraph of Section 6.5 is 
applicable to dostarlimab. To 
include reference to Section 4.7 
in the master protocol for full 
dose modification guidance. 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 68 of 74 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 6.8 Treatment 
Compliance 
Deleted this Section 
To remove text that had already 
been presented in the protocol in 
Section 6.4. 
Section 7.1.2 QTc Stopping 
Criteria 
Added new section on QTc 
stopping criteria referring to 
master protocol  
To align with safety monitoring 
requirements for dostarlimab 
Section 8.1.2 Secondary 
Efficacy Endpoint 
Added text for scan data 
collection 
To establish that while scan data 
are not routinely collected in the 
study, these data may be 
collected under special 
circumstances. 
Section 8.4 Pharmacokinetics, 
Immunogenicity and 
Biomarkers 
• 
Added text from Master 
protocol Section 8.4 on PK 
sampling. 
To provide additional detail in 
this supplement protocol on PK 
sampling requirements.  
Section 9.3.3 Secondary 
Endpoints, Section 9.3.4 Interim 
Analysis, and Section 9.3.5 
Exploratory Analysis 
Reordered sections / subsections 
Reordered sections/ subsections 
to more clearly present planned 
analyses. 
Amendment 04 (23 May 2024) 
Overall Rationale for Amendment 04: 
Amendment 04 is a global amendment resulting in changes in participant dosing based on the 
participant’s age. Administrative, editorial, and clarifications for study conduct are also included. 
A general description and brief rationale(s) for key changes are provided in Table 2 below. The 
synopsis was also updated to align with the changes in the protocol body. 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 69 of 74 
Table 2 
Summary of Changes for Amendment 04 
Section(s) Affected 
Description of Change 
Brief Rationale 
Headers, Title Page, abbreviations, 
Protocol Amendment Summary of 
Changes, List of Abbreviations, 
Appendices, References, and 
throughout 
Section 6 Study Treatments and 
Concomitant Therapy 
Headers and title page updated with 
new document numbers, dates, and 
amendment information; Protocol 
Amendment Summary of Changes 
section was updated to include details 
and rationales for this amendment; 
administrative changes, abbreviation 
updates, editorial revisions for 
consistency with Sponsor’s ways of 
working, minor corrections and 
formatting adjustments, and to add 
clarification and/or remove 
discrepancies 
Editorial changes to align with the 
Sponsor’s standard protocol template, 
style guide, ways of working, regulatory 
requirements, and for accuracy, clarity, 
conformity, flow, and typographical 
error correction. 
Throughout 
• Use of 
 changed to 
 
throughout the document including 
 details and use of 
 going 
forward 
 is the selected 
 
 developed by 
the applicant for use in participants and 
is a term commonly used by the 
Sponsor’s formulation development and 
manufacturing groups 
Section 1.3 Schedule of Assessments 
(Table 3, footnote) 
Section 1.2 Schemas, Figure 1 (new) 
Section 2 Introduction 
Section 3, Table 5: Objectives and 
Endpoints for Study 213406 
Section 4.1 Overall Design 
Section 4.1.1 Dose Limiting Toxicity 
Section 4.2 Number of Participants 
Section 4.4 Dose Adjustment Criteria 
Section 4.4.1 Dose Adjustment Criteria 
for Age and Weight 
Section 4.4.2 Dose Adjustments for 
Adverse Events 
Section 4.4.3 Niraparib 
Section 4.4.4 Dostarlimab 
Section 5.1 Participant Inclusion 
Criterion 
Section 6.1 Study Treatments 
Administered 
Table 9: Investigational Products 
Section 8.1 Assessment of Efficacy 
Section 9.1 Sample Size Determination 
Section 9.2 Analysis Populations 
Section 9.3.2 Primary Endpoints 
Section 9.3.3 Secondary Endpoints 
• New figure outlining Part 2 study 
design 
• Footnotes updated in SoA regarding 
monitoring/PK sample collection with 
changes in niraparib doses in new 
proposed niraparib dosing regimens 
• Introduction and study objectives and 
endpoints updated to include the 
Safety Run-in Cohort 
• Update overall design to reflect 
updated dosing and details of Safety 
Run-in 
• DLT criteria for Part 2 included in new 
section  
• Number of participants updated to 
include Safety Run-in Cohort 
participants 
• Section 4.4.1 and Section 4.4.2 
added outlining dose adjustments for 
age and weight and AEs  
• Section 4.4.3 included for guidance 
on niraparib dose reductions and 
Table 6, Table 7, and Table 8 added 
outlining modifications for AEs, 
nonhematologic adverse reactions, 
and haematologic adverse reactions, 
respectively  
• Subsection included for dostarlimab 
dose modification 
• Inclusion Criterion #3 updated to 
outline age enrolment requirements 
under Amendment 04 
Changes to proposed dosing regimens 
for niraparib and study design, following 
study enrolment pause and data 
evaluation to ensure appropriate dosing 
of participants with the combination, 
including additional cohorts to evaluate 
additional dose levels 
Minor editorial changes to endpoints 
and objectives for clarification. 
CCI
CCI
CCI
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 70 of 74 
Section(s) Affected 
Description of Change 
Brief Rationale 
• Inclusion criterion #4 – updated to 
reflect no requirement for ability to 
swallow as a result of 
 
formulation being used going forward 
• Study treatment information sections 
update to include 
 details 
including update to Investigation 
products table that also included 
updates to align with regulatory 
requirements 
• Sample size text updated to reflect 
addition of Safety Run-in 
• Updated assessment of efficacy 
section and statistical analyses 
sections to include Safety Run-in 
information and definition for DTL-
evaluable Population 
Section 3, Table 5 Objectives and 
Endpoints for Study 213406 
Section 9.3.5 Exploratory analyses 
• Exploratory endpoints updated to 
adjust wording for exploratory 
biomarker objective and endpoint 
language, as well as analyses 
To provide further details and more 
clarity about the planned exploratory 
analysis.  
Section 5.1 Participant Inclusion 
Criteria 
• Inclusion criterion #6: organ function 
parameters updated for haemoglobin  
To align with the patient population 
Section 1.3 Schedule of Assessments 
(Table 3, footnote) 
Section 5.1 Participant Inclusion 
Criteria (criterion #7c) 
• Clarification included that WOCBP 
must have a pregnancy test even if 
they had received treatment that 
potentially but not definitely would 
prohibit becoming pregnant 
• Timeline for providing negative 
pregnancy test result updated to 24 
hours 
Updated to increase assurance that 
female participant of childbearing 
potential is not pregnant as close as 
possible to time of study drug dosing 
Section 5.2 Participant Exclusion 
Criteria 
• Exclusion criterion #7 – clarification 
participants with previously treated 
CNS metastases for evidence of 
disease progression, for evidence of 
disease progression  
Updated text to provide more accurate 
description of changes indicative of 
progression of disease in brain. 
Section 5.2 Participant Exclusion 
Criteria 
• Exclusion criterion #11 - updated 
language regarding when 
breastfeeding can resume 
To align with guidance in current US 
prescribing information for niraparib 
and dostarlimab 
Section 5.2. Participant Exclusion 
Criteria 
• Exclusion criterion 14 – updated 
wording regarding HbsAg/HbcAb for 
HBV screening 
To permit the inclusion of patients with 
past HBV infection 
Section 5.2. Participant Exclusion 
Criteria 
• New exclusion criteria #25 and #26 
added regarding HCV testing  
To align with current protocol template 
language 
Section 5.2. Participant Exclusion 
Criteria 
• Exclusion criterion #17 – updated 
language regarding AEs in 
participants undergoing systemic 
anticancer therapy with exceptions as 
agreed with Sponsor.  
Expansion of text to more clearly define 
conditions for participant eligibility.  
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 71 of 74 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 1.3 Schedule of Assessments 
(Table 3, including footnotes)  
Section 2.2 Rationale for Tumour Type 
• 
 
Editorial change for clarification 
Section 5.1. Participant Inclusion 
Criteria 
• Inclusion criterion #1 - Replaced 
statement ‘local curative treatment.' 
with ‘alternative curative treatment.' 
Clarification 
Section 5.1 Participant Inclusion 
Criteria 
• Inclusion criterion #10 – updated 
clarifying tumour tissue sample 
requirements and decalcification for 
bone samples 
Clarification 
Section 1.3. Schedule of Activities 
(Table 3, including footnote) 
Section 4.4 General Study Conduct 
Section 8.4 Pharmacokinetics, 
Immunogenicity, and Biomarkers 
• Update to blood sample collection for 
niraparib PK  
• Adjusted table and added clarifying 
footnote for blood sampling for 
dostarlimab PK and/or ADAs and 
neutralising antibodies (NAb) at 
Safety FUP Visit and FUP 
Assessment Period 
• Updated language regarding 
collection of blood samples and 
storage 
Clarification for study conduct and 
alignment with Sponsor requirements 
for sample storage 
Section 1.3 Schedule of Assessments 
(Table 3 and Table 4; including 
footnotes) 
Table 4 Tumour Assessment Flowchart 
• Clarification that brain scans must 
include IV contrast and brain scan by 
MRI preferred to that by CT including 
in table footnote and Table 4 outlining 
tumour assessments 
• Wording and footnote updates in SoA 
for clarifications including aligning 
discontinuation wording throughout 
Clarification for study conduct. 
Section 1.3 Schedule of Assessments 
(SoA) footnote 
Section 8.2 Assessment of Safety 
Section 8.4 Pharmacokinetics, 
Immunogenicity, and Biomarkers 
• Detail included regarding prioritisation 
of blood sample collection in the 
event of concerns for excessive blood 
volume withdrawal 
Clarification for study conduct to 
provide guidance to sites on relative 
importance of collection of specific 
blood samples  
Section 1.3 Schedule of Assessments 
(SoA) including footnote 
Section 8.4.1 Exploratory biomarkers 
• Updated language regarding 
collection and analysis of biomarker 
samples and processing  
Clarification 
Section 1.3. Schedule of Activities 
(Table 3, including footnotes) 
• Updated timing for collection of vital 
signs, height, and weight 
measurements including during 
follow-up period and clarifications for 
measuring height and weight 
• 
 
 
 
  
Clarification for study conduct, including 
adjusted language to permit consistent 
monitoring of vital signs throughout the 
Treatment Period. 
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 72 of 74 
Section(s) Affected 
Description of Change 
Brief Rationale 
• Adjusted wording surrounding 
collection and follow-up of nonserious 
AEs, and expectations for follow-up of 
SAEs during long-term Follow-up 
Period and when starting alternative 
anticancer therapy 
Section 8.5 Genetics 
• Updated language outlining DNA 
analysis 
Clarification 
Abbreviations: 
 ADA=antidrug antibody(ies); AE=adverse event; 
 
; CBC=complete blood count; CNS=central nervous system; CT=computed tomography; DLT=dose limiting 
toxicity(ies); FUP=follow-up; GFR=glomerular filtration rate; HbcAb=hepatitis B core antibody, HBsAg = hepatitis B surface 
antigen; HBV = hepatitis B virus; HCV=hepatitis C virus; MRI=magnetic resonance imaging; PK=pharmacokinetics; 
RECIST=Response Evaluation Criteria in Solid Tumours; SAE(s)= serious AE(s); SoA=schedule of assessments; 
; WOCBP=woman of childbearing potential; US=United States.  
 
Amendment 04 GBR-1(08 Aug 2024) 
Overall Rationale for Amendment 04 GBR-1: 
Amendment 04 GBR-1 is a UK-specific amendment addressing agency feedback regarding 
exclusion criterion 17. A description and rationale for the changes is provided in Table 2 below 
 
Table 2: Summary of Changes for Amendment 04 GBR-1 
Section(s) Affected 
Description of Change (deleted text; added text) 
Brief Rationale 
Headers, Title Page, Protocol 
Amendment Summary of Changes, 
Appendix 2 Country-specific 
Requirements 
Headers and title page updated with new amendment 
number/approval date, and amendment information; 
Protocol Amendment Summary of Changes section 
was updated to include details and rationale for this 
amendment; country-specific appendix for global 
amendments removed and associated text in protocol 
sections/tables adjusted. 
Editorial changes to align 
with the Sponsor’s 
standard protocol 
template, style guide, 
ways of working. 
Synopsis 
Section 5.2 Participant Exclusion 
Criteria 
Exclusion criterion #17 updated as follows: 
Participant has not recovered (i.e., to Grade ≤1 or to 
baseline) from systemic anticancer therapy-induced 
AEs. Note: Participants with certain AEs that are 
considered either nonclinically significant or are 
deemed stable or irreversible are exceptions to this 
criterion and may qualify for the study after discussion 
with the GSK Medical Monitor. Examples of AEs 
include, but are not limited to, alopecia, hearing 
impairment, alopecia, Grade ≤2 neuropathy, 
Grade ≤2 fatigue, Grade ≤2 anaemia, and/or 
Grade ≤2 neutropenia are an exception to this 
criterion and may qualify for the study. 
Regulatory agency 
feedback. 
 
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 73 of 74 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement A 
Protocol Amendment 05 
Page 74 of 74 
12. 
LIST OF REFERENCES 
Bielack SS, Kempf-Bielack B, Branscheid D, Carrle D, Friedel G, Helmke K, et al. Second and 
subsequent recurrences of osteosarcoma: presentation, treatment, and outcomes of 249 
consecutive cooperative osteosarcoma study group patients. J Clin Oncol. 2009;27(4):557-565. 
 
Clopper C and Pearson ES. The use of confidence or fiducial limits illustrated in the case of the 
binomial. Biometrika. 1934;26:404-413. 
 
Lagmay JP, Krailo MD, Dang H, Kim A, Hawkins DS, Beaty O, 3rd, et al. Outcome of Patients 
With Recurrent Osteosarcoma Enrolled in Seven Phase II Trials Through Children's Cancer 
Group, Pediatric Oncology Group, and Children's Oncology Group: Learning From the Past to 
Move Forward. J Clin Oncol. 2016;34(25):3031-3038. 
 
Steliarova-Foucher E, Colombet M, Ries LAG, Moreno F, Dolya A, Bray F, et al. International 
incidence of childhood cancer, 2001-10: a population-based registry study. Lancet Oncol. 
2017;18(6):719-731. 

Signature Page for  213406 TMF-20143923 v1.0
Signature Page for TMF-20143923 v1.0
Reason for signing: Approved
Name:
Role: Approver
Date of signature: 17-Dec-2024 15:54:13 GMT+0000
PPD

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 1 of 75 
TITLE PAGE 
SUPPLEMENT B 
PROTOCOL 213406 
PART 2: NEUROBLASTOMA EXPANSION COHORT 
Protocol Title: 
A PHASE 1, MULTICENTRE, OPEN-LABEL, DOSE 
ESCALATION AND COHORT EXPANSION STUDY OF 
NIRAPARIB AND DOSTARLIMAB IN PAEDIATRIC 
PATIENTS WITH RECURRENT OR REFRACTORY 
SOLID TUMOURS 
Protocol Number: 
213406 Amendment 05 
Compound Number or Name:  Niraparib (GSK3985771), Dostarlimab (GSK4057190A) 
Brief Title: 
Dose Escalation and Cohort Expansion Study of Niraparib 
and Dostarlimab in Paediatric Participants With Solid 
Tumours 
Study Phase: 
Phase 1 
Sponsor Name and Legal 
Registered Address: 
 
 
 
 
Medical Monitor Name and 
Contact Information: 
GlaxoSmithKline Research & Development Limited  
79 New Oxford Street 
London 
WC1A 1DG 
United Kingdom  
 
Contact Information can be found in local study contact 
information 
Sponsor Signatory: 
 
 
Nidale Tarek, MD 
Senior Medical Director 
GSK 
Regulatory Agency 
Identifying Number(s): 
EudraCT Number: 2020‐002359‐39 
EU CT: 2024-511071-16 
Approval Date:  
17 Dec 2024 
Copyright 2024 the GSK group of companies. All rights reserved. Unauthorised copying or use 
of this information is prohibited. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 2 of 75 
PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Table 1: 
Document History 
Document 
Date 
Amendment 05 
17 Dec 2024 
Amendment 04 GBR-1 
08 August 2024 
Amendment 04 
23 May 2024 
Amendment 03 
20 July 2022 
Amendment 02 
23 November 2020 
Amendment 01 
16 October 2020 
Original Protocol 
12 May 2020 
Amendment 05 (17 Dec 2024) 
Overall rationale for the current Amendment:  
Protocol Amendment 05 is a substantial amendment that aligns Protocol Amendment 04 with all 
aspects of the UK-specific Protocol Amendment 04 GBR-1, resulting in a single global 
amendment.  Additional changes include an update of the sponsor’s legal registered address plus 
administrative and editorial updates and clarifications for study conduct. 
A general description and brief rationale(s) for key changes are provided in Table 2 below. The 
synopsis was also updated to align with the changes in the protocol body, where applicable. 
Table 2 
List of main changes in the protocol and their rationale: 
 
Section # and title 
Description of change 
Brief rationale 
Title Page 
Sponsor legal address update 
To align with current GSK policy 
Section 1.1 Synopsis Methodology] 
Section 4.1 Overall Study Design 
Language updated to indicate that 
the dose escalation committee (DEC) 
will review safety data and will 
determine future enrollment plan 
To more clearly describe the role of the 
DEC in safety data review process 
overall  
Section 1.1 Synopsis 
Main Criteria for Inclusion; Section 5.1 
Participant Inclusion Criteria Point 03 
Addition of relevant time point (“at 
screening”) 
To clearly indicate at what point in the 
study disease characteristics were to be 
evaluated  
Section 1.1 Synopsis 
Main Criteria for Exclusion; Section 5.2 
Participant Exclusion Criteria Point 17 
Participant has not recovered (i.e., to 
Grade ≤1 or to baseline) from prior 
systemic anticancer therapy-induced 
AEs. Note: Participants with alopecia, 
hearing impairment, Grade ≤2 
neuropathy, Grade ≤2 fatigue, Grade 
≤2 anaemia, and/or Grade ≤2 
neutropenia are an exception to this 
To revert the wording to that in Protocol 
Amendment 04, which provided more 
specific criteria for enrollment of 
participants with ongoing toxicities.   

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 3 of 75 
Section # and title 
Description of change 
Brief rationale 
criterion and may qualify for 
participation in the study. 
Section 1.3 Schedule of Activities (SoA) 
Footnote x 
“Cycle 1 Day 1 2.5 hour samples 
must be collected at the scheduled 
time ±0.5 hour” was added 
To more specifically define the permitted 
sample collection window 
Section 1.3 Table 3 Schedule of 
Activities 
Table 4 Tumor Assessment Flowchart 
Addition of text indicating bone 
marrow evaluation is required for all 
participants to confirm response. 
To clarify timing of required bone marrow 
assessments during response evaluation 
Section 1.1 Synopsis Objectives 
Section 3 STUDY OBJECTIVES AND 
PURPOSE Table 5    
Text was added to Part 2 Safety Run-
in Secondary Objective for general 
standard safety objective  
To ensure that all safety data were 
assessed in Part 2 Safety Run-in not just 
DLTs and events of Grade ≥3 
thrombocytopenia 
Throughout document 
Minor corrections and formatting 
adjustments were made 
To add clarification and increase 
readability 
 
 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 4 of 75 
TABLE OF CONTENTS 
1. 
PROTOCOL SUMMARY ............................................................................................8 
1.1. 
Synopsis ........................................................................................................................8 
1.2. 
Schemas ......................................................................................................................18 
1.3. 
Schedule of Activities (SoA) ......................................................................................18 
2. 
INTRODUCTION ......................................................................................................28 
2.1. 
Background .................................................................................................................28 
2.1.1. 
Background of Niraparib ............................................................................................28 
2.1.2. 
Background of Dostarlimab ........................................................................................28 
2.1.3. 
Rationale for Synergy Between PARP Inhibitors and Immune Checkpoint 
Inhibitors .....................................................................................................................28 
2.2. 
Rationale for Tumour Type ........................................................................................28 
2.3. 
Rationale for Current Study ........................................................................................28 
2.4. 
Benefit Risk Assessment ............................................................................................28 
3. 
STUDY OBJECTIVES AND PURPOSE ..................................................................29 
4. 
INVESTIGATIONAL PLAN .....................................................................................32 
4.1. 
Overall Study Design ..................................................................................................32 
4.1.1. 
Dose Limiting Toxicity ...............................................................................................33 
4.2. 
Number of Participants ...............................................................................................35 
4.3. 
Treatment Assignment ................................................................................................35 
4.4. 
Dose Adjustment Criteria ...........................................................................................35 
4.4.1. 
Dose Adjustment Criteria for Age and Weight ..........................................................35 
4.4.2. 
Dose Adjustment for Adverse Events .........................................................................35 
4.4.3. 
Niraparib .....................................................................................................................35 
4.4.4. 
Dostarlimab .................................................................................................................38 
4.5. 
Criteria for Study Termination ...................................................................................38 
4.6. 
End of Study Definition ..............................................................................................38 
4.7. 
Study Conduct ............................................................................................................38 
4.7.1. 
Procedures by Visit .....................................................................................................38 
4.7.2. 
General Guidance for Treatment Continuity when Participants are Unable to 
Come into the Clinic ...................................................................................................38 
5. 
STUDY POPULATION .............................................................................................40 
5.1. 
Participant Inclusion Criteria ......................................................................................40 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 5 of 75 
5.2. 
Participant Exclusion Criteria .....................................................................................42 
5.3. 
Lifestyle Considerations .............................................................................................45 
5.4. 
Screen Failures ............................................................................................................45 
6. 
STUDY TREATMENT(S) AND CONCOMITANT THERAPY .............................46 
6.1. 
Study Treatment(s) Administered ...............................................................................46 
6.2. 
Preparation/Handling/Storage/Accountability ............................................................48 
6.2.1. 
Study Treatment Packaging and Labelling .................................................................48 
6.2.2. 
Study Treatment Storage ............................................................................................48 
6.2.3. 
Administration ............................................................................................................48 
6.2.4. 
Study Treatment Accountability .................................................................................48 
6.2.5. 
Study Treatment Handling and Disposal ....................................................................48 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................................48 
6.4. 
Study Treatment Compliance .....................................................................................48 
6.5. 
Dose Modification ......................................................................................................48 
6.6. 
Treatment of Overdose ...............................................................................................48 
6.7. 
Concomitant Therapy .................................................................................................48 
6.7.1. 
Rescue Medications ....................................................................................................49 
6.7.2. 
Prohibited Medications ...............................................................................................49 
6.7.3. 
Other Study Restrictions .............................................................................................49 
7. 
DISCONTINUATION OF STUDY TREATMENT AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................50 
7.1. 
Discontinuation of Study Treatment ...........................................................................50 
7.1.1. 
Liver Chemistry Stopping Criteria .............................................................................50 
7.1.2. 
QTc Stopping Criteria .................................................................................................50 
7.2. 
Withdrawal of Consent ...............................................................................................50 
7.3. 
Participant Discontinuation/Withdrawal from the Study ...........................................50 
7.4. 
Lost to Follow-Up.......................................................................................................50 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................51 
8.1. 
Assessment of Efficacy ...............................................................................................51 
8.1.1. 
Primary Efficacy Endpoint for the Neuroblastoma Cohort Expansion ......................51 
8.1.2. 
Secondary Efficacy Endpoints for the Neuroblastoma Cohort Expansion .................51 
...........................................................51 
8.2. 
Assessment of Safety ..................................................................................................51 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 6 of 75 
8.2.1. 
Safety Parameters .......................................................................................................52 
8.3. 
Adverse Events and Serious Adverse Events .............................................................52 
8.4. 
Pharmacokinetics, Immunogenicity, and Biomarkers ................................................52 
............................................................................................52 
............................................................................................53 
8.6. 
Health Economics .......................................................................................................53 
9. 
STATISTICAL CONSIDERATIONS .......................................................................54 
9.1. 
Sample Size Determination ........................................................................................54 
9.2. 
Analysis Populations ..................................................................................................55 
9.3. 
Statistical Analyses .....................................................................................................56 
9.3.1. 
General Considerations ...............................................................................................56 
9.3.2. 
Primary Endpoints ......................................................................................................56 
9.3.3. 
Secondary Endpoints ..................................................................................................56 
............................57 
............................57 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................58 
11. 
APPENDICES ............................................................................................................59 
12. 
LIST OF REFERENCES ............................................................................................75 
 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 7 of 75 
LIST OF TABLES 
Table 1: 
Document History .........................................................................................................2 
Table 2 
List of main changes in the protocol and their rationale: .............................................2 
Table 3: 
Schedule of Activities .................................................................................................19 
Table 4: 
Tumour Assessment Flowchart ..................................................................................26 
Table 5: 
Objectives and Endpoints for Study 213406 Neuroblastoma Cohort .........................29 
....................................................36 
Table 7: 
Niraparib Dose Modifications for Nonhaematologic Adverse Reactions ..................36 
Table 8: 
Niraparib Dose Modifications for Haematologic Adverse Reactions ........................37 
Table 9: 
Investigational Products ..............................................................................................47 
Table 10: Analysis Sets ...............................................................................................................55 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 8 of 75 
1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Name of Sponsor/Company: GSK 
Name of Investigational Product: Niraparib, dostarlimab 
Name of Active Ingredient: Niraparib, dostarlimab 
Title of Study: A Phase 1, Multicentre, Open-label, Dose escalation and Cohort Expansion Study of 
Niraparib and Dostarlimab in Paediatric Patients with Recurrent or Refractory Solid Tumours 
Part 2: Neuroblastoma Expansion Cohort 
Study Centre(s): Multicentre  
Phase of Development: 
Phase 1 
Objectives: 
The following are the objectives for the Safety Run-in Cohort and Neuroblastoma Expansion Cohort of 
this study. 
Part 2 Safety Run-In  
Primary: 
The primary objective of this cohort is as follows: 
• 
to assess the safety and tolerability of the 
 
 by assessing dose limiting toxicity (DLT) and Grade ≥3 
thrombocytopenia adverse events (AEs) in paediatric participants 
Secondary: 
The secondary objectives of this cohort are as follows: 
• 
to evaluate additional measures of anticancer activity, including objective response rate 
(ORR), duration of response (DOR), disease control rate (DCR), and progression-free 
survival (PFS) in paediatric participants 
• 
to characterise the pharmacokinetics (PK) of niraparib in paediatric participants 
• 
to evaluate the safety of the combination 
 
 in paediatric participants 
Part 2 Expansion 
Primary: 
The primary objective of this cohort is as follows: 
• 
to assess the antitumour activity of the combination of niraparib and dostarlimab, assessed 
primarily by ORR (using International Neuroblastoma Response Criteria [INRC]) in paediatric 
participants 
 
 
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 9 of 75 
Secondary: 
The secondary objectives of this cohort are as follows: 
• 
to evaluate additional measures of anticancer activity, including DOR, DCR, and PFS in 
paediatric participants 
• 
to evaluate the safety of the combination of 
 in 
paediatric participants 
• 
to characterise the pharmacokinetics (PK) of the combination of niraparib and dostarlimab in 
paediatric participants 
• 
to assess the immunogenicity of dostarlimab in paediatric participants 
• 
 
 
Methodology: 
The overall study design and conduct are described in the master protocol. 
 
 
 
 
  
 
 
 
 
 
 This modification is included in Protocol Amendment 05. 
 
 
 
 
 
. Study treatment may continue 
until progressive disease (PD), unacceptable toxicity, participant withdrawal, Investigator’s decision, 
or death. See Figure 1 for Part 2 study design. 
Under Protocol Amendment 05, enrolment in Part 2 will start with a Safety Run-in Cohort to confirm 
the safety, tolerability, and preliminary efficacy of the 
 
 in participants with osteosarcoma and neuroblastoma. A total of 8 DLT-evaluable 
participants will be enrolled in the Safety Run-in, with no more than 5 out of 8 evaluable participants 
having the same tumour type. Participants in the Safety Run-in will be observed for a minimum of 42 
days (2 cycles, DLT evaluation period) for DLTs and Grade≥3 thrombocytopenia. Participants in the 
Safety Run-in will be dosed in a staggered fashion, meaning no more than 3 participants will be 
allowed to receive the study treatment until each dosed participant has completed at least 2 cycles of 
study treatment and the resulting data from all 3 dosed participants have been reviewed. This is to 
ensure an adequate interval for observation and assessment of tolerability of the 
 
  
CCI
CCI
CCI
CCI
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 10 of 75 
• 
If DLTs or Grade ≥3 thrombocytopenia are observed in ≤1 participant out of the first 3 dosed 
participants and it is deemed safe to proceed by the study team, additional participants will be 
enrolled for up to 8 DLT-evaluable participants. 
• 
If DLTs or Grade ≥3 thrombocytopenia are observed in ≥2 participants out of the first 3 dosed 
participants, the Part 2 Safety Run-in Cohort will be paused. Review of safety data and 
available PK data and determination of the dosing strategy for subsequent participants will be 
completed by the Dose Escalation Committee (DEC; see Appendix 1 of the master protocol for 
details regarding the DEC). 
• 
The Part 2 Expansion Cohort will be initiated if 2 or less DLTs and 2 or less Grade ≥3 
thrombocytopenia events are observed out of 8 DLT-evaluable participants.  
• 
The Safety Run-in will be paused if 2 or less DLTs and 3 Grade ≥3 thrombocytopenia events 
are observed out of 8 DLT-evaluable participants. 
• 
If DLTs are observed in 3 of 8 participants or Grade ≥3 thrombocytopenia is observed in 4 of 8 
participants, 
 
 in the Safety Run-in Cohort would be considered intolerable.  
Once all participants in the Safety Run-in have been observed for ≥42 days, all available data from the 
Part 2 Safety Run-in together with all data previously collected under Protocol Amendment 04 and 
earlier will be reviewed by the study DEC and the Data Review Committee (DRC) before additional 
participants on Part 2 are enrolled.  
Further details are provided in protocol Section 4.1, including details of the DLTs.  
Following the Safety Run-in, if the 
 is deemed safe, up to 30 
evaluable participants may enrol in the Part 2 Cohort Expansion for neuroblastoma, inclusive of any 
eligible participants with neuroblastoma treated in the Part 2 Safety Run-in. Enrolment into the Part 2 
Cohort Expansion will be conducted according to a Simon’s 2-stage optimal design in which ≥2 of the 
first 10 evaluable participants must experience an objective tumour response (as assessed by the 
Investigator using INRC) before accrual of the remaining 20 participants.  
 
 
 
 
 
 
  
 
 
General study conduct is described in the master protocol. 
 
 
 
 
Data Review Committee 
A DRC will be established for the purpose of monitoring safety and efficacy data from the Safety Run-
in and Cohort Expansion part of the study (Part 2). This committee will be composed of GSK staff who 
are independent of all aspects of the study. Members will include a clinical development physician, a 
safety physician, and a statistician. This committee will convene both periodically and on an ad hoc 
basis, as mandated by emerging study data. Comprehensive details of committee membership and its 
activities will be described in a formal charter. 
CCI
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 11 of 75 
Number of Participants (Planned): Safety Run-in: approximately 8 DLT-evaluable participants in 
total across osteosarcoma (Part 2A) and neuroblastoma (Part 2B).  
Part 2 Expansion: approximately 30 participants with neuroblastoma are planned for enrolment in this 
cohort (including eligible participants with neuroblastoma from the Safety Run-in). See Section 9.1 for 
eligibility requirements for enrolment of Safety Run-in participants into the Part 2 Cohort Expansion. 
Diagnosis and Main Criteria for Inclusion: 
Participant will be eligible for the Safety Run-in and Neuroblastoma Expansion Cohorts of Part 2 if all 
of the following criteria are met: 
1. 
 
 
 
2. Participant with neuroblastoma has measurable/evaluable disease by INRC at screening. 
Participants with recurrent/relapsed bone metastasis that is metaiodobenzylguanidine (MIBG)-
positive (or FDG-positive, for MIBG-nonavid tumours) as only site of disease are eligible. 
5. Performance status must be ≥60% on the Karnofsky scale for participants >16 years of age and 
≥60% on the Lansky scale for participants ≤16 years of age. 
Note: Neurologic deficits in participants with brain metastases must have been stable for at 
least 7 days prior to study enrolment. Participants who are unable to walk because of paralysis, 
but who are upright in a wheelchair, will be considered ambulatory for the purpose of 
assessing the performance status. 
6. Participant has adequate organ function, defined as follows: 
Note: The participant must not have received blood transfusion, growth factors, or platelet 
stimulating agents in the 14 days prior to providing a sample for haematologic analysis nor 
erythropoietin in the prior 6 weeks. 
a. absolute neutrophil count ≥1000/μL 
b. platelets ≥100 000/μL 
c. haemoglobin ≥8 g/dL or ≥5.0 mmol/L 
d. serum creatinine≤1.5×upper limit of normal (ULN) for age or calculated creatinine 
clearance or radioisotope glomerular filtration rate ≥60 mL/min/1.73m2 
e. total bilirubin ≤1.5 × ULN or direct bilirubin ≤1 × ULN 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 12 of 75 
f. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN 
unless liver metastases are present, in which case AST and ALT must be ≤5 × ULN 
g. international normalised ratio or prothrombin time (PT) ≤1.5 × ULN unless the 
participant is receiving anticoagulant therapy, as long as PT or partial thromboplastin 
time (PTT) is within therapeutic range of intended use of anticoagulants 
h. activated PTT ≤1.5 × ULN unless the participant is receiving anticoagulant therapy, as 
long as PT or PTT is within therapeutic range of intended use of anticoagulants 
7. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at 
least one of the following conditions applies: 
a. Is not a woman of childbearing potential (WOCBP). 
Or 
b. 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 
3 of the master protocol, from the Screening Visit through at least 180 days after the 
last dose of study treatment and agrees not to donate eggs (ova, oocytes) for the 
purpose of reproduction during this period. The Investigator should evaluate the 
effectiveness of the contraceptive method in relationship to the first dose of study 
treatment. 
c. A WOCBP must have a negative highly sensitive pregnancy test (urine or serum, as 
required by local regulations) within 24 hours prior to the first dose of study treatment 
and irrespective of prior medical treatment. 
Additional requirements for pregnancy testing during and after the Treatment Period are 
located in the master protocol. 
The Investigator is responsible for review of medical history, menstrual history, and recent 
sexual activity to decrease the risk for inclusion of a woman with an early undetected 
pregnancy. 
8. A male participant of reproductive potential is eligible to participate if he agrees to the 
following starting with the first dose of study treatment through at least 90 days (a 
spermatogenesis cycle) after the last dose of study treatment: 
a. refrain from donating sperm 
plus, either: 
b. be abstinent from heterosexual intercourse as their preferred and usual lifestyle 
(abstinent on a long-term and persistent basis) and agree to remain abstinent 
or 
c. must agree to use a male condom and should also be advised of the benefit for a 
female partner to use a highly effective method of contraception, as a condom may 
break or leak, when having sexual intercourse with a WOCBP who is not currently 
pregnant 
9. The Investigator, or a person designated by the Investigator, will obtain written informed 
consent from each study participant or the participant’s legally acceptable representative, 
parent(s), or legal guardian and the participant’s assent, when applicable, before any study-
specific activity is performed. The Investigator will retain the original copy of each 
participant’s signed consent/assent document. 
10. 
 
 
 
 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 13 of 75 
 
 
 
 
  
Main Criteria for Exclusion: 
Participant will not be eligible for study entry if any of the following criteria are met: 
1. Participation presents unacceptable risk to the prospective participant based on the 
Investigator’s judgement. 
2. Participant has known hypersensitivity to dostarlimab or niraparib, their components, or their 
excipients. 
3. Participant has received prior therapy with an anti-PD-1, anti-programmed cell death-ligand 1, 
anti-programmed cell death-ligand 2, anticytotoxic T-lymphocyte-associated antigen-4 
antibody (including ipilimumab), or any other antibody or drug specifically targeting T-cell co-
stimulation or checkpoint pathways (with the exception of participants rolling over from Part 1 
of the study: these participants are allowed to have received dostarlimab). 
4. Participant has had prior treatment with a known PARP inhibitor (with the exception of 
participants rolling over from Part 1 of the study: these participants are allowed to have 
received niraparib). 
5. Participant has a known history of myelodysplastic syndrome or acute myeloid leukaemia. 
6. Participant has active autoimmune disease that has required systemic treatment in the past 
2 years (ie, with use of disease-modifying antirheumatic drugs, corticosteroids, or 
immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic 
corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a 
form of systemic treatment. 
7. Participant has known active central nervous system (CNS) metastases, carcinomatous 
meningitis, or both. Note: Participants with previously treated brain metastases may participate 
provided they are clinically stable and have no evidence of new, enlarging, or progressing 
brain metastases (using the identical imaging modality for each assessment, either MRI or CT 
scan) for at least 4 weeks (28 days) prior to the first dose of study treatment. In addition, the 
participant must not have been using steroids for at least 7 days prior to the first dose of study 
treatment. Carcinomatous meningitis precludes a participant from study participation 
regardless of clinical stability. 
8. Participant had a known additional (second primary) malignancy that progressed or required 
active treatment within the last 2 years. 
9. Participant is considered a poor medical risk due to a serious, uncontrolled medical disorder, 
nonmalignant systemic disease, or active infection that requires systemic therapy. Specific 
examples include, but are not limited to, history of (noninfectious) pneumonitis that required 
steroids or current pneumonitis, uncontrolled ventricular arrhythmia, uncontrolled major 
seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any 
psychiatric or substance abuse disorders that would interfere with cooperation with the 
requirements of the study (including obtaining assent/consent). 
10. Participant has a condition (such as transfusion-dependent anaemia or thrombocytopenia), 
requirement for therapy, or laboratory abnormality that might confound the study results or 
interfere with the participant’s participation for the full duration of the study treatment. 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 14 of 75 
11. Participant is pregnant, breastfeeding, or expecting to conceive within the projected duration of 
the study, starting with the Screening Visit through 180 days after the last dose of study 
treatment. 
No data are available regarding the presence of dostarlimab or niraparib or its metabolites in 
human milk, or on its effects on the breastfed infant or milk production. Because of the 
potential for serious adverse reactions in breastfed infants from dostarlimab and/or niraparib, 
female participants should not breastfeed during treatment with dostarlimab and/or niraparib 
and for at least 4 months after the last dose of dostarlimab or at least 30 days after the last dose 
of niraparib, whichever is longer. 
12. Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or 
any other form of immunosuppressive therapy within 7 days prior to the first dose of study 
treatment. 
13. Participant has a known history of HIV (type 1 or 2 antibodies). 
14. Participant has documented presence of HbsAg and/or HBcAb at Screening or within 3 months 
prior to first dose of study intervention. Participants with a negative HbsAg and positive 
HbcAb result are eligible only if HBV DNA is negative (Appendix 12 of the master protocol) 
15. Participant must not have a gastrointestinal condition, such as bowel obstruction, that can 
impact absorption of oral medications and is identified by clinical symptoms or CT scan, etc. 
16. Participant has had any known Grade 3 or 4 anaemia, neutropenia, and/or thrombocytopenia 
that was related to the most recent prior anticancer treatment and that persisted >4 weeks 
(28 days). 
17. Participant has not recovered (ie, to Grade ≤1 or to baseline) from prior systemic therapy-
induced AEs. Note: Participants with alopecia, hearing impairment, Grade ≤2 neuropathy, 
Grade ≤2 fatigue, Grade ≤2 anaemia, and/or Grade ≤2 neutropenia are an exception to this 
criterion and may qualify for participation in the study. 
18. Participant had toxicity related to prior immunotherapy that led to treatment discontinuation. 
19. Participant had treatment with prior systemic anticancer therapy (investigational agent or 
device, or approved chemotherapy, targeted therapy, immunotherapy, or other systemic 
therapy) within the 3 weeks or 5 half-lives, whichever is shorter, prior to the first dose of study 
treatment, radiation therapy encompassing >20% of the bone marrow within 2 weeks prior to 
the first dose of study treatment, or any radiation therapy within 1 week prior to the first dose 
of study treatment. 
20. Participant has not recovered adequately from AEs or complications from any major surgery 
prior to starting study treatment. 
21. Participant has received a live vaccine within 30 days of planned start of study treatment. 
22. Participant has clinically significant cardiovascular disease (eg, significant cardiac conduction 
abnormalities, uncontrolled hypertension, cardiac arrhythmia or unstable angina, New York 
Heart Association Grade 2 or greater congestive heart failure, serious cardiac arrhythmia 
requiring medication, and history of cerebrovascular accident) within 6 months of enrolment. 
23. Participant has heart rate-corrected QT interval prolongation at Screening >450 msec or 
>480 msec for participants with bundle branch block. 
Notes: 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 15 of 75 
• 
The QTc is the QT interval corrected for heart rate according to Bazett’s formula 
(QTcB), Fridericia’s formula (QTcF), and/or another method, machine read or manually 
over read. 
• 
The specific formula that will be used to determine eligibility and discontinuation for an 
individual participant must be determined prior to initiation of the study and used 
consistently for eligibility and study assessments. 
24. Participant has received a solid organ transplant. 
25. Participant has a documented presence of HCV antibody at Screening or within 3 months prior 
to first dose of study intervention. NOTE: Participants with a positive HCV antibody test result 
due to prior resolved disease can be enrolled, only if a confirmatory HCV RNA test is negative 
and the participant otherwise meets entry criteria. 
26. Participant has documented presence of HCV RNA at Screening or within 3 months prior to 
first dose of study intervention. NOTE: The HCV RNA test is optional and participants with 
negative HCV antibody test are not required to undergo HCV RNA testing as well. 
Investigational Product, Dosage, and Mode of Administration: 
 Oral niraparib will be dispensed to 
participants on Day 1 of every 21-day treatment cycle beginning with Cycle 1 of the Treatment Period. 
 
  
A summary of study treatment administration is provided in the master protocol, and details are in the 
Pharmacy Manual. 
Duration of Treatment: Study treatment may continue until documented PD, unacceptable toxicity, 
participant withdrawal, Investigator’s decision, or death. 
Reference Therapy, Dosage, and Mode of Administration: 
Not applicable. 
Criteria for Evaluation: 
Part 2 Safety Run-in 
• 
DLTs during the first 42 days following the initiation of study treatment (i.e., approximately 
the first 2 treatment cycles). 
• 
Thrombocytopenia Grade ≥3 AEs during the first 42 days following initiation of study 
treatment (i.e., approximately the first 2 treatment cycles). 
• 
ORR is defined as the proportion of participants who have a best overall response (BOR) of 
confirmed complete response (CR) or partial response (PR) as determined by the Investigator 
using INRC for participants with neuroblastoma or RECIST v1.1 for participants with 
osteosarcoma. 
• 
DOR is defined as the time from first documentation of confirmed response (CR or PR) until 
the time of first documented PD by INRC for participants with neuroblastoma only or RECIST 
v1.1 for participants with osteosarcoma based on Investigator assessment or death (whichever 
occurs first). 
• 
DCR is defined as the proportion of participants who have achieved a BOR of confirmed CR, 
confirmed PR, or stable disease by INRC for participants with neuroblastoma or RECIST v1.1 
for participants with osteosarcoma based on Investigator assessment. 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 16 of 75 
• 
PFS is defined as the time from the date of the first dose of study treatment to the first 
documented PD, as determined by INRC for participants with neuroblastoma or RECIST v1.1 
for participants with osteosarcoma based on Investigator assessment, or death from any cause 
(whichever occurs first). 
Part 2 Efficacy 
• 
ORR, defined as the proportion of participants who have a BOR of confirmed CR or PR as 
determined by the Investigator using INRC. 
• 
DOR, defined as the time from first documentation of confirmed response (CR or PR) until the 
time of first documented PD by INRC based on Investigator assessment or death (whichever 
occurs first). 
• 
DCR, defined as the proportion of participants who have achieved a BOR of confirmed CR, 
confirmed PR, or stable disease by INRC based on Investigator assessment. 
• 
PFS, defined as the time from the date of the first dose of study treatment to the first 
documented PD, as determined by INRC based on Investigator assessment, or death from any 
cause (whichever occurs first). 
The criteria for evaluation of safety, PK, palatability of niraparib, and antidrug antibodies of 
dostarlimab are described in the master protocol. 
Statistical Methods: 
Sample Size Consideration 
Part 2 Safety Run-in  
The statistical gating to initiate the Part 2 Cohort Expansion will be based on minimum of 8 DLT-
evaluable participants for DLTs across osteosarcoma and neuroblastoma. When 2 or less DLTs and 2 
or less Grade ≥3 thrombocytopenia AEs are observed, the study will continue to Part 2 Cohort 
Expansion. When 3 or more DLTs are observed, the study may not continue to Part 2 Cohort 
Expansion. When 2 or less DLTs and 3 out of 8 Grade ≥3 thrombocytopenia AEs are observed, the 
study may be paused for data review. If there is a differential in the DLT-evaluable number of 
participants to 8 for either endpoint, other criteria may apply and will be specified in the SAP. This 
will be the primary guideline for the dose recommendations, the totality of data will be taken into 
account. The probability of initiating Part 2 Cohort Expansion and the probability of pausing for data 
review are presented in Section 9.1 for 8 DLT-evaluable participants, assuming a weak correlation of 
0.15 between the 2 endpoints. 
Part 2 Cohort Expansion 
The sample size for this cohort is based on a Simon’s 2-stage optimal design, with a 1-sided alpha of 
0.05 and a minimum power of 80%. The null hypothesis is ≤10% ORR, and the alternative hypothesis 
is ≥30% ORR. A futility analysis will be performed after the initial assessment of response for 
10 evaluable participants in the cohort. If, among the 10 mITT participants in the cohort, at least 2 
participants have objective responses (CR or PR), an additional 19 mITT participants will be enrolled. 
If 6 or more participants out of the 29 participants enrolled have objective responses, the null 
hypothesis will be rejected. The required sample size of 29 is based on the modified Intent-to-Treat 
(mITT) Population. The total sample size to be enrolled is planned at approximately 30 in case of the 
potential lack of sufficient participants in the mITT Population. For consideration of futility, those Part 
1 participants who satisfy the inclusion and exclusion criteria of Part 2, satisfy the mITT Population 
definition, and are treated at the dose used in Part 2 will be included in the Part 2 Cohort Expansion 
efficacy analysis and will be counted in the required Part 2 Cohort Expansion sample size. Under 
Protocol Amendment 05, neuroblastoma Safety Run-in participants who satisfy the mITT Population 
definition and are treated at the dose used in the Part 2 Cohort Expansion will also be included in the 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 17 of 75 
Part 2 Cohort Expansion efficacy analysis and will be counted in the required Part 2 Cohort Expansion 
sample size. The software for the sample size calculation is PASS 2019 (NCSS). 
Analysis Populations 
• 
The DLT-evaluable Population consists of participants in Part 2 Safety Run-in who complete 
the DLT observation period through at least 2 cycles of study treatment (including ≥80% of the 
intended niraparib dose and ≥2 infusions of dostarlimab) or experience a DLT for DLT 
endpoint (or Grade ≥3 thrombocytopenia AEs for the thrombocytopenia event endpoint).  
• 
The Safety Population is defined as all participants who receive at least 1 dose of either 
niraparib or dostarlimab. 
• 
The Intent-to-Treat Population includes all participants who receive any study medication and 
have measurable baseline tumour assessment and/or MIBG-positive disease (or FDG-positive 
disease, for MIBG-nonavid tumours) at baseline. 
• 
The mITT Population includes all participants who receive any study medication, have 
measurable baseline tumour assessment and/or MIBG-positive disease (or FDG-positive 
disease, for MIBG-nonavid tumours) at baseline, and have at least 1 postbaseline tumour 
assessment. 
• 
The Per-Protocol Population includes all participants in the mITT population who do not have 
protocol violations during the study that may significantly impact the interpretation of efficacy 
results. 
• 
The PK Population includes all participants who receive at least one dose of study treatment 
and have at least one PK sample. PK populations are defined separately for each agent. 
• 
Immunogenicity (ADA) Population includes all participants who receive at least 1 dose of 
dostarlimab and who have at least 1 ADA sample with a result. 
General Methods 
An overall description of the statistics for this study is provided in the master protocol. Additional 
details are provided in the Statistical Analysis Plan. 
Efficacy Analysis 
All analyses will include summary statistics, including number of participants and percentage for 
categorical variables and number of participants, mean, standard deviation, median, minimum, and 
maximum for continuous variables. Two-sided exact 95% Cis based on the Clopper-Pearson method 
will be provided where appropriate (Clopper, 1934). Time-to-event analyses will be performed using 
Kaplan-Meier methods. 
The primary analysis set for the efficacy endpoints will be the mITT Population. 
The number and proportion of participants with an objective response will be tabulated. ORR and DCR 
will be calculated, along with their estimated 2-sided 95% CI. Among the participants with a 
confirmed response, a time-to-event analysis of DOR will be performed using Kaplan-Meier methods, 
including quartile estimates and 2-sided 95% CI. PFS and its 2-sided 95% CI will be estimated using 
the Kaplan-Meier method. 
 
 
 
 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 18 of 75 
 
 
Safety, PK, Immunogenicity, and 
 
These analyses are described in the master protocol. 
1.2. 
Schemas 
Refer to the master protocol for the overall study schema.  
Figure 1: 
Part 2 Study Schema 
 
Abbreviations: CR=complete response; PFS6=PFS at 6 months; PR=partial response. 
1.3. 
Schedule of Activities (SoA) 
The schedule of activities (SoA) for this cohort is provided in Table 3. The tumour assessment 
flowchart is presented in Table 4.The study will be conducted in conformance with the protocol, 
Good Clinical Practice (GCP), and applicable regulatory requirements. Regulatory, ethical, and 
study oversight considerations are provided in Appendix 1 of the master protocol. 
 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 19 of 75 
Table 3: 
Schedule of Activities 
Protocol Activity 
Screening 
Period 
Treatment Period 
EOT Visit 
a,b 
Safety FUP 
Visit 
(30 [+7] Days 
Post-
Treatment)b 
FUP Assessment 
Period 
(Every 90 [±14] 
Days Post-
Treatment) c 
Study treatment cycle 
 
Cycles 1-2 
Cycles 3+ 
 
 
 
Cycle week 
 
1 
2 
3 
1 
2 
 
 
 
Study day 
-28 to -1 
 
 
 
 
 
 
 
 
Study visit window 
(days within cycle) 
 
±3 
±3 
±3 
±3 
±3 
+7 
+7 
±14 
Procedure 
 
 
 
 
 
 
 
 
 
Informed consent/assentd 
X 
 
 
 
 
 
 
 
 
Demographics and 
medical history 
X 
 
 
 
 
 
 
 
 
Performance status 
X 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
X 
 
 
 
 
 
 
 
 
Physical examination 
X 
A complete physical examination is to be conducted at Screening and EOT only, and as 
clinically indicated. 
 
 
Psychological 
assessments f 
X 
 
 
 
 
 
X 
 
 
Vital signs, weight, and 
height g 
X 
X 
X 
X 
X 
X (Cycle 3 
only) 
X 
X 
X 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 20 of 75 
Protocol Activity 
Screening 
Period 
Treatment Period 
EOT Visit 
a,b 
Safety FUP 
Visit 
(30 [+7] Days 
Post-
Treatment)b 
FUP Assessment 
Period 
(Every 90 [±14] 
Days Post-
Treatment) c 
Study treatment cycle 
 
Cycles 1-2 
Cycles 3+ 
 
 
 
Cycle week 
 
1 
2 
3 
1 
2 
 
 
 
Study day 
-28 to -1 
 
 
 
 
 
 
 
 
Study visit window 
(days within cycle) 
 
±3 
±3 
±3 
±3 
±3 
+7 
+7 
±14 
Procedure 
 
 
 
 
 
 
 
 
 
CBC with differential h 
X 
X  
(Twice 
weekly for 
Safety Run-
in only) 
X  
(Twice 
weekly for 
Safety Run-
in only) 
X  
(Twice 
weekly for 
Safety Run-
in only) 
X 
 
X 
 
 
Coagulation h 
X 
As clinically indicated 
X 
 
 
Blood chemistry h 
X 
X 
X 
X 
X 
 
X 
 
 
Serum or urine 
pregnancy test (WOCBP 
only) i  
X 
X 
 
 
X 
 
X 
X 
X 
12-lead ECG k 
X 
 
 
 
X (Cycle 3 
only) 
 
X 
 
 
Dostarlimab 
administration 
 
X 
 
 
X 
 
 
 
 
Niraparib 
dispensed/collected 
(administered Day 1 
after dostarlimab 
infusion) 
 
X 
 
 
X 
 
X 
(Collection 
only) 
 
 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 21 of 75 
Protocol Activity 
Screening 
Period 
Treatment Period 
EOT Visit 
a,b 
Safety FUP 
Visit 
(30 [+7] Days 
Post-
Treatment)b 
FUP Assessment 
Period 
(Every 90 [±14] 
Days Post-
Treatment) c 
Study treatment cycle 
 
Cycles 1-2 
Cycles 3+ 
 
 
 
Cycle week 
 
1 
2 
3 
1 
2 
 
 
 
Study day 
-28 to -1 
 
 
 
 
 
 
 
 
Study visit window 
(days within cycle) 
 
±3 
±3 
±3 
±3 
±3 
+7 
+7 
±14 
Procedure 
 
 
 
 
 
 
 
 
 
Tumour assessment: 
CT or MRIl,m 
Xn,o 
Every 9 weeks (every 63 [±7] days) following the start of study treatment 
for the first 12 months and then every 12 weeks (every 84 [±7] days) 
thereafter, or more frequently if clinically indicated, until documented PD, 
the start of alternative anticancer treatment, or discontinuation from overall 
study participation (e.g., death, participant’s request, or participant is lost to 
follow-up), whichever comes firstp 
Xq 
Tumour assessment: 
MIBG-SPECT/CT or 
FDG-PET/CT m 
Xn,o 
Every 9 weeks (every 63 [±7] days) following the start of study treatment 
for the first 12 months and then every 12 weeks (every 84 [±7] days) 
thereafter, or more frequently if clinically indicated, until documented PD, 
the start of alternative anticancer treatment, or discontinuation from overall 
study participation (e.g., death, participant’s request, or participant is lost to 
follow-up), whichever comes firstp 
Xq 
Bone marrow assessment 
Xs 
If positive at baseline, every 9 weeks (every 63 [±7] days) following the 
start of study treatment for the first 12 months and then every 12 weeks 
(every 84 [±7] days) thereafter, or more frequently if clinically indicated, 
until documented PD, the start of alternative anticancer treatment, or 
discontinuation from overall study participation (e.g., death, participant’s 
request, or participant is lost to follow-up), whichever comes first.  .  
Required for all participants to confirm disease response 
Xq 
AE monitoring u 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 22 of 75 
Protocol Activity 
Screening 
Period 
Treatment Period 
EOT Visit 
a,b 
Safety FUP 
Visit 
(30 [+7] Days 
Post-
Treatment)b 
FUP Assessment 
Period 
(Every 90 [±14] 
Days Post-
Treatment) c 
Study treatment cycle 
 
Cycles 1-2 
Cycles 3+ 
 
 
 
Cycle week 
 
1 
2 
3 
1 
2 
 
 
 
Study day 
-28 to -1 
 
 
 
 
 
 
 
 
Study visit window 
(days within cycle) 
 
±3 
±3 
±3 
±3 
±3 
+7 
+7 
±14 
Procedure 
 
 
 
 
 
 
 
 
 
Prior and concomitant 
medications and nondrug 
treatments 
X 
Medications and nondrug treatments will be monitored for study purposes from Screening to at least 30 days 
following the last dose of study treatment 
 
Blood sample for 
dostarlimab PK and/or 
ADAs and neutralising 
antibodies v,w 
 
X 
X (Cycle 1 
only) 
 
X (predose, 
Cycles 4 
and 6, and 
every 
6 cycles 
thereafter) 
 
X 
X 
X 
Blood sample for 
niraparib PK w,x 
 
X (Cycles 1 
and 2 only) 
X (Cycle 1 
only) 
 
 
 
 
 
 
Alternative anticancer 
treatment assessment 
 
 
 
 
 
 
X 
X 
X 
Abbreviations: ADA=antidrug antibody; AE=adverse event; AESI=adverse event of special interest; ALP=alkaline phosphatase; BP=blood pressure; 
; 
CBC=complete blood count; CNS=central nervous system; CR=complete response; CT=computed tomography; ECG=electrocardiogram; eCRF=electronic case report form; 
EOT=End of Treatment; FDG-PET/CT=fluorodeoxyglucose-positron emission tomography/computed tomography; FUP=follow-up; G-CSF=granulocyte-colony stimulating 
factor; HbcAb=hepatitis B core antibody; HbsAg=hepatitis B surface antigen; HCVAb=Hepatitis C virus antibody; INRC=International Neuroblastoma Response Criteria; 
IV=intravenous; MIBG-SPECT/CT=metaiodobenzylguanidine-single photon emission computed tomography/computed tomography; MRI=magnetic resonance imaging; 
PD=progressive disease; PET=positron emission tomography; PK=pharmacokinetics; PR=partial response; SAE=serious adverse event; WOCBP=woman of childbearing 
potential. 
a. 
All participants will undergo an EOT Visit no more than 7 days following the decision to discontinue study treatment for any reason. 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 23 of 75 
b. 
The Safety FUP Visit and EOT Visit can be combined if both fall within the same window. The Safety FUP Visit is to take place no sooner than 30 days after last dose to 
permit the protocol-required collection of AEs/SAEs occurring during this 30-day interval. The Safety FUP Visit has a window of +7 days. 
c. 
During the FUP Assessment Period, participants will be followed via clinic visit or telephone contact every 90 (±14) days after the last dose of study treatment for the first 
year, every 180 (±14) days for the subsequent 2 years, and yearly (±14 days) for an additional 2 years (5 years total), or until the start of alternative antitumour therapy 
(unless there is an ongoing AE/SAE that must be followed until resolved, stabilised, or otherwise explained), the participant withdraws from the study overall, is lost to follow-
up, or dies (whichever occurs earlier). 
d. 
Informed consent/assent must be obtained prior to undergoing any study-specific procedure and may occur prior to the 28-day Screening Period. 
e. 
 
 
 
f. 
Psychological assessments to be performed as per local standard of care. 
g. 
Vital signs include temperature, blood pressure, heart rate, and respiratory rate. Vital signs will be taken before, every 15 to 30 minutes during, and at the end of every 
dostarlimab infusion. Throughout the Treatment Period, all vital signs will be monitored at Week 1 of each cycle even if dostarlimab is not administered. In addition, for the 
first 8 weeks of the Treatment Period (up to and including Cycle 3 Week 2), all vital signs will be monitored at Week 2 and Week 3 of each cycle. Height and weight will be 
measured at Screening, Day 1 of each cycle, EOT, 30-day Safety Follow-up, and during the FUP Assessment Period. 
h. 
Haematology, coagulation, and chemistry assessments will be performed by local laboratories. Parameters required in this study are listed in the master protocol. 
Haematology and chemistry assessments must be measured within 7 days prior to Cycle 1 Day 1 to confirm eligibility. Haematology and chemistry must be performed, and 
results evaluated prior to study treatment administration. Haematology is to be checked twice each week during the first 2 cycles of study treatment for participants enrolled in 
the Part 2 Safety Run-in and once weekly for participants enrolled in the Part 2 Neuroblastoma Expansion Cohort. Haematology tests may be performed at a laboratory 
facility other than the study site, but the test results must be reported to the study site, the study site must keep a copy of test results with the participant’s study file, and the 
results must be entered into the eCRF. If dose interruption or modification is required at any point on study because of haematologic toxicity, weekly blood draws for CBC will 
be done according to Table 8. Additional haematology or chemistry assessments may be performed according to local standard of care or as clinically indicated. If Cycle 1 
Day 1 is no more than 7 days following sample collection for Screening, these samples do not need to be collected again for Cycle 1 Day 1, unless clinically warranted. 
Additional monitoring for haematology is to be performed after a niraparib dose increase due to a birthday or due to a weight increase that moves participants to a higher 
, respectively. Haematology is to be checked twice each week during the first 2 cycles after the niraparib dose increase for participants 
enrolled in the Part 2 Safety Run-in and once weekly for participants enrolled in the Part 2 Neuroblastoma Expansion Cohort. Blood samples should be collected in order of 
priority as outlined in Section 8.2.  
i. 
If the participant is a WOCBP, urine or serum pregnancy test will be performed by the local laboratory at the Screening Visit, within 24 hours prior to the first dose of study 
treatment, on Day 1 of every cycle for the duration of the Treatment Period, at the End of Treatment Visit, at the 30-day Safety Follow-up Visit, and 180 (±14) days after the 
last dose of study treatment. Pregnancy testing should occur irrespective of prior medical treatment. The results from these tests must be available and negative before study 
treatment is administered. Additional pregnancy testing may be necessary if required by local practices or regulations or if potential pregnancy is suspected. 
j. 
 
 
k. 
ECG should be repeated at Cycle 3 Week 1 and EOT, as well as during the Treatment or FUP Periods if clinically indicated. 
l. 
CT scans should be performed with contrast agents unless contraindicated for medical reasons. MRI of the abdomen and pelvis can be substituted for CT if MRI adequately 
depicts the disease. However, MRI of the chest should not be substituted for CT of chest even if IV contrast is contraindicated. In such a case, CT will be performed without 
contrast to evaluate the lung parenchyma. If MRI is used to follow-up bone lesion(s), it must be performed prior to any treatment that may affect bone marrow cellularity (eg, 
G-CSF). PET/CT may be used according to INRC guidelines with full-dose diagnostic CT and as clinically indicated. 
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 24 of 75 
m. The same imaging technique/modality must be used to follow identified lesions throughout the study for a given participant. Clinical assessment of superficial lesions should 
be carried out on the same date as the imaging studies or no later than 3 days thereafter and must be recorded in the participant’s eCRF. 
n. 
Participants must have a baseline tumour assessment (CT or MRI) of the chest, abdomen, pelvis, and any additional sites as clinically indicated within 28 days prior to the 
first dose of study treatment. Participants with neuroblastoma must also have a baseline tumour assessment via MIBG-SPECT/CT or FDG-PET/CT within 42 days prior to the 
first dose of study treatment. A baseline IV contrast-enhanced brain MRI (preferred) or IV contrast-enhanced CT scan (acceptable only if MRI contraindicated), is required for 
participants with previously treated brain metastases. Participants with previously treated brain metastases may participate under the conditions detailed in Exclusion 
Criterion 7. 
o. 
Radiologic assessments obtained per the standard of care prior to enrolment into the study do not need to be repeated and are acceptable to use as baseline evaluations, if 
all of the following conditions are met:  
(1) the CT or MRI tumour assessments were obtained within 28 days prior to the first dose of study treatment/the MIBG-SPECT/CT or FDG-PET/CT tumour 
assessments were obtained within 42 days prior to the first dose of study treatment  
(2) the assessments were performed using the method requirements outlined in INRC,  
(3) the same imaging technique/modality must be used to follow identified lesions throughout the study for a given participant, and  
(4) appropriate documentation indicating that these radiologic tumour assessments were performed as standard of care is available in the participant’s source notes. 
p. 
Tumour assessments of sites involved by disease at baseline, and of any additional sites as clinically indicated will be done postbaseline, as will MIBG-SPECT/CT or 
FDG-PET/CT tumour assessments (see Table 4). Tumour assessments will be conducted as per the schedule outline in Table 3. Tumour assessments should be scheduled 
using the date of the first dose of study treatment as the reference date for all time points and are not to be scheduled based on the date of the previous imaging time point. 
Imaging assessment delay to conform to study treatment delay is not permitted.  
q. 
Participants who have already demonstrated documented PD as per INRC do not need to have tumour assessments repeated at the EOT Visit or during the Post-Treatment 
FUP. Participants who do not have documented PD at time of study treatment discontinuation will continue to undergo tumour assessments on their original schedule (i.e., 
every 9 weeks [every 63 ±7 days] from the start of study treatment for the first 12 months and then every 12 weeks [every 84 ±7 days] thereafter, until documented PD, start 
of alternative anticancer treatment, or discontinuation from overall study participation [eg, death, participant’s request, or participant is lost to follow-up], whichever comes 
first). Participants who have a PR or CR while on treatment and discontinue treatment prior to the next disease assessment must have all appropriate follow-up disease 
assessments to confirm the observed response no sooner than 4 weeks (28 days) after the first observation. 
r. 
(Footnote intentionally left blank.) 
s. 
Bone marrow assessments obtained per the standard of care prior to enrolment into the study do not need to be repeated and are acceptable to use as baseline evaluations 
if obtained within 28 days prior to the first dose of study treatment. 
t. 
Only at Cycle 1 Week1 and Cycle 1 Week 2 for participants who receive 
 niraparib tablets and those who receive 
 
u. 
AEs will be collected until 30 days after the last dose of study treatment. SAEs will be collected until 90 days after the last dose of study treatment (or to a minimum of 
30 days after the last dose of study treatment if the participant starts alternative anticancer treatment). However, any SAEs assessed as related to study participation or 
related to study treatment will be recorded through the FUP Assessment Period. AESIs must be recorded on the eCRF. AESI collection periods are described in the master 
protocol. Any pregnancies that occur in female participants within 180 days after the last dose of study treatment or in partners of male participants within 90 days after the 
last dose of study treatment are to be reported as described in the master protocol. Pregnancies occurring more than 180 days after last dose of study treatment with an 
associated SAE (considered causally related to the study treatment by the Investigator) will follow the SAE reporting requirements. All AEs and SAEs will be followed, 
regardless of start of alternative anticancer therapy, until the event is resolved, stabilised, or otherwise explained; or until the participant has withdrawn consent to the study 
overall, is lost to follow-up (as defined in Section 7); or has died. 
v. 
Blood samples (single sample for all analytes) for serum dostarlimab PK and/or ADA and neutralising antibodies (NAb) will be collected from participants during Cycle 1 at the 
following time points relative to the start of the dostarlimab infusion: Cycle 1 Day 1 at Predose (PK, ADA, and NAb) and 1±0.5 hours postdose (PK only), Cycle 1 Day 8 at 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 25 of 75 
168±12 hours postdose (PK, ADA and NAb), and predose on Cycle 2 Day 1 (predose sample must be collected within 12 hours prior to infusion) (PK, ADA and NAb). Blood 
samples for serum dostarlimab PK, ADA, and NAb will also be collected at the following time periods: Predose in Cycles 4 and 6, every 6 cycles thereafter up to 2 years, and 
the EOT Visit. In addition, blood samples for serum dostarlimab ADA and NAb will be collected at the Safety Follow-up Visit (30 days post-treatment) and at the first Follow-
up Visit (90 days post-treatment). PK, ADA, and NAb samples will be drawn at the same time points and in the same collection, except as noted. 
w. The maximum blood volume for each sample for PK, ADA, and NAb) and exploratory biomarker assessments is 0.8 mL/kg, and the maximum total blood volume allowed for 
PK, ADA, and NAb, and exploratory biomarker assessments is 1.8 mL/kg per 3-week treatment cycle. Blood samples should be collected in order of priority as outlined in 
Section 8.2. 
x. 
Blood samples for plasma niraparib and M1 metabolite concentration analyses (single sample for both analyses) will be collected from participants during Cycle 1 Day 1 at 
2.5 and 7 hours after the first dose of niraparib, predose on Cycle 1 Day 8, predose on Cycle 2 Day 1, and Cycle 2 Day 1 at 5 hours after niraparib dose. Additional niraparib 
PK sampling is to be performed after a niraparib dose increase due to a birthday or after a dose modification due to a weight increase or decrease. (These additional PK 
samples will be taken on Day 1 in the first cycle after the dose change at 2.5 and 7 hours postdose, predose on Day 1 of the second cycle after the dose change, and at 5 
hours after the niraparib dose on Day 1 of the second cycle after the dose change.) Note: Predose samples must be collected within 2 hours prior to dosing; Cycle 1 Day 1 
2.5 hour samples must be collected at the scheduled time ±0.5 hour and other samples must be collected at the scheduled time ±2 hours. 
y. 
 
 Blood samples should be collected in order 
of priority as outlined in Section 8.2. 
 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 26 of 75 
Table 4: 
Tumour Assessment Flowchart 
Tumour 
Assessment 
Screening 
Period 
Treatment 
Period 
Confirmation of 
Responsea 
Post-Treatment 
Follow-up 
CT or MRI of 
chest, abdomen, 
pelvis, and any 
additional sites as 
clinically indicated 
Required 
Required, 
including site of 
any other tumour 
lesions identified 
at baseline and of 
any additional 
sites as clinically 
indicated 
Required, 
including site of 
any other tumour 
lesions identified 
at baseline  
If PD has been 
documented: Not 
required 
If PD has not been 
documented: 
Required, 
including sites of 
any other tumour 
lesions identified 
at baseline  
Brain scan (IV 
contrast-enhanced 
MRI [preferred] or 
IV contrast-
enhanced CT scan) 
Required for 
participants with 
previously 
treated brain 
metastases 
Not required 
unless clinically 
indicated  
Required if 
baseline scan was 
positive 
Not required 
unless clinically 
indicated 
MIBG-SPECT/CT 
for participants 
with MIBG-avid 
tumours or FDG-
PET/CT as the 
alternative 
modality for 
participants whose 
tumours do not 
concentrate MIBG 
Required 
Required 
Required 
If PD has been 
documented: Not 
required 
If PD has not been 
documented: 
Required 
Clinical assessment 
of superficial 
lesions 
Required 
Required for sites 
of tumour lesions 
identified at 
baseline and any 
additional sites as 
clinically 
indicated 
Required for sites 
of tumour lesions 
identified at 
baseline  
Required for sites 
of tumour lesions 
identified at 
baseline, unless 
PD has been 
documented 
elsewhere 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 27 of 75 
Tumour 
Assessment 
Screening 
Period 
Treatment 
Period 
Confirmation of 
Responsea 
Post-Treatment 
Follow-up 
Bone marrow 
aspirate and biopsy 
Required 
Required for 
participants with 
bone marrow 
involvement at 
Screening 
Required for all 
participants 
If PD has been 
documented: Not 
required 
If PD has not been 
documented: 
Required for 
participants with 
bone marrow 
involvement at 
Screening 
Abbreviations: CT=computed tomography; EOT=End of Treatment; FDG-PET/CT=fluorodeoxyglucose-positron 
emission tomography/computed tomography; MIBG-SPECT/CT=metaiodobenzylguanidine-single photon emission 
computed tomography/computed tomography; MRI=magnetic resonance imaging; PD=progressive disease.  
Note: See Table 3 for detailed guidance on tumour assessment procedures.  
a. 
Participants who have a PR or CR while on treatment and discontinue treatment prior to the next disease assessment must 
have all appropriate follow-up disease assessments to confirm the observed response no sooner than 4 weeks (28 days) 
after the first observation. 
 
 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 28 of 75 
2. 
INTRODUCTION 
An introduction to the overall study is provided in the master protocol. The objective of the 
Part 2 Safety Run-in Cohort is to evaluate the safety, tolerability and preliminary efficacy of the 
 
The objective of the Expansion Cohort of participants with neuroblastoma (the “NB Cohort”) is 
to assess the antitumour activity of the combination of niraparib and dostarlimab, assessed 
primarily by objective response rate (ORR) using International Neuroblastoma Response Criteria 
(INRC) in paediatric participants. 
2.1. 
Background 
2.1.1. 
Background of Niraparib 
Overall clinical experience with niraparib is summarised in the master protocol. 
2.1.2. 
Background of Dostarlimab 
Overall clinical experience with dostarlimab is summarised in the master protocol. 
2.1.3. 
Rationale for Synergy Between PARP Inhibitors and Immune Checkpoint 
Inhibitors 
The rationale for synergy between poly(adenosine diphosphate-ribose) polymerase (PARP) 
inhibitors and immune checkpoint inhibitors is summarised in the master protocol. 
2.2. 
Rationale for Tumour Type 
 
 
 
 
 
2.3. 
Rationale for Current Study 
The rationale for the current study is provided in the master protocol.  
2.4. 
Benefit Risk Assessment 
The overall benefit risk assessment and dose justification is described in the master protocol. 
 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 29 of 75 
3. 
STUDY OBJECTIVES AND PURPOSE 
The cohort-specific objectives for this study are defined in Table 5 as follows: 
Table 5: 
Objectives and Endpoints for Study 213406 Neuroblastoma Cohort 
Objectives 
Endpoints 
Part 2 Safety Run-in 
Primary 
Assessment of safety and tolerability of the 
 
 by assessing DLT and Grade ≥3 
thrombocytopenia AEs in paediatric participants 
• 
Assess the incidence of DLTs in the Part 2 
Safety Run-in for the DLT-evaluable 
Population. 
• 
Assess the incidence of Grade ≥3 
thrombocytopenia AEs in the Part 2 Safety 
Run-in for the DLT-evaluable Population. 
Secondary 
Evaluation of measures of anticancer activity, 
including ORR, DOR, DCR, and PFS in 
paediatric participants 
ORR is defined as the proportion of participants 
who have a BOR of confirmed CR or PR as 
determined by the Investigator using INRC for 
participants with neuroblastoma or RECIST v1.1 
for participants with osteosarcoma. 
DOR is defined as the time from first 
documentation of confirmed response (CR or PR) 
until the time of first documented PD by INRC for 
participants with neuroblastoma or RECIST v1.1 
for participants with osteosarcoma based on 
Investigator assessment or death (whichever 
occurs first). 
DCR is defined as the proportion of participants 
who have achieved a BOR of confirmed CR, 
confirmed PR, or stable disease by INRC for 
participants with neuroblastoma or RECIST v1.1 
for participants with osteosarcoma based on 
Investigator assessment. 
PFS is defined as the time from the date of the 
first dose of study treatment to the first 
documented PD, as determined by INRC for 
participants with neuroblastoma or RECIST v1.1 
for participants with osteosarcoma based on 
Investigator assessment, or death from any cause 
(whichever occurs first). 
To evaluate safety of the combination of 
 
 in paediatric participants 
Assess the incidence of TEAEs, SAEs, imAEs, 
TEAEs leading to death, and AEs leading to 
treatment discontinuation. AE evaluation period is 
while participants are on treatment or up to 
90 days after the last dose of study treatment. 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 30 of 75 
Objectives 
Endpoints 
To characterise the PK of niraparib in paediatric 
participants 
Niraparib concentrations; PK parameters of 
niraparib, if appropriate. 
Part 2 Expansion 
Primary 
Assess the antitumour activity of the combination 
of 
, assessed primarily 
by ORR (using INRC) in paediatric participants 
ORR is defined as the proportion of participants 
who have a BOR of confirmed CR or PR as 
determined by the Investigator using INRC. 
Secondary 
Evaluation of additional measures of anticancer 
activity including DOR, DCR, and PFS in 
paediatric participants 
DOR is defined as the time from first 
documentation of confirmed response (CR or PR) 
until the time of first documented PD by INRC 
based on Investigator assessment or death 
(whichever occurs first).  
DCR is defined as the proportion of participants 
who have achieved a BOR of confirmed CR, 
confirmed PR, or stable disease by INRC based 
on Investigator assessment. 
PFS is defined as the time from the date of the 
first dose of study treatment to the first 
documented PD as determined by INRC based on 
Investigator assessment, or death from any cause 
(whichever occurs first). 
Evaluation of the safety of the combination of 
 in 
paediatric participants 
Assess the incidence of TEAEs, SAEs, imAEs, 
TEAEs leading to death, and AEs leading to 
treatment discontinuation. AE evaluation period is 
while participants are on treatment or up to 
90 days after the last dose of study treatment.  
Characterisation of the PK of the combination of 
niraparib and dostarlimab in paediatric 
participants 
Niraparib and dostarlimab concentrations; PK 
parameters of niraparib and dostarlimab, if 
appropriate. 
Assessment of the immunogenicity of dostarlimab 
in paediatric participants 
Rate and extent of ADAs to dostarlimab. 
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 31 of 75 
Objectives 
Endpoints 
Exploratory 
Abbreviations: ADA=antidrug antibody(ies); AE(s)=adverse event(s); BOR=best overall response; CR=complete 
response; 
; DCR=disease control rate, DLT=dose limiting toxicity; DOR=duration 
of response; INRC=International Neuroblastoma Response Criteria; imAE=immune-mediated adverse event; 
ORR=objective response rate; 
; PD=progressive disease; PD-
1=programmed cell death protein 1; PFS=progression-free survival; PK=pharmacokinetic(s); PR=partial response; 
RECIST=Response Evaluation Criteria in Solid Tumours; SAE(s)=serious adverse event(s); SoA=schedule of 
activities; TEAE(s)=treatment-emergent adverse event(s); 
. 
CCI
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 32 of 75 
4. 
INVESTIGATIONAL PLAN 
4.1. 
Overall Study Design 
The overall study design is described in the master protocol. 
The Part 2 study design is illustrated in Figure 1.  
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 33 of 75 
Once all participants in the Safety Run-in have been observed for ≥42 days, all available data 
from the Part 2 Safety Run-in together with all data previously collected under Protocol 
Amendment 04 and earlier, will be reviewed by the study DEC and Data Review Committee 
(DRC) before additional participants on Part 2 are enrolled.  
Following the Safety Run-in, if the 
 is deemed safe, up to 
30 evaluable participants may enrol in the Part 2 Cohort Expansion for neuroblastoma, inclusive 
of any eligible participants with neuroblastoma treated in the Part 2 Safety Run-in. Enrolment 
into the Part 2 Cohort Expansion will be conducted according to a Simon’s 2-stage optimal 
design in which ≥2 of the first 10 evaluable participants must experience an objective tumour 
response (as assessed by the Investigator using INRC) before accrual of the remaining 
20 participants.  
 
 
 
 
 
 
 
  
 
 
General study conduct is described in the master protocol. 
 
 
 
 
 
4.1.1. 
Dose Limiting Toxicity 
The DLT and thrombocytopenia toxicities observation period for the Safety Run-in is 42 days 
following the initiation of study treatment (i.e., approximately the first 2 treatment cycles) in 
Part 2.  
CCI
CCI
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 34 of 75 
A participant will be considered unevaluable for DLT assessment if, for reasons other than DLT, 
the participant does not complete the DLT observation period or receives <80% of the intended 
niraparib dose (e.g., missed 9 or more doses; reason for missed doses may include, but is not 
limited to, noncompliance) or <2 infusions of dostarlimab.  
A participant will be considered unevaluable for thrombocytopenia events if, for reasons other 
than thrombocytopenia, the participant does not complete the DLT observation period or 
receives <80% of the intended niraparib dose (e.g., missed 9 or more doses; reason for missed 
doses may include, but is not limited to, noncompliance) or <2 infusions of dostarlimab. 
Participants considered unevaluable may be replaced after consultation between the Sponsor and 
Investigator.  
A participant may continue on study treatment following a DLT or a thrombocytopenia event if 
the Investigator determines doing so is in the best interest of the participant, after discussion by 
the Investigator with the GSK Medical Monitor, and after appropriate recovery from the DLT by 
the participant. 
DLT is defined as any of the following occurring during the first 42 days of study treatment: 
• 
any treatment-related Grade 4 nonhaematologic clinical (nonlaboratory) AE 
• 
any treatment-related Grade 3 nonhaematologic clinical (nonlaboratory) AE not resolving 
to Grade ≤1 within 48 hours of initiating optimal medical intervention 
• 
any treatment-related Grade 3 or 4 nonhaematologic laboratory abnormality if any of the 
following also occur:  
− the abnormality leads to hospitalisation. 
− the abnormality persists for ≥7 days from the time of AE onset and participant is 
symptomatic from the AE and/or requires intervention. 
• 
any treatment-related haematologic toxicity defined as any of the following:  
− Grade 4 thrombocytopenia persists for >7 days from the time of AE onset or Grade 3 
or 4 thrombocytopenia associated with clinically significant bleeding or requiring 
platelet transfusion. 
− Grade 4 neutropenia persists for >7 days, Grade 3 or 4 neutropenia associated with 
infection, or Grade 3 or 4 febrile neutropenia persists for ≥72 hours. 
− Grade 4 anaemia or Grade 3 anaemia requiring blood transfusion. 
• 
any treatment-related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2 
• 
any treatment-related Grade ≥2 uveitis, eye pain, or blurred vision that does not resolve 
with topical therapy within 2 weeks 
• 
any treatment-related Grade ≥2 immune-related endocrine toxicity that requires hormone 
replacement, except Grade 2 thyroiditis or thyroid dysfunction 
• 
any treatment-related Grade 2 colitis or diarrhoea that persists for ≥7 days without 
resolution to Grade ≤1 despite adequate steroid therapy 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 35 of 75 
• 
any Grade 3 or 4 imAE that does not resolve to Grade ≤1 or baseline within 8 days despite 
adequate immune suppressive therapy 
• 
Grade 3 or higher infusion-related reaction 
• 
any grade of hemophagocytic lymphohistiocytosis 
• 
any grade of Posterior Reversible Encephalopathy Syndrome (PRES) 
• 
any treatment-related Grade 5 AE 
Thrombocytopenia events are defined as any of the following occurring during the first 42 days 
of study treatment: 
• 
any treatment-related toxicity defined as any of the following:  
− Grade 3 Grade 4 thrombocytopenia 
4.2. 
Number of Participants 
Safety Run-in: approximately 8 DLT-evaluable participants in total across osteosarcoma 
(Part 2A) and neuroblastoma (Part 2B). 
Part 2 Expansion: approximately 30 participants with neuroblastoma are planned for enrolment 
in this cohort (including eligible participants with neuroblastoma from the Safety Run-in). See 
Section 9.1 for eligibility requirements for enrolment of Safety Run-in participants in the Part 2 
Cohort Expansion. 
4.3. 
Treatment Assignment 
All participants enrolled in this cohort will receive niraparib in combination with dostarlimab as 
described in Section 4.1. 
4.4. 
Dose Adjustment Criteria 
4.4.1. 
Dose Adjustment Criteria for Age and Weight 
 
4.4.2. 
Dose Adjustment for Adverse Events 
Adverse reactions should be managed with dose reduction, interruption of treatment, or dose 
discontinuation. 
All dose reductions, treatment delays (including any missed doses) and discontinuations, and the 
reason for such modifications should be recorded in the eCRF. 
It should be noted that required treatment discontinuation of either niraparib or dostarlimab will 
result in study treatment discontinuation of both treatments. 
4.4.3. 
Niraparib 
The recommended dose modifications for adverse reactions should be followed as listed in 
Table 6, Table 7, and Table 8. Following a dose reduction, participants should not subsequently 
have dose re-escalated unless a discussion with the GSK Medical Monitor has occurred. 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 36 of 75 
Following 2 dose reductions, participants will not be allowed to further dose reduce, and study 
treatment should be discontinued. In addition, study treatment should be discontinued for 
selected AEs that persist beyond 28 days, as noted in Table 7 and Table 8. 
 
Table 7: 
Niraparib Dose Modifications for Nonhaematologic Adverse Reactions 
NCI CTCAE Grade ≥3 adverse reaction 
where prophylaxis is not considered 
feasible or adverse reaction event persists 
despite treatment 
• Withhold niraparib for a maximum of 28 days or until 
resolution of adverse reaction. 
• For those adverse reactions that do not resolve within 
28 days, niraparib should be discontinued. Otherwise, 
discussion with the GSK Medical Monitor is required 
to resume niraparib. 
• Resume niraparib at a reduced dose per Table 6. 
NCI CTCAE Grade ≥2 adverse reaction of 
PRES 
• 
Discontinue study treatment for participants 
Abbreviations: CTCAE=Common Terminology Criteria for Adverse Events; NCI=National Cancer Institute; 
PRES=Posterior Reversible Encephalopathy Syndrome. 
There have been rare reports of niraparib-treated patients developing signs and symptoms that 
are consistent with PRES. PRES is a rare neurologic disorder that can present with signs and 
symptoms including seizures, headache, altered mental status, visual disturbance, or cortical 
blindness, with or without associated hypertension. A diagnosis of PRES requires confirmation 
by brain imaging, preferably magnetic resonance imaging. In patients developing PRES, 
treatment of specific symptoms including control of hypertension is recommended, along with 
discontinuation of niraparib. The safety of reinitiating niraparib therapy in patients previously 
experiencing PRES is not known.  
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 37 of 75 
Table 8: 
Niraparib Dose Modifications for Haematologic Adverse Reactions 
Weekly blood draws for CBC will be monitored until the adverse reaction resolves; after resuming 
niraparib, weekly blood draws for CBC will be required for an additional 4 weeks (28 days) after the 
adverse reaction has been resolved to the specified levels, after which monitoring at Week 1 of each 
cycle may resume (Table 3). 
Platelet count <100 000/µL 
First occurrence: 
• Withhold niraparib for a maximum of 28 days and monitor blood 
counts weekly until platelet counts return to ≥100 000/µL. Resume 
niraparib at the same or lower dose per Table 6. 
• For those adverse reactions that do not resolve within 28 days, study 
treatment should be discontinued. Otherwise, discussion with the 
GSK Medical Monitor is required to resume niraparib. 
• Resume niraparib at the same or reduced dose per Table 6. 
• If nadir platelet count was <75 000/µL, niraparib dose should be 
reduced per Table 6. 
Second occurrence: 
• Withhold niraparib for a maximum of 28 days and monitor blood 
counts weekly until platelet counts return to ≥100 000/µL. 
• For those adverse reactions that do not resolve within 28 days, study 
treatment should be discontinued. Otherwise, discussion with the 
GSK Medical Monitor is required to resume niraparib.  
• Resume niraparib at a reduced dose per Table 6 
Neutrophil <1000/µL or  
Haemoglobin <8 g/dL 
• Withhold niraparib for a maximum of 28 days and monitor blood 
counts weekly until neutrophil counts return to ≥1000 µL or 
haemoglobin returns to ≥8 g/dL. 
• For those adverse reactions that do not resolve within 28 days, study 
treatment should be discontinued. Otherwise, discussion with the 
GSK Medical Monitor is required to resume niraparib. 
• Resume niraparib at a reduced dose per Table 6 
Haematologic adverse 
reaction requiring 
transfusion 
• For participants with platelet count ≤10 000/μL, platelet transfusion 
should be considered. If there are other risk factors, such as 
co-administration of anticoagulation or antiplatelet drugs, consider 
interrupting these drugs and/or transfusion at a higher platelet count. 
• Red blood cell transfusion(s) may be given at the discretion of the 
Investigator. 
• Resume niraparib at a reduced dose per Table 6. 
MDS/AML 
Any suspected case of MDS/AML reported while a participant is 
receiving treatment or followed for post-treatment assessments must be 
referred for evaluation to a local haematologist to perform bone marrow 
aspirate and biopsy as per local standards of practice. The study site 
must receive a copy of the haematologist’s report of aspirate/biopsy 
findings, which must include a classification according to the WHO, and 
other sample testing reports related to MDS/AML. If a diagnosis of 
MDS/AML is confirmed by a haematologist, the participant must 
permanently discontinue study treatment. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 38 of 75 
For clinical situations not covered by this dose modification guidance, the Investigator must 
contact the GSK Medical Monitor. 
4.4.4. 
Dostarlimab 
Dostarlimab dose adjustment criteria are presented in the master protocol. 
4.5. 
Criteria for Study Termination  
Criteria for study termination are described in the master protocol. 
4.6. 
End of Study Definition 
End of study definition is described in the master protocol. 
4.7. 
Study Conduct 
4.7.1. 
Procedures by Visit 
Standard of care tests/procedures, including laboratory assessments, ECG, physical examination, 
vital signs, height, weight, and performance status, performed before the enrolment into the 
study can be used as part of the Screening assessments as long as the tests/procedures are 
performed within the visit window indicated in Table 3. Local laboratory assessments 
(chemistry, haematology) must be performed and results reviewed no more than 7 days prior to 
administration of the first dose of study treatment, as indicated in Table 3. Tumour assessment 
CT or MRI, and MIBG-SPECT/CT or FDG-PET/CT scan obtained per the standard of care prior 
to the first dose of study treatment (within 28 days for CT or MRI and 42 days for 
MIBG-SPECT/CT or FDG-PET/CT) do not need to be repeated and are acceptable to use as 
baseline evaluations if the conditions presented in Section 8.1.2.1 of the master protocol are met. 
Source documents must clearly identify the standard of care tests/procedures that are used for 
Screening, and the results of these tests/procedures must be entered in the eCRF. Table 3 details 
which procedures are performed at each visit. 
4.7.2. 
General Guidance for Treatment Continuity when Participants are Unable to 
Come into the Clinic  
Due to the significant challenges that currently face the healthcare system and patients due to 
Coronavirus Disease 2019 (COVID-19), as well as the potential for enduring or additional 
quarantine measures, the following guidance is being provided in this protocol. In the spirit of 
global diversity in the COVID-19 pandemic and its impact on healthcare in each individual 
country as well as the recently issued guidance by several regulatory authorities, the autonomy of 
each investigative site to assess the benefit/risk for their patients participating in clinical studies 
should be maintained. 
Prior to utilisation of any of the measures outlined in this section, discussion and approval must 
be obtained from Sponsor/contract research organisation.  
It is expected that sites participating in clinical studies will make every effort to ensure proper 
monitoring and well-being of enrolled participants by adhering to safety monitoring as outlined 
in the SoA (Table 3). The use of local laboratories and local radiology centres to reduce the need 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 39 of 75 
for a participant to come into the clinic are supported, if deemed necessary for the well-being of 
the participant. These local facilities should be added to regulatory documents, as required. 
Additionally, regulatory guidance issued in response to the COVID-19 pandemic supports the 
use of central and remote monitoring programs to maintain oversight of clinical sites. Any 
restrictions in place at the site that will impact monitoring and/or participant access to the site 
and care providers should be communicated to the Sponsor/contract research organisation.  
General rules for participants with limited possibility to travel are as follows: 
• If possible, replace in-person visits with phone contact or alternative location for 
assessment (eg, local laboratories and imaging centres). 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 40 of 75 
5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrolment criteria, also known as 
protocol waivers or exemptions, are not permitted. 
5.1. 
Participant Inclusion Criteria 
Participants will be eligible for the Safety Run-in and Neuroblastoma Expansion Cohort of Part 2 
if all of the following criteria are met: 
1. 
 
 
. 
2. Participant with neuroblastoma has measurable/evaluable disease by International 
Neuroblastoma Response Criteria (INRC) at screening. Participants with 
recurrent/relapsed bone metastasis that is metaiodobenzylguanidine (MIBG)-positive (or 
FDG-positive, for MIBG-nonavid tumours) as only site of disease are eligible. 
5. Performance status must be ≥60% on the Karnofsky scale for participants >16 years of 
age and ≥60% on the Lansky scale for participants ≤16 years of age. 
Note: Neurologic deficits in participants with brain metastases must have been stable for 
at least 7 days prior to study enrolment. Participants who are unable to walk because of 
paralysis, but who are upright in a wheelchair, will be considered ambulatory for the 
purpose of assessing the performance status. 
6. Participant has adequate organ function, defined as follows: 
Note: The participant must not have received blood transfusion, growth factors, or 
platelet stimulating agents in the 14 days prior to providing a sample for haematologic 
analysis nor erythropoietin in the prior 6 weeks. 
a. absolute neutrophil count ≥1000/μL 
b. platelets ≥100 000/μL 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 41 of 75 
c. haemoglobin ≥8 g/dL or ≥5.0 mmol/L 
d. creatinine≤1.5×upper limit of normal (ULN) for age or calculated creatinine 
clearance or radioisotope glomerular filtration rate ≥60 mL/min/1.73m2 
e. total bilirubin ≤1.5 × ULN or direct bilirubin ≤1 × ULN 
f. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN 
unless liver metastases are present, in which case AST and ALT must be ≤5 × ULN 
g. international normalised ratio or prothrombin time (PT) ≤1.5 × ULN unless the 
participant is receiving anticoagulant therapy, as long as PT or partial thromboplastin 
time (PTT) is within therapeutic range of intended use of anticoagulants 
h. activated PTT ≤1.5 × ULN unless the participant is receiving anticoagulant therapy, 
as long as PT or PTT is within therapeutic range of intended use of anticoagulants 
7. A female participant is eligible to participate if she is not pregnant or breastfeeding, and 
at least one of the following conditions applies: 
a. Is not a woman of childbearing potential (WOCBP). 
Or 
b. 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 3 of the master protocol, from the Screening Visit through at least 180 days 
after the last dose of study treatment and agrees not to donate eggs (ova, oocytes) for 
the purpose of reproduction during this period. The Investigator should evaluate the 
effectiveness of the contraceptive method in relationship to the first dose of study 
treatment. 
c. A WOCBP must have a negative highly sensitive pregnancy test (urine or serum, as 
required by local regulations) within 24 hours prior to the first dose of study treatment 
and irrespective of prior medical treatment. 
Additional requirements for pregnancy testing during and after the Treatment Period are 
located in the master protocol. 
The Investigator is responsible for review of medical history, menstrual history, and 
recent sexual activity to decrease the risk for inclusion of a woman with an early 
undetected pregnancy. 
8. A male participant of reproductive potential is eligible to participate if he agrees to the 
following starting with the first dose of study treatment through at least 90 days (a 
spermatogenesis cycle) after the last dose of study treatment: 
a. refrain from donating sperm 
plus, either: 
b. be abstinent from heterosexual intercourse as their preferred and usual lifestyle 
(abstinent on a long-term and persistent basis) and agree to remain abstinent 
or 
c. must agree to use a male condom and should also be advised of the benefit for a 
female partner to use a highly effective method of contraception, as a condom may 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 42 of 75 
break or leak, when having sexual intercourse with a WOCBP who is not currently 
pregnant 
9. The Investigator, or a person designated by the Investigator, will obtain written informed 
consent from each study participant or the participant’s legally acceptable representative, 
parent(s), or legal guardian and the participant’s assent, when applicable, before any 
study-specific activity is performed. The Investigator will retain the original copy of each 
participant’s signed consent/assent document. 
10. 
 
 
 
 
 
 
 
 
 
 
5.2. 
Participant Exclusion Criteria 
Participants will not be eligible for study entry if any of the following criteria are met: 
1. Participation presents unacceptable risk to the prospective participant based on the 
Investigator’s judgement. 
2. Participant has known hypersensitivity to dostarlimab or niraparib, their components, or 
their excipients. 
3. Participant has received prior therapy with an anti-PD-1, anti-programmed cell death-
ligand 1, anti-programmed cell death-ligand 2, anticytotoxic T-lymphocyte-associated 
antigen-4 antibody (including ipilimumab), or any other antibody or drug specifically 
targeting T-cell co-stimulation or checkpoint pathways (with the exception of participants 
rolling over from Part 1 of the study: these participants are allowed to have received 
dostarlimab). 
4. Participant has had prior treatment with a known PARP inhibitor (with the exception of 
participants rolling over from Part 1 of the study: these participants are allowed to have 
received niraparib). 
5. Participant has a known history of myelodysplastic syndrome or acute myeloid 
leukaemia. 
6. Participant has active autoimmune disease that has required systemic treatment in the past 
2 years (i.e., with use of disease-modifying antirheumatic drugs, corticosteroids, or 
immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic 
corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not 
considered a form of systemic treatment. 
7. Participant has known active central nervous system (CNS) metastases, carcinomatous 
meningitis, or both. Note: Participants with previously treated brain metastases may 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 43 of 75 
participate provided they are clinically stable and have no evidence of new, enlarging, or 
progressing brain metastases (using the identical imaging modality for each assessment, 
either MRI or CT scan) for at least 4 weeks (28 days) prior to the first dose of study 
treatment. In addition, the participant must not have been using steroids for at least 7 days 
prior to the first dose of study treatment. Carcinomatous meningitis precludes a 
participant from study participation regardless of clinical stability. 
8. Participant had a known additional (second primary) malignancy that progressed or 
required active treatment within the last 2 years. 
9. Participant is considered a poor medical risk due to a serious, uncontrolled medical 
disorder, nonmalignant systemic disease, or active infection that requires systemic 
therapy. Specific examples include, but are not limited to, history of (noninfectious) 
pneumonitis that required steroids or current pneumonitis, uncontrolled ventricular 
arrhythmia, uncontrolled major seizure disorder, unstable spinal cord compression, 
superior vena cava syndrome, or any psychiatric or substance abuse disorders that would 
interfere with cooperation with the requirements of the study (including obtaining 
assent/consent). 
10. Participant has a condition (such as transfusion-dependent anaemia or 
thrombocytopenia), requirement for therapy, or laboratory abnormality that might 
confound the study results or interfere with the participant’s participation for the full 
duration of the study treatment. 
11. Participant is pregnant, breastfeeding, or expecting to conceive within the projected 
duration of the study, starting with the Screening Visit through 180 days after the last 
dose of study treatment. 
No data are available regarding the presence of dostarlimab or niraparib or its metabolites 
in human milk, or on its effects on the breastfed infant or milk production. Because of the 
potential for serious adverse reactions in breastfed infants from dostarlimab and/or 
niraparib, female participants should not breastfeed during treatment with dostarlimab 
and/or niraparib and for at least 4 months after the last dose of dostarlimab or at least 
30 days after the last dose of niraparib, whichever is longer. 
12. Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy 
or any other form of immunosuppressive therapy within 7 days prior to the first dose of 
study treatment. 
13. Participant has a known history of HIV (type 1 or 2 antibodies). 
14. Participant has documented presence of HbsAg and/or HbcAb at Screening or within 
3 months prior to first dose of study intervention. Participants with a negative HbsAg and 
positive HbcAb result are eligible only if HBV DNA is negative (Appendix 12 of the 
master protocol), 
15.  Participant must not have a gastrointestinal condition, such as bowel obstruction, that 
can impact absorption of oral medications and is identified by clinical symptoms or CT 
scan, etc. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 44 of 75 
16. Participant has had any known Grade 3 or 4 anaemia, neutropenia, and/or 
thrombocytopenia that was related to the most recent prior anticancer therapy and that 
persisted >4 weeks (28 days). 
17. Participant has not recovered (ie, to Grade ≤1 or to baseline) from prior systemic therapy-
induced AEs. Note: Participants with alopecia, hearing impairment, Grade ≤2 
neuropathy, Grade ≤2 fatigue, Grade ≤2 anaemia, and/or Grade ≤2 neutropenia are an 
exception to this criterion and may qualify for participation in the study. 
18. Participant had toxicity related to prior immunotherapy that led to treatment 
discontinuation. 
19. Participant had treatment with systemic anticancer therapy (investigational agent or 
device, or approved chemotherapy, targeted therapy, immunotherapy, or other systemic 
therapy) within the 3 weeks or 5 half-lives, whichever is shorter prior to the first dose of 
study treatment, radiation therapy encompassing >20% of the bone marrow within 
2 weeks prior to the first dose of study treatment, or any radiation therapy within 1 week 
prior to the first dose of study treatment. 
20. Participant has not recovered adequately from AEs or complications from any major 
surgery prior to starting study treatment. 
21. Participant has received a live vaccine within 30 days of planned start of study treatment. 
22. Participant has clinically significant cardiovascular disease (eg, significant cardiac 
conduction abnormalities, uncontrolled hypertension, cardiac arrhythmia or unstable 
angina, New York Heart Association Grade 2 or greater congestive heart failure, serious 
cardiac arrhythmia requiring medication, and history of cerebrovascular accident) within 
6 months of enrolment. 
23. Participant has heart rate-corrected QT interval prolongation at Screening >450 msec or 
>480 msec for participants with bundle branch block. 
Notes: 
• The QTc is the QT interval corrected for heart rate according to Bazett’s formula 
(QTcB), Fridericia’s formula (QTcF), and/or another method, machine read or 
manually over read. 
• The specific formula that will be used to determine eligibility and discontinuation 
for an individual participant must be determined prior to initiation of the study 
and used consistently for eligibility and study assessments.  
24. Participant has received a solid organ transplant. 
25. Participant has a documented presence of HCV antibody at Screening or within 3 months 
prior to first dose of study intervention. NOTE: Participants with a positive HCV 
antibody test result due to prior resolved disease can be enrolled, only if a confirmatory 
HCV RNA test is negative and the participant otherwise meets all entry criteria. 
26. Participant has a documented presence of HCV RNA at Screening or within 3 months 
prior to first dose of study intervention. NOTE: The HCV RNA test is optional and 
participants with negative HCV antibody test are not required to undergo HCV RNA 
testing as well. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 45 of 75 
5.3. 
Lifestyle Considerations 
Cases of photosensitivity have been reported for patients on niraparib treatment. Participants 
must be informed on measures to decrease exposure to ultraviolet light, such as minimising time 
in direct sunlight unless wearing hats and long-sleeves and application of sun protection creams. 
5.4. 
Screen Failures 
The definition of a screen failure is provided in the master protocol. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 46 of 75 
6. 
STUDY TREATMENT(S) AND CONCOMITANT THERAPY 
6.1. 
Study Treatment(s) Administered 
 
Niraparib will be dispensed to participants on Day 1 of every 21-day treatment cycle. 
The niraparib dosing regimens under Protocol Amendment 05 are shown the master protocol.  
 
 
Details about the investigational products are provided in Table 9. 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 47 of 75 
Table 9: 
Investigational Products 
 
Investigational Product 
Intervention name Niraparib 
Niraparib 
Dostarlimab 
Type 
Drug  
Drug 
Biologic 
Dosage form 
Unit dose 
Route of 
administration 
Use 
IMP 
IMP 
IMP 
Authorised 
AxMP/ 
Unauthorised 
AxMP 
Not applicable 
Not applicable 
Not applicable 
Sourcing 
Provided centrally by the 
Sponsor  
Provided centrally by the 
Sponsor  
Provided centrally by the 
Sponsor  
Physical 
description 
(Packaging and 
Labelling; see 
Section 6.2.1) 
Dose level(s) 
See master protocol 
See master protocol 
See master protocol 
Manufacturer 
WuXi STA (WuXi), 
China (DS, DP) 
Dishman, India (DS) 
Corden, Colorado, US 
(DS) 
Mayne Pharma, Raleigh, 
North Carolina, US (DP) 
Siegfried, Switzerland 
(DS) 
WuXi STA (WuXi), 
China (DS, DP) 
Corden, Colorado, US 
(DS) 
Dishman, India (DS) 
Siegfried, Switzerland 
(DS) 
WuXi Biologics (WuXi), 
Wuxi, China (DS) 
Ajinomoto Althea (Aji), 
San Diego, California, 
US (DP) 
Abbreviations: AxMP = auxiliary medicinal product; DP=drug product; DS=drug substance; IMP = investigational 
medicinal product; IV=intravenous; Non-IMP = non-investigational medicinal product; 
 
; US=United States. 
Further details on the study interventions are provided in the master protocol and respective IBs. 
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 48 of 75 
6.2. 
Preparation/Handling/Storage/Accountability 
6.2.1. 
Study Treatment Packaging and Labelling 
Overall study treatment packaging and labelling are described in the master protocol. 
6.2.2. 
Study Treatment Storage 
Study treatment storage is described in the master protocol. 
6.2.3. 
Administration 
Details on the administration of the study treatments can be found in the Pharmacy Manual. A 
summary is provided in the master protocol. 
6.2.4. 
Study Treatment Accountability 
Study treatment accountability is described in the master protocol. 
6.2.5. 
Study Treatment Handling and Disposal 
Study treatment handling and disposal are described in the master protocol. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
This is a non-randomised, open-label study. 
6.4. 
Study Treatment Compliance 
Overall study treatment compliance information is presented in the master protocol. Study 
treatment (dostarlimab and niraparib during dostarlimab infusion visits) will be administered by 
investigational site personnel at investigational sites. 
6.5. 
Dose Modification 
Dose reductions for dostarlimab are not permitted while participant is being treated on study. 
Dosing may be held in the event of an AE which may be deemed related to treatment. If 2 or 
more consecutive dostarlimab doses are held, Investigator must notify the GSK Medical Monitor 
for approval to continue treatment of the participant on study. 
Refer to Section 4.4 for full dose modification guidance for niraparib and Section 4.7 in the 
master protocol for full dose modification guidelines for dostarlimab.  
6.6. 
Treatment of Overdose 
This information is described in the master protocol.  
6.7. 
Concomitant Therapy 
Details on the definition and recording of concomitant medications are provided in the master 
protocol. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 49 of 75 
6.7.1. 
Rescue Medications 
Participants should receive appropriate supportive care measures as deemed necessary by the 
treating Investigator, including but not limited to the items outlined in Section 6.8.1 of the master 
protocol.  
6.7.2. 
Prohibited Medications 
Known prior medications that exclude a participant from participating in this cohort are 
described in the exclusion criteria (see Section 5.2). 
Medications prohibited in the overall study are provided in the master protocol. 
6.7.3. 
Other Study Restrictions 
Other study restrictions are provided in the master protocol. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 50 of 75 
7. 
DISCONTINUATION OF STUDY TREATMENT AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of Study Treatment 
Guidance on discontinuation of study treatment is described in the master protocol. 
7.1.1. 
Liver Chemistry Stopping Criteria 
Specific guidance on liver chemistry stopping criteria is described in the master protocol in 
Section 7.1.1 and Appendix 8. Guidance on drug restart or rechallenge following liver safety 
events, if applicable, is included in Appendix 9 of the master protocol.  
7.1.2. 
QTc Stopping Criteria 
Guidance on QTc stopping criteria is described in the master protocol. 
7.2. 
Withdrawal of Consent 
Procedures to be followed in cases of consent withdrawal are presented in the master protocol. 
7.3. 
Participant Discontinuation/Withdrawal from the Study 
Examples of reasons for discontinuing study treatment or study are applicable across cohorts and 
are presented in the master protocol. 
Guidance on discontinuation of participants from the study, including required actions for 
participants lost to follow-up, is provided in the master protocol. 
7.4. 
Lost to Follow-Up 
Guidance on required actions for participants lost to follow-up is provided in the master protocol. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 51 of 75 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
8.1. 
Assessment of Efficacy 
The timing of radiologic evaluations and details regarding the evaluation of tumour response for 
both the Part 2 Safety Run-in and the Part 2 Neuroblastoma Cohort Expansion are provided in 
Table 3 and in the master protocol. Participant scan data are not routinely collected in this study; 
however, such data may be requested under special circumstances, such as during investigation 
of a significant safety event. 
8.1.1. 
Primary Efficacy Endpoint for the Neuroblastoma Cohort Expansion 
The primary efficacy endpoint for this cohort will be ORR based on Investigator assessment, 
defined as the proportion of participants who have a best overall response (BOR) of confirmed 
complete response (CR) or partial response (PR) as determined by the Investigator using INRC. 
8.1.2. 
Secondary Efficacy Endpoints for the Neuroblastoma Cohort Expansion 
The secondary endpoints for this cohort will be DOR, DCR, and PFS based on Investigator 
assessment using INRC. 
8.1.2.1. 
Duration of Response 
DOR is defined as the time from first documentation of confirmed response (CR or PR) until the 
time of first documented PD by INRC based on Investigator assessment or death (whichever 
occurs first). This will only be calculated for participants who have a BOR of confirmed CR or 
PR. Participants who do not experience PD or who die after they have had a response are 
censored at the date of their last tumour assessment. 
8.1.2.2. 
Disease Control Rate 
DCR is defined as the proportion of participants who have achieved a BOR of confirmed CR, 
confirmed PR, or stable disease by INRC based on Investigator assessment. 
8.1.2.3. 
Progression-free Survival 
PFS is defined as the time from the date of the first dose of study treatment to the first 
documented PD, as determined by INRC based on Investigator assessment, or death from any 
cause (whichever occurs first). Participants without an event will be censored at the date of the 
last tumour assessment. Participants without postbaseline assessments will be censored at the 
date of the first dose. 
8.2. 
Assessment of Safety 
Planned time points for all safety assessments are provided in Table 3. 
At some timepoints, the protocol may specify that blood samples for clinical care (i.e., clinical 
chemistry, haematology, pregnancy) and for study-related research (PK, exploratory biomarkers) 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 52 of 75 
be obtained during a single study visit. In the event of concern for excessive blood volume 
withdrawal sample collection should be prioritised as follows: 
1. clinical care 
2. niraparib PK 
3. dostarlimab PK, ADA, and NAb 
4. 
 
8.2.1. 
Safety Parameters 
Safety parameters for this study are described in the master protocol. 
8.3. 
Adverse Events and Serious Adverse Events 
Definitions and guidance on AEs and SAEs are provided in the master protocol. 
8.4. 
Pharmacokinetics, Immunogenicity, and Biomarkers  
Blood samples to assess niraparib PK, dostarlimab PK, and dostarlimab antidrug antibodies 
(ADAs) and neutralising antibodies (NAb) will be collected from all participants pre- and 
postdose at the time points specified in Table 3. 
 
 
 
 
  
Additional details concerning PK and immunogenicity sample collection are provided in the 
master protocol.  
Sample collection should be prioritised as outlined in Section 8.2. 
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 53 of 75 
8.6. 
Health Economics 
Health Economics parameters are not evaluated in this study. 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 54 of 75 
9. 
STATISTICAL CONSIDERATIONS 
An overall description of the statistics for this study is provided in the master protocol. 
Additional details are provided in the Statistical Analysis Plan. 
9.1. 
Sample Size Determination 
Part 2 Safety Run-in  
The statistical gating to initiate Part 2 Cohort Expansion will be based on minimum of 8 DLT-
evaluable participants for DLTs across osteosarcoma and neuroblastoma. When 2 or less DLTs 
and 2 or less Grade ≥3 thrombocytopenia AEs are observed, the study will continue to Part 2 
Cohort Expansion. When 3 or more DLTs are observed, the study may not continue to Part 2 
Cohort Expansion. When 2 or less DLTs and 3 out of 8 Grade ≥3 thrombocytopenia AEs are 
observed, the study may be paused for data review. If there is a differential in the DLT-evaluable 
number of participants to 8 for either endpoint, other criteria may apply and will be specified in 
the SAP. This will be the primary guideline for the dose recommendations; the totality of data 
will be taken into account. The probability of initiating Part 2 Cohort Expansion and the 
probability of pausing for data review are presented in the table below for 8 DLT-evaluable 
participants, assuming a weak correlation of 0.15 between the 2 endpoints. 
True DLT 
Rate 
True Grade ≥3 
Thrombocytopenia 
Rate 
Probability of Initiating Part 2 Cohort 
Expansion (2 or Less DLTs and 2 or 
Less Grade ≥3 Thrombocytopenia 
Events Observed Out of 8 DLT-
evaluable Participants) 
Probability of Pausing for Data 
Review (3 Grade ≥3 
Thrombocytopenia Events and 
2 or Less DLTs Observed Out 
of 8 DLT-evaluable 
Participants) 
0.25 
0.25 
49% 
13% 
0.30 
0.25 
40% 
10% 
0.30 
0.30 
32% 
13% 
0.35 
0.35 
21% 
11% 
0.45 
0.45 
6% 
6% 
Part 2 Cohort Expansion 
The sample size for this cohort is based on a Simon’s 2-stage optimal design, with a 1-sided 
alpha of 0.05 and a minimum power of 80%. The null hypothesis is ≤10% ORR, and the 
alternative hypothesis is ≥30% ORR. A futility analysis will be performed after the initial 
assessment of response for 10 evaluable participants in the cohort. If, among the 10 mITT 
participants in the cohort, at least 2 participants have objective responses (CR or PR), an 
additional 19 mITT participants will be enrolled. If 6 or more participants out of the 29 
participants enrolled have objective responses, the null hypothesis will be rejected. The required 
sample size of 29 is based on the modified Intent-to-Treat (mITT) Population. The total sample 
size to be enrolled is planned at approximately 30 in case of the potential lack of sufficient 
participants in the mITT Population. For consideration of futility, those Part 1 participants who 
satisfy the inclusion and exclusion criteria of Part 2 Cohort Expansion, satisfy the mITT 
Population definition, and are treated at the dose used in Part 2 Cohort Expansion will be 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 55 of 75 
included in the Part 2 Cohort Expansion efficacy analysis and will be counted in the required 
original Part 2 Cohort Expansion sample size. Under Protocol Amendment 05, neuroblastoma 
Safety Run-in participants who satisfy the mITT Population definition and are treated at the dose 
used in the Part 2 Cohort Expansion will also be included in the Part 2 Cohort Expansion 
efficacy analysis and will be counted in the required Part 2 Cohort Expansion sample size. The 
software for the sample size calculation is PASS 2019 (NCSS). 
9.2. 
Analysis Populations 
For the purposes of analysis, the following analysis sets are defined as follows in Table 10. 
Table 10: 
Analysis Sets 
Participant Analysis Set 
Description 
DLT-evaluable 
The DLT-evaluable Population consists of participants in 
Part 2 Safety Run-in who complete the DLT observation 
period through at least 2 cycles of study treatment 
(including ≥80% of the intended niraparib dose and ≥2 
infusions of dostarlimab) or experience a DLT for DLT 
endpoint (or Grade ≥3 thrombocytopenia AEs for the 
thrombocytopenia event endpoint). 
Safety 
The Safety Population is defined as all participants who 
receive at least 1 dose of either niraparib or dostarlimab. 
Intent-to-Treat (ITT) 
The ITT Population includes all participants who receive 
any study medication and have measurable baseline tumour 
assessment and/or metaiodobenzylguanidine-positive 
disease (MIBG) (or FDG-positive disease, for MIBG-
nonavid tumours) at baseline. 
Modified Intent-to-Treat (mITT) 
The mITT Population includes all participants who receive 
any study medication, have measurable baseline tumour 
assessment and/or MIBG-positive disease (or FDG-positive 
disease, for MIBG-nonavid tumours) at baseline, and have 
at least 1 postbaseline tumour assessment. 
Per-Protocol  
The Per-Protocol Population includes all participants in the 
mITT Population who do not have protocol violations 
during the study that may significantly impact the 
interpretation of efficacy results. 
Pharmacokinetic (PK) 
The PK Population includes all participants who receive at 
least one dose of study treatment and have at least one PK 
sample. PK Populations are defined separately for each 
agent. 
Immunogenicity (ADA) Population 
The ADA Population includes all participants who receive 
at least 1 dose of dostarlimab and who have at least 1 ADA 
sample with a result. 
 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 56 of 75 
9.3. 
Statistical Analyses 
9.3.1. 
General Considerations 
All analyses will include summary statistics, including number of participants and percentage for 
categorical variables and number of participants, mean, standard deviation, median, minimum, 
and maximum for continuous variables. Two-sided exact 95% CIs based on the Clopper-Pearson 
method will be provided where appropriate (Clopper, 1934). Time-to-event analyses will be 
performed using Kaplan-Meier methods. 
The primary analysis set for the efficacy endpoints will be the mITT Population. 
9.3.2. 
Primary Endpoints 
The primary endpoints for the Safety Run-in and Part 2 Neuroblastoma Cohort Expansion are 
defined in Section 3; the primary endpoint for the Part 2 Neuroblastoma Cohort Expansion is 
also defined in Section 8.1.1. 
For the Safety Run-in, the incidence of DLTs and incidence of Grade ≥3 thrombocytopenia AEs 
will be summarised in the DLT-evaluable Population. 
For the Part 2 Neuroblastoma Cohort Expansion, the number and proportion of participants with 
an objective response will be tabulated. ORR will be calculated, along with its estimated 2-sided 
95% CI. 
9.3.3. 
Secondary Endpoints 
The secondary efficacy endpoints for the Safety Run-in and Part 2 Neuroblastoma Cohort 
Expansion are defined in Section 3 and, for the Part 2 Neuroblastoma Cohort Expansion, also in 
Section 8.1.2. 
DCR will be calculated, along with its estimated 2-sided 95% CI. Among the participants with a 
confirmed response, a time-to-event analysis of DOR will be performed using Kaplan-Meier 
methods, including quartile estimates and 2-sided 95% CI. PFS and its 2-sided 95% CI will be 
estimated using the Kaplan-Meier method. 
9.3.3.1. 
Safety Analyses 
Safety analyses of this study are described in the master protocol. 
9.3.3.2. 
PK Analyses 
PK analyses in this study are described in the master protocol. 
9.3.3.4. 
Immunogenicity Analysis 
Immunogenicity analysis in this study is described in the master protocol. 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 57 of 75 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 58 of 75 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
The regulatory and ethical considerations of the study are outlined in Appendix 1 of the master 
protocol.  

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 59 of 75 
11. 
APPENDICES 
The following appendices in the master protocol should be referenced for the necessary guidance 
for this cohort.  
Appendix 1 
Regulatory, Ethical, and Study Considerations 
Appendix 2 
Adverse Events and Serious Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-Up, and Reporting 
Appendix 3 
Contraception Guidelines 
Appendix 4 
Not applicable to this cohort 
Appendix 5 
Guidelines for Assessment of Disease, Disease Progression, and Response Criteria in 
Participants with Neuroblastoma – Adapted from Revised International 
Neuroblastoma Response Criteria (INRC) 
Appendix 6 
List of Abbreviations and Definitions of Terms 
Appendix 8 
Liver Safety: Required Actions and Follow-up Assessments 
Appendix 9 
Liver Safety Drug Restart or Rechallenge Guidelines 
Appendix 12 
Consideration for Participants with Past HBV Infection 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 60 of 75 
APPENDIX 1. PROTOCOL AMENDMENT HISTORY 
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the Table of Contents. 
Amendment 01 (16 October 2020) 
Overall Rationale for Amendment 01 
Amendment 01 revised the protocol requirement for tumour assessments to be aligned with 
current standard of care and provides other clarifications and editorial changes catalogued since 
the issuance of the prior version of the protocol. Additionally, minor changes to the time allowed 
for safety reporting to ensure consistency with GSK standard practices.  
Summary of Changes for the Amendment 
Table 2: Summary of Changes for Amendment 01 
Section(s) Affected 
Description of Change 
Brief Rationale 
Headers, cover page, and 
Protocol Amendment Summary 
of Changes 
Headers and cover page were 
updated with new version 
number; headers were updated 
with new document number; 
Protocol Amendment Summary 
of Changes section was updated 
to include rationale for this 
version. 
Editorial changes to align with 
the Sponsor’s standard protocol 
template and ways of working 
and inclusion of specific 
language noted during Health 
Authority review 
Section 1.3 Schedule of 
Activities 
Revision to footnote for vital 
signs assessment to include 
guidance for blood pressure 
monitoring  
Deletion of minimum body 
weight criteria for PK 
parameters 
Revision of language for 
collection of information for 
SAEs and AEs 
Alignment with niraparib safety 
monitoring in accordance with 
Investigator’s Brochure, and 
Package Insert/Summary of 
Product Characteristics  
Deletion of information 
inadvertently propagated 
throughout protocol in error 
Removal of discrepant 
information and improved 
clarity 
Synopsis 
Section 1.3 Schedule of 
Activities 
Table 4 Tumour Assessment 
Flowchart 
Revision of preferred imaging 
types and schedule for scans; 
additionally, Schedule of 
Activities revised to separate 
imaging assessments according 
to different timings for standard 
of care and type of assessments 
Allowable imaging types and 
schedule revised to align with 
current standard of care 
Section 4.7.1 Procedures by 
Visit 
Revision of preferred imaging 
types and schedule for scans 
Allowable imaging types and 
schedule revised to align with 
current standard of care 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 61 of 75 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 4.7.2 General Guidance 
for Treatment Continuity when 
Participants are Unable to Come 
into the Clinic 
New section added 
Additional guidance to sites 
included in light of COVID-19  
Synopsis 
Section 5.1 Inclusion Criteria 
Minimum threshold of 
performance status reduced to 
60% in Inclusion #4 
Criteria for adequate CBC 
collection result revised to 1 
week in Inclusion #5 
Minimum threshold of absolute 
neutrophil count reduced to 
≥1,000/μL in Inclusion #5 
Revision to align with standard 
of care 
Revision to align with standard 
of care 
Revised safety monitoring 
guidance 
Section 9.2 Analysis 
Populations 
Immunogenicity populations 
included 
Provided for clarity as to 
analysis populations intended to 
be studied 
Abbreviations: AE=adverse event; CBC=complete blood count; COVID-19=Coronavirus Disease 2019; 
PK=pharmacokinetic; SAE=serious adverse event. 
Amendment 02 (23 November 2020) 
Overall Rationale for the Amendment 
Amendment 02 revises the protocol to include specific safety language noted during Health 
Authority review as detailed in Table 2. 
Summary of Changes for the Amendment 
Table 2: 
Summary of Changes for Amendment 02 
Section(s) Affected 
Description of Change 
Brief Rationale 
Headers, cover page, Protocol 
Amendment Summary of 
Changes, Appendix 1. Protocol 
Amendment History (new), and 
throughout 
Headers and cover page were 
updated with new version 
number; headers were updated 
with new document number; 
Protocol Amendment Summary 
of Changes section was updated 
to include rationale for this 
amendment and administrative 
information for prior 
amendment was moved to new 
Appendix 1. Protocol 
Amendment History. Editorial 
changes made throughout. 
Editorial changes to align with 
the Sponsor’s standard protocol 
template and ways of working, 
for conformity, clarity, flow, 
and typographical error 
correction, and for inclusion of 
specific language noted during 
Health Authority review 
Section 1.1. Synopsis (Main 
Criteria for Inclusion) 
Clarified that participants must 
not be eligible for local curative 
treatment (criterion 1) 
Participants who are eligible for 
local curative treatment are not 
permitted in the study 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 62 of 75 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 5.1. Participant 
Inclusion Criteria 
Section 1.1. Synopsis (Main 
Criteria for Exclusion)  
Section 5.2. Participant 
Exclusion Criteria 
Added language for exclusion in 
cases of pregnant or 
breastfeeding participants 
(criterion 11) 
Modified that a participant 
should not have received a live 
vaccine within 30 days of 
starting study treatment 
(criterion 20) (changed from 14 
days) 
Clarified that participants with 
QT interval prolongation >480 
ms at screening are not eligible 
and no waivers are allowed 
(criterion 22) 
Participants who are pregnant or 
breastfeeding are excluded from 
the study 
Participants must not receive 
live vaccines within 30 days of 
starting study treatment 
Participants with QT interval 
prolongation >480 ms at 
screening are not eligible for the 
study 
Section 1.3. Schedule of 
Activities/Table 3: Schedule of 
Activities (footnote c) 
Clarified that, during the 
long-term Follow-Up 
Assessment Period, follow-up 
might be conducted via a clinic 
visit or telephone contact 
To accurately reflect study 
conduct 
Section 1.3. Schedule of 
Activities/Table 3: Schedule of 
Activities, Table 4: Tumour 
Assessment Flow Chart 
Updated Table 3 and Table 4 to 
reflect editorial updates made in 
the master protocol 
To align with the master 
protocol 
Section 5.3. Lifestyle 
Considerations 
Added that participants should 
avoid exposure to ultraviolet 
light and take precautions when 
exposed to direct sunlight 
Added due to the fact that 
photosensitivity has been 
reported for patients receiving 
niraparib 
 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 63 of 75 
Amendment 03 (20 Jul 2022) 
Overall Rationale for Amendment 03: 
• To update secondary objective and/or endpoint for PK and immunogenicity. 
• To update inclusion and exclusion criteria. 
• To increase clarity and/or remove discrepancies. 
All changes are listed in table below. 
Table 2: 
Summary of Changes for Amendment 03 
Section(s) Affected 
Description of Change 
Brief Rationale 
Headers, title page, Protocol 
Amendment Summary of 
Changes, Appendix 1. Protocol 
Amendment History, and 
throughout 
Headers and cover page were 
updated with new version 
number; headers were updated 
with new document number; 
Protocol Amendment Summary 
of Changes section was updated 
to include rationale for this 
amendment and administrative 
information for prior 
amendment was moved to 
Appendix 1. Protocol 
Amendment History. Editorial 
changes made throughout. 
Editorial changes to align with 
the Sponsor’s standard protocol 
template and ways of working 
Title page 
Updated compound number 
“GSK4057190 to 
GSK4057190A” 
To present current correct 
compound number 
Section 1.1 Synopsis (Secondary 
objectives) 
Section 3 Study Objectives and 
Endpoints 
Added new secondary objective; 
to assess the immunogenicity of 
dostarlimab in paediatric 
participants 
To correct lack of secondary 
objective given immunogenicity 
analyses are described in the 
protocol and an immunogenicity 
population is defined in Section 
9 Statistical Considerations 
Section 1.1 Synopsis: 
(Methodology) Data Review 
Committee  
Updated information for 
establishment and composition 
of an independent data oversight 
committee 
To clarify that a committee that 
is independent of all aspects of 
the study and that is dedicated to 
oversight of safety and efficacy 
data from participants in Part 2 
will be established. To clarify 
that details of committee 
composition and function will 
be described in a formal charter. 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 64 of 75 
Section(s) Affected 
Description of Change 
Brief Rationale 
To indicate that the RP2D 
 
 as 
determined in Part 1A of the 
study is the dose that is to be 
advanced and evaluated in Part 
2 of the study. 
Section 1.1. Synopsis 
(Diagnosis and Main Criteria for 
Inclusion: criterion 2) 
Section 5.1. Participant 
Inclusion Criterion (criterion 2) 
Deleted: Measurable disease in 
participants with central nervous 
system (CNS) involvement is 
defined as a tumour that is 
measurable in 2 perpendicular 
diameters on MRI and visible on 
more than 1 slice. 
Added text for 
measurable/evaluable disease 
and for bone only 
neuroblastoma. 
To remove text that was not 
directly applicable to 
measurement of disease in 
neuroblastoma 
To further clarify exactly what 
type of disease would be 
considered 
measurable/evaluable. 
Section 1.1. Synopsis 
(Diagnosis and Main Criteria for 
Inclusion: criterion 6) 
Section 5.1. Participant 
Inclusion Criterion (criterion 6) 
Updated note describing timing 
for collection of blood sample 
for complete blood count 
To better describe a correct and 
more reasonable washout period 
for support agents (transfusion, 
colony-stimulating factors, 
erythropoietin) received prior to 
collection of blood for complete 
blood count during screening.  
Section 1.1. Synopsis 
(Diagnosis and Main Criteria for 
Exclusion: criterion 10) 
Section 5.2. Participant 
Exclusion Criteria (criterion 10) 
Removed bullets on blood 
transfusion and growth factors 
in exclusion criterion 10 
Permitted window prior to first 
dose of study treatment has been 
updated in inclusion criterion 5. 
The permitted windows in 
exclusion criterion 10 no longer 
are applicable and, therefore, 
were removed. 
Section 1.1. Synopsis 
(Diagnosis and Main Criteria for 
Exclusion: criterion 15) 
Deleted original exclusion 
criterion 15 (this text was 
combined with text for 
exclusion criterion 19 as 
To update exclusion criteria to 
include additional criterion to 
support participant safety. 
CCI
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 65 of 75 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 5.2. Participant 
Exclusion Criteria (criterion 15) 
described below) and replaced 
with “Participant must not have 
a gastrointestinal condition, such 
as bowel obstruction, that can 
impact absorption of oral 
medications and is identified by 
clinical symptoms or CT scan, 
etc” 
Section 1.1. Synopsis 
(Diagnosis and Main Criteria for 
Exclusion: criterion 16) 
Section 5.2. Participant 
Exclusion Criteria (criterion 16) 
Updated exclusion criteria 16 to 
clarify guidance on hematologic 
side effects from prior 
anticancer therapy. 
To clarify information on 
excluded cytopenia occurrence 
and duration 
Section 1.1. Synopsis (Main 
Criteria for Exclusion: criterion 
18)  
Section 5.2: Participant 
Exclusion Criteria (criterion 18) 
Added new exclusion criteria 
“Toxicity related to prior 
immunotherapy that led to study 
treatment discontinuation.” 
To include guidance for 
enrolment of patients who had 
previously experienced toxicity 
in response to immunotherapy 
and to align eligibility 
requirements with those of 
dostarlimab protocols in general. 
Section 1.1. Synopsis 
(Diagnosis and Main Criteria for 
Exclusion: criterion 19) 
Section 5.2. Participant 
Exclusion Criteria (criterion 15) 
Section 5.2. Participant 
Exclusion Criteria (criterion 19) 
Deleted original exclusion 
criterion 15. 
Updated exclusion criterion 19 
to clarify permitted window 
relative to first dose of study 
treatment for prior systemic 
anticancer therapy. Combined 
text from exclusion criterion 15 
with text in exclusion 
criterion 19. 
To update permitted window for 
receipt of prior anticancer 
therapy from “within 3 weeks” 
prior to first dose of study 
treatment to “within 3 weeks or 
5 half-lives, whichever is 
shorter” - a change which was 
made in response to an 
investigator suggestion and 
which reflects half-life data for 
most common standard of care 
therapies enrolled patients with 
the specified tumour types.  
In addition, to make the 
excluded window consistent for 
investigational agents or devices 
and for approved systemic 
therapies of all types. 
Section 1.1. Synopsis 
(Diagnosis and Main Criteria for 
Exclusion: criterion 23) 
Section 5.2. Participant 
Exclusion Criteria (criterion 23) 
Updated exclusion criterion 23 
with corrected QTc values  
To align excluded QTc values 
with values appropriate for 
participants to be treated with 
dostarlimab. 
Section 1.1. Synopsis 
(Diagnosis and Main Criteria for 
Exclusion: criterion 24) 
Added exclusion criteria 24 to 
clarify that solid organ 
transplant is not permitted. 
To prohibit enrolment of 
participants who are receiving 
immunosuppressive therapy that 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 66 of 75 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 5.2. Participant 
Exclusion Criteria (criterion 24) 
might impact effectiveness of 
dostarlimab as a PD-1 inhibitor. 
Section 1.1. Synopsis (Analysis 
Population) 
Section 9.2 Analysis Population 
Table 7 
Revised definition of PK 
population and immunogenicity 
populations 
Updated the description of the 
intent-to-treat population and 
modified intent-to-treat 
population 
To more accurately describe 
which participants qualified for 
inclusion in each population 
To more completely describe the 
relevant population for 
participants with neuroblastoma 
Section 1.3. Schedule of 
Activities (Table 3) 
Added “Post-Treatment” to 
column header for FUP 
assessment Period 
To align column header content 
with text clarifying that Follow-
up visits were to occur every 
90 days following end of study 
treatment.  
Section 1.3 Schedule of 
Activities (Table 3) 
Removed -10-day window from 
Screening period 
To correct outside limit of 
Screening activities window to -
28 days rather than -28 days +10 
additional days. 
Section 1.3. Schedule of 
Activities (Table 3 and Footnote 
j) 
Addition of pregnancy testing 
for WOCBP at End of 
Treatment and 30-day Safety 
Follow-up Visits 
To ensure pregnancy did not 
occur during the excluded 
period.  
Section 1.3. Schedule of 
Activities (Table 3 and Footnote 
l) 
Addition of 12-lead ECG testing 
added in Cycle 3 
In line with study level 
requirements 
Section 1.3 Schedule of 
Activities (Table 3 and Footnote 
q, r) 
Added text indicating that 
tumour assessments should be 
conducted every 9 weeks (every 
63 [±7] days) from the start of 
study treatment for the first 12 
months and then every 12 weeks 
(every 84 [±7] days) thereafter, 
To reduce total number of scans 
conducted throughout duration 
of participant enrolment and 
thereby reduce radiation 
exposure overall. 
Section 1.3 Table 3 Schedule of 
Activities 
Merged cells for EOT Visit, 
Safety FUP Visit, and FUP 
Assessment Period for the rows 
for several disease assessment 
activities  
To clarify that measures of 
disease assessment are to 
continue throughout the EOT 
and follow-up periods. 
Section 1.3. Schedule of 
Activities (Table 3 Footnote b) 
Added additional details on 
safety FUP visit 
To clarify the Safety FUP visit 
window 
Section 1.3. Schedule of 
Activities (Table 3 Footnote c) 
Clarified long-term follow-up 
assessment period 90 (±14) days 
“after the last dose of study 
treatment” 
To clearly define specific 
starting point from which to 
initiate long-term follow-up 
safety assessments 
Section 1.3. Schedule of 
Activities (Table 3 Footnote i) 
Updated to replace baseline with 
“Cycle 1 Day 1” and to clarify 
To clarify that if the screening 
laboratory samples were 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 67 of 75 
Section(s) Affected 
Description of Change 
Brief Rationale 
guidance for Cycle 1 Day 1 
sample collection. 
collected within 7 days prior to 
Cycle 1 Day 1, then collection 
of these samples did not need to 
be repeated for Cycle 1 Day 1. 
Section 1.3 Schedule of 
Activities (Table 3 Footnote m) 
Removed the language that 
“MRI should only be used if 
clinically appropriate, when CT 
is contraindicated, and 
preferably for imaging of the 
brain” 
To remove restrictions to use of 
MRI in medically appropriate 
scanning situations  
Section 1.3 Schedule of 
Activities (Table 3 Footnote v) 
Added text clarifying required 
duration of AE collection 
To clarify that collection of AEs 
is to continue throughout the 
required 30-day interval even in 
the event of initiation of 
additional anticancer treatment. 
Section 1.3 Schedule of 
Activities (Table 3 Footnote y) 
Added text clarifying collection 
interval for PK sample 
collection 
To clarify that timing of PK 
sample collection is relative to 
time of participant’s very first 
dose of niraparib. 
Section 1.3. Schedule of 
Activities (Table 3 Footnote w, 
x and z) 
Updated information for 
dostarlimab PK, ADA, 
neutralising antibodies, and 
biomarker sample collection 
To provide additional guidance 
for procedures and timing of 
dostarlimab PK, ADA, and 
biomarker sampling. 
Section 2.4 Benefits and Risks 
Assessment 
Added new section and referred 
to master protocol  
To align content of protocol 
with that of GSK standard 
template 
Section 3 Study Objectives and 
Endpoints 
Revised PK endpoint 
To describe the parameters 
constituting the endpoint 
measures. 
Section 6.3. Measures to 
Minimize Bias: Randomization 
and Blinding 
Added “non-randomized” 
To clarify study design. 
Section 6.4. Study Treatment 
Compliance 
Added “dostarlimab and 
niraparib during dostarlimab 
infusion visits”. 
To clarify exactly what study 
treatment would be administered 
to the participant at the research 
site and when this treatment 
would be administered.  
Section 6.5 Dose Modification 
Added clarifying text 
To clarify that guidance in first 
paragraph of Section 6.5 is 
applicable to dostarlimab. To 
include reference to Section 4.7 
in the master protocol for full 
dose modification guidance.  
Section 6.8 Treatment 
Compliance 
Deleted this Section 
To remove text that had already 
been presented in the protocol in 
Section 6.4. 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 68 of 75 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 7.1.2 QTc Stopping 
Criteria 
Added new section on QTc 
stopping criteria referring to 
master protocol 
To align with safety monitoring 
requirements for dostarlimab 
Section 8.1.2 Secondary 
Efficacy Endpoint 
Added text for scan data 
collection 
To establish that while scan data 
are not routinely collected in the 
study, these data may be 
collected under special 
circumstances. 
Section 8.4 Pharmacokinetics, 
Immunogenicity and 
Biomarkers 
• 
Added text from Master 
protocol Section 8.4 on PK 
sampling. 
To provide additional detail in 
this supplement protocol on PK 
sampling requirements.  
Section 9.3.3 Secondary 
Endpoints, Section 9.3.4 Interim 
Analysis, and Section 9.3.5 
Exploratory Analysis 
Reordered sections / subsections 
Reordered sections/ subsections 
to more clearly present planned 
analyses. 
Section 11 Appendices 
Updated Appendix numbers and 
added new Appendix 5 
Guidelines for Assessment of 
Disease, Disease Progression, 
and Response Criteria in 
Participants with Neuroblastoma 
– Adapted from Revised 
International Neuroblastoma 
Response Criteria (INRC) and 
cross refereed to master protocol 
To direct the reader to the 
appropriate guidance in the 
master protocol for assessing 
response in participants with 
neuroblastoma.  
 
Amendment 04 (23 May 2024) 
Overall Rationale for Amendment 04: 
Amendment 04 is a global amendment resulting in changes in participant dosing based on the 
participant’s age. Administrative, editorial, and clarifications for study conduct are also included. 
A general description and brief rationale(s) for the key changes are provided in Table 2 below. 
The synopsis was also updated to align with the changes in the protocol body. 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 69 of 75 
Table 2: Summary of Changes for Amendment 04 
Section(s) Affected 
Description of Change 
Brief Rationale 
Headers, Title Page, abbreviations, 
Protocol Amendment Summary of 
Changes, List of Abbreviations, 
Appendices, References, and 
throughout 
Section 6 Study Treatment(s) and 
Concomitant Therapy 
Headers and title page updated with 
new document numbers, dates, and 
amendment information; Protocol 
Amendment Summary of Changes 
section was updated to include details 
and rationales for this amendment; 
administrative changes, editorial 
revisions for consistency with Sponsor’s 
ways of working, minor corrections and 
formatting adjustments, and to add 
clarification and/or remove 
discrepancies 
Editorial changes to align with the 
Sponsor’s standard protocol template, 
style guide, and ways of working and 
regulatory changes, and for accuracy, 
clarity, conformity, flow, and 
typographical error correction. 
Throughout 
• Use of 
 changed to 
 
throughout the document, including 
 details and use of 
 going 
forward, as applicable 
 is the selected 
 
 developed by 
the applicant for use in participants and 
is a term commonly used by the 
Sponsor’s formulation development and 
manufacturing groups 
Section 1.3 Schedule of Assessments 
(Table 3, footnotes) 
Section 1.2 Schemas, Figure 1 (new) 
Section 2 Introduction 
Section 3, Table 5 Objectives and 
Endpoints for Study 213406 
Section 4.1 Overall Design 
Section 4.1.1 Dose Limiting Toxicity 
Section 4.2 Number of Participants 
Section 4.4 Dose Adjustment Criteria 
Section 4.4.1 Dose Adjustment Criteria 
for Age and Weight 
Section 4.4.2 Dose Adjustment for AEs 
Section 4.4.3 Niraparib 
Section 4.4.4 dostarlimab 
Section 5.1 Participant Inclusion 
Criterion 
Section 6.1 Study Treatments 
Administered; Table 9: Investigational 
Products 
Section 8.1 Assessment of Efficacy 
Section 9.1 Sample Size Determination 
Section 9.2 Analysis Populations 
Section 9.3.2 Primary Endpoints 
Section 9.3.3 Secondary Endpoints 
• New figure outlining Part 2 study 
design 
• Footnotes updated in SoA regarding 
monitoring/PK sample collection with 
changes in niraparib dose during the 
study per the updated dosing 
regimens based on weight and age 
• Introduction and study objectives 
and endpoints updated to include 
the Safety Run-in Cohort 
participants 
• Update overall design to reflect 
updated dosing and details of Safety 
Run-in 
• Section 4.4.1 and Section 4.4.2 
added outlining dose adjustments for 
age and weight and AEs in Part 2 
• Section 4.4.3 included for guidance 
on niraparib dose reductions and 
Table 6, Table 7, and Table 8 added 
outlining modifications for AEs, 
nonhematologic adverse reactions, 
and haematologic adverse reactions, 
respectively 
• Subsection included referring to 
dostarlimab dose modification 
• Inclusion criterion #3 – updated to 
outline age enrolment requirements 
under Amendment 04 
• Inclusion criterion #4 – updated to 
reflect no requirement for ability to 
swallow as a result of 
 
formulation being used going 
forward 
Changes to proposed dosing regimens 
for niraparib and study design, following 
study enrolment pause and data 
evaluation to ensure appropriate dosing 
of participants with the combination, 
including additional cohorts to evaluate 
additional dose levels 
Minor editorial changes to endpoints 
and objectives for clarification. 
CCI
CCI
CCI
CCI
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 70 of 75 
Section(s) Affected 
Description of Change 
Brief Rationale 
• Number of participants updated to 
include Safety Run-in Cohort 
patients 
• Study treatment information sections 
update to include 
 details  
• Including update to Investigation 
products table to align with 
regulatory requirements 
• Sample size text updated to reflect 
addition of Safety Run-in 
• Updated assessment of efficacy 
section and statistical analyses 
sections to include Safety Run-in 
information, definition for DTL-
evaluable Population 
Section 3, Table 5 Objectives and 
Endpoints for Study 213406 
9.3.5 Exploratory Analysis 
• Exploratory endpoints updated to 
adjust wording for exploratory 
biomarker objective and endpoint 
language as well as exploratory 
analysis 
To provide further details and more 
clarity about the planned exploratory 
analysis.  
Section 5.1 Participant Inclusion 
Criteria 
• Inclusion criterion #6: organ function 
parameters updated for haemoglobin 
To align with the patient population 
Section 1.3 Schedule of Assessments 
(Table 3, footnote) 
Section 5.1 Participant Inclusion 
Criteria (criterion #7c) 
• Clarification included that WOCBP 
must have a pregnancy test even if 
they had received treatment that 
potentially but not definitely would 
prohibit becoming pregnant 
• Timeline for providing negative 
pregnancy test result updated to 
24 hours 
Updated to increase assurance that 
female participant of childbearing 
potential is not pregnant as close as 
possible to time of study drug dosing 
Section 5.2 Participant Exclusion 
Criteria 
• Exclusion criterion #7 – clarification 
participants with previously treated 
CNS metastases for evidence of 
disease progression 
Updated text to provide more accurate 
description of changes indicative of 
progression of disease in brain. 
Section 5.2 Participant Exclusion 
Criteria 
• Exclusion criterion #11 – updated 
language regarding when 
breastfeeding can resume 
To align with guidance in current US 
prescribing information for niraparib 
and dostarlimab 
Section 5.2. Participant Exclusion 
Criteria 
• Exclusion criterion 14 – updated 
wording regarding HbsAg/HbcAb for 
HBV screening 
To permit the inclusion of patients with 
past HBV infection 
Section 5.2. Participant Exclusion 
Criteria 
• New exclusion criteria #25 and #26 
added regarding HCV testing  
To align with current protocol template 
language 
Section 5.2. Participant Exclusion 
Criteria 
• Exclusion criterion #17 – updated 
language regarding AEs in 
participants undergoing systemic 
anticancer therapy with exceptions 
as agreed with Sponsor. 
Expansion of text to more clearly define 
conditions for participant eligibility. 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 71 of 75 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 1.3 Schedule of Assessments 
(Table 3)  
Section 2.2 Rationale for Tumour Type 
• 
 
Editorial change for clarification 
Section 5.1. Participant Inclusion 
Criteria 
• Inclusion criterion #1 – replaced 
statement ‘local curative 
treatment.' with ‘alternative 
curative treatment.' 
Clarification 
Section 5.1 Participant Inclusion criteria 
• Inclusion criterion #10 – updated 
clarifying tumour tissue sample 
requirements 
Clarification 
Section 1.3. Schedule of Activities 
(Table 3, including footnotes) 
Section 4.4 General Study Conduct 
Section 8.4 Pharmacokinetics, 
Immunogenicity, and Biomarkers 
• Update to blood sample collection for 
niraparib PK  
• Adjusted table and added clarifying 
footnote for blood sampling for 
dostarlimab PK and/or ADAs and 
neutralising antibodies (NAb) at 
Safety FUP Visit and FUP 
Assessment Period 
• Updated language regarding 
collection of blood samples and 
storage 
Clarification for study conduct and 
alignment with Sponsor requirements 
for sample storage 
Section 1.3 Schedule of Assessments 
(Table 3 and Table 4; including 
footnotes) 
Table 4 Tumour Assessment Flowchart 
• Clarification that brain scans must 
include IV contrast and brain scan by 
MRI preferred to that by CT including 
in table footnote and Table 4 
outlining tumour assessments 
• Wording and footnote updates in 
SoA for clarifications including 
aligning discontinuation wording 
throughout. 
Clarification for study conduct 
Section 1.3 Schedule of Assessments 
(Table 3; footnote) 
Section 8.2 Assessment of Safety 
Section 8.4 Pharmacokinetics, 
Immunogenicity, and Biomarkers 
• Detail included regarding 
prioritisation of blood sample 
collection in the event of concerns for 
excessive blood volume withdrawal 
Clarification for study conduct to 
provide guidance to sites on relative 
importance of collection of specific 
blood samples  
Section 1.3 Schedule of Assessments 
(Table 3; including footnote) 
8.4.1 exploratory biomarkers 
• Updated language regarding 
collection and analysis of biomarker 
samples and processing  
Clarification 
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 72 of 75 
Section(s) Affected 
Description of Change 
Brief Rationale 
Section 1.3. Schedule of Activities 
(Table 3; including footnote) 
• Updated timing for collection of vital 
signs, height, and weight 
measurements including during 
follow-up period and clarifications for 
measuring height and weight 
• 
 
 
 
  
• Adjusted wording surrounding 
collection and follow-up of 
nonserious AEs, and expectations 
for follow-up of SAEs during long-
term follow-up period and when 
starting alternative anticancer 
therapy 
Clarification for study conduct, including 
adjusted language to permit consistent 
monitoring of vital signs throughout the 
Treatment Period. 
Section 8.5 Genetics 
• Updated language outlining DNA 
analysis 
Clarification 
Abbreviations: 
; ADA(s)=antidrug antibody(ies); AE(s)=adverse event(s); 
; CBC=complete blood count; CNS=central nervous system; CT=computed tomography; 
DLT=dose limiting toxicity(ies); FUP=follow-up; GFR=glomerular filtration rate; HbcAb=hepatitis B core antibody, HBsAg = 
hepatitis B surface antigen; HBV = hepatitis B virus; HCV=hepatitis C virus; INRC=International Neuroblastoma Response 
Criteria; MRI=magnetic resonance imaging; MIBG-SPECT=metaiodobenzylguanidine-single photon emission computed 
tomography/computed tomography; PK=pharmacokinetics; RECIST=Response Evaluation Criteria in Solid Tumours; 
SAE(s)=serious AE(s); SoA=schedule of assessments; 
; WOCBP=woman of childbearing 
potential; US=United States.  
 
Amendment 04 GBR-1(08 Aug 2024)  
Overall Rationale for Amendment 04 GBR-1: 
Amendment 04 GBR-1 is a UK-specific amendment addressing agency feedback regarding 
exclusion criterion 17. A description and rationale for the changes is provided in Table 2 below.  
 
Table 2: Summary of Changes for Amendment 04 GBR-1 
Section(s) Affected 
Description of Change (deleted text; added text) 
Brief Rationale 
Headers, Title Page, Protocol 
Amendment Summary of Changes, 
Appendix 2 Country-specific 
Requirements 
Headers and title page updated with new 
amendment number/approval date, and amendment 
information; Protocol Amendment Summary of 
Changes section was updated to include details and 
rationale for this amendment; country-specific 
appendix for global amendments removed and 
associated text in protocol sections/tables adjusted. 
Editorial changes to align with 
the Sponsor’s standard 
protocol template, style guide, 
and ways of working. 
CCI
CCI
CCI
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 73 of 75 
Section(s) Affected 
Description of Change (deleted text; added text) 
Brief Rationale 
Synopsis 
Section 5.2 Participant Exclusion 
Criteria 
Exclusion criterion #17 updated as follows: 
Participant has not recovered (i.e., to Grade ≤1 or to 
baseline) from systemic anticancer therapy-induced 
AEs. Note: Participants with certain AEs that are 
considered either nonclinically significant or are 
deemed stable or irreversible are exceptions to this 
criterion and may qualify for the study after 
discussion with the GSK Medical Monitor. Examples 
of AEs include, but are not limited to, alopecia, 
hearing impairment, alopecia, Grade ≤2 
neuropathy, Grade ≤2 fatigue, Grade ≤2 anaemia, 
and/or Grade ≤2 neutropenia are an exception to 
this criterion and may qualify for the study. 
Regulatory agency feedback. 
 

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 74 of 75 
CCI

CONFIDENTIAL 
GSK group of companies 
Protocol 213406 Supplement B 
Protocol Amendment 05 
Page 75 of 75 
12. 
LIST OF REFERENCES  
Clopper C and Pearson ES. The use of confidence or fiducial limits illustrated in the case of the 
binomial. Biometrika. 1934;26:404-413. 
Steliarova-Foucher E, Colombet M, Ries LAG, Moreno F, Dolya A, Bray F, et al. International 
incidence of childhood cancer, 2001-10: a population-based registry study. Lancet Oncol. 
2017;18(6):719-731. 

Signature Page for  213406 TMF-20143934 v1.0
Signature Page for TMF-20143934 v1.0
Reason for signing: Approved
Name:
Role: Approver
Date of signature: 17-Dec-2024 15:55:25 GMT+0000
PPD