A Phase II Multicenter, Open-Label, Single Arm Study to Determine the Efficacy, Safety and Tolerability of AZD2811 and Durvalumab Combination as Maintenance Therapy After Induction With Platinum-Based Chemotherapy Combined With Durvalumab, for the First-Line Treatment of Patients With Extensive Stage Small-Cell Lung Cancer
Phase: PHASE2
Conditions: Small-Cell Lung Cancer
Sponsor: AstraZeneca

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Clinical Study Protocol 
Study Intervention
AZD2811 + durvalumab
Study Code
D6132C00001
Version
9.0
Date
21 April 2022
A Phase II Multicenter, Open-Label, Single Arm Study to 
Determine the Efficacy, Safety and Tolerability of AZD2811 and 
Durvalumab Combination as Maintenance Therapy After 
Induction with Platinum-Based Chemotherapy Combined with 
Durvalumab, for the First-Line Treatment of Patients with 
Extensive Stage Small-Cell Lung Cancer 
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Sponsor Name: 
Legal Registered Address: AstraZeneca AB, 151 85 Södertälje, Sweden.
Regulatory Agency Identifier Number: EudraCT Number 2020-004091-18, IND Number 
152711
This Clinical Study Protocol has been subject to a peer review according to AstraZeneca 
Standard procedures. The Clinical Study Protocol is publicly registered and the results are 
disclosed and/or published according to the AstraZeneca Global Policy on Bioethics and in 
compliance with prevailing laws and regulations.
Protocol Number: D6132C00001
Amendment Number: 8
Study Intervention: AZD2811 + durvalumab
Study Phase: 2
Short Title: Phase II maintenance study of AZD2811 + durvalumab in ES-SCLC.
Study Physician Name and Contact Information will be provided separately
International co-ordinating investigator
 
 
Houston, 
Texas, USA.
PPD

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VERSION HISTORY
Version 9, 30 March 2022 (Amendment 8) 
!
Introduced global changes to align with the the decision to terminate enrolment for this
study prior to completion due to the evolving benefit risk profile of AZD2811 that does
not support further development for the first-line treatment of patients with extensive
stage small-cell lung cancer. Patients already enrolled in the study were able to
continue. However, no further patients were permitted to start AZD2811 treatment and
ongoing patients transitioning into the maintenance phase in the future were offered
durvalumab monotherapy. As a result of the early termination, the data cut-off for the
final analysis in this study is planned for 18 June 2022.
!
Sections from CSP v8.0 are retained throughout this protocol for reference. Clinical
Study Protocol v8.0 was prepared to include urgent safety measures via a Dear
Investigator Letter; however, CSP V 8.0 was not implemented due to early termination.
Clinical Study Protocol v8.0 is superseded by CSP v9.0.
!
Global change – blood samples for
were reverted 
back to timepoints indicated in the previously approved CSP. 
!
Global change – The abbreviated CSR will focus on reporting safety endpoints as there
were too few patients who received AZD2811 in combination with durvalumab
(9 patients) to give meaningful analyses. The efficacy analyses will be streamlined and
this will be fully documented in the SAP.
!
Table 2 and Table 4 – Addition of +/- 1 week to the Follow-up visit.
!
Section 9.4.6 –
!
Administrative changes for clarity and consistency throughout.
Version 8, 10 December 2021 (Amendment 7) 
!
Introduced global changes to align with the Dear Investigator Letter, dated
11 October 2021.
!
Administrative changes for clarity and consistency throughout.
!
Global change- Changed maximum starting dose of AZD2811 in the Maintenance
Phase to 
 (previously 
) and added that the study aims to achieve 
80 evaluable participants on the starting dose of 
.
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Global change- Added that if short-acting G-CSF is used, it should be administered 
daily until at least 
 of each cycle and until the ANC has recovered to
≥1.5 × 109/L.
!
Global change- Clarified that where possible, every effort should be made to schedule 
the scan within 1 week prior to dosing with AZD2811; scan results must be reviewed 
prior to dosing to confirm the absence of disease progression
!
Synopsis- Updated to align with changes in main body of CSP.
!
Table 1- Clarified CT scan to be performed during 
 
 scan, to confirm eligibility for maintenance phase.
!
Table 1 and Table 3-
 
.
!
Table 2- Added that an AE/SAE assessment is required every 2 months +/-1 week after 
the 90 day follow-up for participants not entering the maintenance phase.
!
Table 3, Section 4.1.2.1, and Section 5.3- Added that eligibility criteria for the
maintenance phase must be confirmed prior to dosing with AZD2811.
!
Table 3 – Added mandatory assessments on Day 12 of Cycle 5 and Cycle 6: vital signs; 
concomitant medications; AE/SAE assessment; hematology; and blood sample for 
AZD2811 PK (postdose).
!
Table 3- Clarified that a blood sample for durvalumab PK (predose) is not required 
beyond Day 1 of Cycle 7.
!
Table 3-
 
!
Table 3-
 
!
Table 3-
 
 
!
Table 3-
 
 
!
Table 3, Section 4.1, and Section 8.1- Clarified when RECIST v1.1 tumor assessments 
should be performed and that these scans must be reviewed prior to dosing of 
AZD2811.
!
Table 3 and Section 7.1- Clarified that for participants receiving durvalumab 
monotherapy, only Day 1 visits and assessments must be completed.
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Table 3 and Table 5- Removed text stating ‘G-CSF must be discontinued 48 hours
prior to the next dose of AZD2811. Complete blood counts should be collected and
reviewed on Day 8 and/or Day 15.’These details can be found in Section 6.2.4.
!
Table 4- Specified that, for several samples, blood does not need to be drawn for
participants who received re-treatment after relapse.
!
Table 6- Updated sepsis to be an identified risk, rather than a potential risk, associated
with AZD2811.
!
Table 6- Updated pancreatitis and encephalitis to be identified risks, rather than
potential risks, associated with durvalumab.
!
Table 6- Removed non-infectious encephalitis as a potential risk for durvalumab.
!
Section 4.1- Clairified that global recruitment will be complete when a minimum of
80 evaluable participants have entered the maintenance phase.
!
Section 4.1.2.2- Clarified that if a DLT event is observed in the safety run-in study
treatment will be paused for new participants entering the maintenance phase, while
the SRC convenes.
!
Section 4.1.2- Divided section into 3 subheadings: Section 4.1.2.1 Maintenance Phase
Overview; Section 4.1.2.2 Safety Run-In; and Section 4.1.2.2.1 Results of the Safety
Run-In
!
Section 4.1.2.1- Clarified that participants with disease progression should not continue
treatment with durvalumab monotherapy if there are any significant, unacceptable or
irreversible toxicities.
!
Section 4.1.2.2- Clarified that if transition of participants to maintenance therapy is
paused, patients may receive durvalumab monotherapy during the pause and will be
allowed to start AZD2811 therapy after the pause if eligibility criteria are met.
!
Section 4.1.2.2.1- Added summary of the results of the safety run-in cohort and
associated list of proposed protocol amendments.
!
Section 4.1.2.2.1- Added list of proposed protocol amendments following the results of
the Safety Run-In.
!
Section 4.1.2.2.1- Added that after implementation of the proposed protocol
amendments in CSP v8.0, an additional safety run-in cohort will be assessed by the
SRC.
!
Table 9 and Table 13- Updated SC dose of filgrastim to 0.5 MU (5 μg)/kg/day and
removed IV dose.
!
Section 4.1.4- Changed heading to “Definition of DLT-Evaluable Participants” from
previous heading of “Definition of Evaluable Patients”.
!
Section 4.1.4- Corrected table number from Table 1 to Table 3.

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Section 4.3.2- Added that subsequent to the review of the safety run-in, the starting
dose of AZD2811, in combination with durvalumab in the maintenance phase, has
been reduced to a maximum of 
!
Section 5.1 and Section 5.2- Changed headings to “Induction Phase
Inclusion/Exclusion Criteria” from previous headings of “Inclusion/Exclusion
Criteria”.
!
Section 5.3.1 and Section 5.3.2- Added inclusion and exclusion criteria for
maintenance phase.
!
Section 6.1.2- Clarified that following permanent discontinuation of any chemotherapy
agent as a result of toxicity, participants may enter the maintenance phase after
consultation with the Study Physician and if they meet the maintenance phase
eligibility criteria.
!
Section 6.1.3- Clarified that upon initial assessment of PD, treatment with AZD2811
must be discontinued but that treatment with durvalumab may be continued until
radiological PD is confirmed.
!
Section 6.2.4- Clarified when CBCs should be collected and reviewed.
!
Section 6.5.1.1 and Section 8.5.1- Added that AZD2811 dosing should be delayed if
there is any suspicion that a patient is suffering from an infection.
!
Section 6.5.1.1- Added (prophylactic) antibiotics to list of permitted concomitant
medications in patients who: are experiencing Grade 4 neutropenia; are at high risk of
infection; or have a suspected infection.
!
Section 6.5.2.1 and Table 15- Added that herbal supplements that strongly modulate
CYP3A4 must not be used during the maintenance phase.
!
Section 6.6.2- Clarified that dosing may be delayed due to an immune or a
non-immune-related AE and, if delayed for reasons other than treatment-related
toxicity, will resume as soon as feasible.
!
Section 6.6.2- Updated the period of time the durvalumab dose may be delayed for,
from 6 weeks, up to a maximum of 12 weeks from initiation of corticosteroids.
!
Section 8.1- Added that an unscheduled imaging assessment should be performed if
disease progression is suspected.
!
Section 8.2- Added that participants who enter the Maintenance Phase on durvalumab
monotherapy and subsequently receive AZD2811 in a later cycle require additional
safety assessments and PK sampling.
!
Section 8.2.3- Corrected sentence to ‘triplicate 12-lead ECGs (about 5 minutes apart)
pre- and post-AZD2811 and pre- and post-durvalumab infusion should be performed.’
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Table 17- Added footnote for CRP.
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Section 8.2.5- Added that participants will also be evaluated on
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Table 21- Clarified that if any toxicity does not resolve to Grade 1 or revert to baseline
within 14 days, AZD2811 treatment must be discontinued.
!
Table 21- Clarified that participants can only be dosed with AZD2811 on Day 1 of any
Cycle if ANC is ≥ 1.5 × 109/L and platelet count is ≥ 75 × 109/L.
!
Table 21- Clarified that AZD2811 should be held until Grade 2-3 ANC or Grade 2-3
thrombocytopenia (without bleeding or requirement for platelet transfusion) has
resolved and then restarted at the same dose prior to the event.
!
Section 8.6.2.2- Added wording ‘will be collected’ to clarify that mandatory fresh
on-treatment tumor biopsies will be collected until core biopsy samples meeting the
specified criteria are received.
!
Section 8.6.2.6 and Section 8.6.2.10- Added additional timepoints for collection of
blood samples in line with Table 3.
!
Section 9.2- Changed sample sizes.
!
Table 23, Section 9.4.2.1, and Section 9.4.2.2- Clarified that only patients who
received 
AZD2811 + durvalumab on 
 will be included in 
evaluation of primary and secondary endpoints.
!
Appendix F4- Updated to reflect clarifications to tumor response evaluation timepoints
throughout CSP.
!
Appendix H2 and Section 11- Removed reference for Silva et al, 2011.
Version 7, 29 June 2021 (Amendment 6)
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Table 21-Hematologic Toxicity criteria for neutropenic dose reductions updated to
align with the Phase 1 (D6130C00001) study and associated data
Version 6, 17 May 2021 (Amendment 5)
!
Tables 1-5 Schedule of Activities: Updated Notes column throughout for consistency
and to improve readability
!
Table 1: Removed Day -21 to Day -7 window for some labs, and clarified that
screening labs should be obtained the same day as initial consent, when possible
!
Tables 1 and 3; Sections 8.6.2.3-8.6.2.11: Added a note for clarity that all assessments
should be performed predose, unless otherwise indicated
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Tables 1 and 3: 
 
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Tables 1, 2, 3, and 4 updated to include coagulation assessments with each safety lab 
visit
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Table 2: Renamed for clarity to include any participant who does not enter 
maintenance, and added “Survival Status/Subsequent Cancer Therapy” to the schedule 
of assessments. 
!
Tables 2 and 4: Clarified that the follow-up visit does not have to be a separate study 
visit; a phone call or other standard of care visit is acceptable 
!
Table 3: 
 
!
Table 8: Updated to match treatment windows in schedule of activities and to add 
windows to treatment
!
Table 9: Updated to add treatment windows
!
Table 15: Removed wording ‘which may have immune-modulating effect’ from 
‘Herbal and natural remedies’ prohibited medications.
!
Table 17: Footnote C inconsistencies corrected, additional footnotes added for clarity, 
and Carbon Dioxide added
!
Table 18: White Blood Cell Differential tests defined for clarity
!
Table 19: Added required test for urine microscopy for clarity
!
Sections 1.2 and 8.6.2.2; Table 3: 
 
!
Added new Section 2.2.3 providing further rationale for the combination of AZD2811 
and durvalumab
!
Section 5.2, Exclusion #3: Clarified that culinary use of turmeric and curry is 
acceptable. 
!
Section 5.2, Exclusion #12: Clarified that if COVID-19 test is performed, the results 
should be reported
!
Section 6.5: Added antibiotics taken within 90 days of Cycle 1 Day 1 will be recorded 
in the CRF
!
Section 7.1.1: Moved criteria “only applies if no other anticancer therapy” as inclusion 
number 5, from paragraph below, for clarity.
!
Appendices E1, E3, and E8: Language updated to remove references to central safety 
labs, as this study is using local labs only for safety assessments. 
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Section 8.2.3: Clarification that sites may also report Bazett’s Correction Formula 
(QTcB) if that is the local standard.
!
Section 8.3.10 and Appendix B2: Updated “congenital abnormality” to “congenital 
anomaly” to align with new company standards 
!
Section 8.8.1: Language added to allow for use of paper back up for ePRO
!
Section 9.4.2.3: Language clarified around missed RECIST assessments.
Version 5, 01 April 2021 (Amendment 4) – Italy Only
!
Tables 2 and 4 updated to include additional pregnancy testing through 90 days post 
last dose
!
Submitted as part of response to AIFA, and not submitted to any other Health 
Authority
Version 4, 23 February 2021 (Amendment 3) – Canada Only
!
Section 5.2, Exclusion #1 language clarified to exclude history of immune mediated 
reactions like pneumonitis
!
Section 5.2, Exclusion #8 language clarified to include pneumonitis as a type of 
interstitial lung disease
!
Sections 4.1.1 Table 8, 4.1.2 Table 9, and 6.6.1 Table 16: Clarified observation time 
between infusions is elapsed time from the end of the first infusion to the start of the 
next infusion (or in maintenance the observation time after the end of durvalumab at 
the site)
!
Submitted as part of response to Health Canada, and not submitted to any other Health 
Authority
Version 3, 04 November 2020 (Amendment 2)
!
Section 5.1, Inclusion #2 language updated to “T3 or T4 tumor stage”
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Section 5.1, Inclusion #3 
 
!
Section 5.2, Exclusion #18 was updated to clarify that this exclusion would not apply 
participants meeting re-treatment after relapse criteria
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Section 5.4 was updated to clarify that the maximum duration for rescreening, which 
must be complete within 7 weeks of initial consent
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Section 6.1.1 was updated to clarify that participants must be eligible to receive both 
durvalumab and AZD2811 to enter the maintenance phase 
!
Section 6.5 
 
!
Section 8.2.4 moved language from 8.5.1 regarding holds due to ANC and platelet 
counts, also clarifying that Day 1 treatment may be delayed up to 14 days for a 
maximum cycle length of 35 days
!
Section 8.5.1 was updated to clarify that Day 1 of a cycle may be delayed up to 
 
days, for a maximum cycle length of 
. It was also updated to clarify that the 
cycles are calibrated to have Day 1 always be the day that the patient received study 
treatment. Additionally, toxicity resolution language was updated state that toxicities 
should be resolved to Grade 1 or baseline for consistency
!
Section 8.6.2.1 
 
!
Appendix A5 was updated to change the SRC Chair from the International 
Coordinating Investigator to the Study Physician 
!
Updated randomized vs. enrolled vs. assigned to treatment language for clarity and 
consistency throughout 
!
Administrative changes for clarity and consistency throughout 
Version 2, 02 November 2020 (Amendment 1) - United States Only
!
Section 4.1.3 (DLT criteria) was updated to include Grade 4 anemia and any febrile 
neutropenia as DLTs
!
Section 5.2 (Exclusion Criteria) was updated to clarify that prophylactic cranial 
irradiation (PCI) is allowed but must be completed before first dose of study 
medication
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Sections 5.2 (Exclusion Criteria) and 6.5.2.1 (Prohibited Concomitant Medication for 
AZD2811) were updated to exclude clinical inhibitors of BCRP during the safety run-
in
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Section 8.5.2 (Specific Toxicity Management and Dose Modification Information -
Durvalumab) was updated to specifically indicate that, in the US, dose modifications 
for durvalumab should be consistent with recommendations in the USPI.
Version 1, 01 September 2020 (Original Protocol)
Initial creation

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TABLE OF CONTENTS
TITLE PAGE........................................................................................................................ 1
VERSION HISTORY ........................................................................................................... 3
TABLE OF CONTENTS .................................................................................................... 12
1
PROTOCOL SUMMARY ................................................................................ 20
1.1
Synopsis ........................................................................................................... 20
1.2
Schema............................................................................................................. 24
1.3
Schedule of Activities ....................................................................................... 25
2
INTRODUCTION............................................................................................ 44
2.1
Study Rationale ................................................................................................ 44
2.2
Background ...................................................................................................... 44
2.2.1
AZD2811.......................................................................................................... 45
2.2.2
Durvalumab...................................................................................................... 45
2.2.3
Rationale for Combination of AZD2811 and durvalumab in 1L ES-SCLC ........ 46
2.3
Benefit/Risk Assessment................................................................................... 51
2.3.1
Risk Assessment ............................................................................................... 51
2.3.2
Benefit Assessment........................................................................................... 54
2.3.3
Overall Benefit: Risk Conclusion...................................................................... 54
3
OBJECTIVES AND ENDPOINTS................................................................... 56
4
STUDY DESIGN ............................................................................................. 60
4.1
Overall Design.................................................................................................. 60
4.1.1
Induction Phase ................................................................................................ 61
4.1.2
Maintenance Phase ........................................................................................... 62
4.1.2.1
Maintenance Phase Overview ........................................................................... 62
4.1.2.2
Safety Run-In ................................................................................................... 63
4.1.3
DLT Criteria ..................................................................................................... 65
4.1.4
Definition of DLT-Evaluable Participants.......................................................... 66
4.1.5
Study Conduct Mitigation During Study Disruptions Due to Cases of Civil 
Crisis, Natural Disaster, or Public Health Crisis ................................................ 66
4.2
Scientific Rationale for Study Design ............................................................... 67
4.2.1
Rationale for 
 of Induction Therapy..................................................... 67
4.2.2
Rationale for AZD2811 and Durvalumab Maintenance Therapy........................ 67
4.3
Justification for Dose........................................................................................ 68
4.3.1
Rationale for Dose of Platinum-based Chemotherapy ....................................... 68
4.3.2
Rationale for Dose of AZD2811........................................................................ 68
4.3.3
Rationale for Dose of Durvalumab.................................................................... 69
4.4
End of Study Definition.................................................................................... 69
5
STUDY POPULATION.................................................................................... 71
5.1
Induction Phase Inclusion Criteria..................................................................... 71
5.2
Induction Phase Exclusion Criteria ................................................................... 72
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5.3
Maintenance Phase Eligbility Criteria ............................................................... 75
5.3.1
Maintenance Phase Inclusion Criteria ............................................................... 75
5.3.2
Maintenance Phase Exclusion Criteria .............................................................. 76
5.4
Lifestyle Considerations ................................................................................... 76
5.5
Screen Failures ................................................................................................. 77
6
STUDY INTERVENTION ............................................................................... 78
6.1
Study Intervention(s) Administered................................................................... 78
6.1.1
Investigational Products.................................................................................... 78
6.1.2
Non-investigational Products............................................................................ 79
6.1.3
Duration of Treatment and Criteria for Treatment After Initial Assessment of PD
......................................................................................................................... 80
6.2
Preparation/Handling/Storage/Accountability ................................................... 81
6.2.1
AZD2811.......................................................................................................... 82
6.2.2
Durvalumab...................................................................................................... 82
6.2.3
Standard of Care: EP......................................................................................... 82
6.2.4
G-CSF .............................................................................................................. 83
6.3
Measures to Minimize Bias: Randomization and Blinding ................................ 83
6.4
Study Intervention Compliance......................................................................... 83
6.5
Concomitant Therapy........................................................................................ 83
6.5.1
Permitted Concomitant Medication................................................................... 84
6.5.1.1
Permitted Concomitant Medication for AZD2811 ............................................. 84
6.5.1.2
Permitted Concomitant Medication for Durvalumab ......................................... 84
6.5.2
Prohibited Concomitant Medication and Treatments ......................................... 85
6.5.2.1
Prohibited Concomitant Medication for AZD2811 ............................................ 85
6.5.2.2
Prohibited Concomitant Medication and Treatments for Durvalumab................ 86
6.5.3
Drug-drug Interactions...................................................................................... 88
6.5.3.1
AZD2811 Drug-drug Interactions ..................................................................... 88
6.5.3.2
Durvalumab Drug-drug Interactions.................................................................. 88
6.5.4
Rescue Medicine............................................................................................... 88
6.6
Dose Modification ............................................................................................ 89
6.6.1
Dose Modification for AZD2811....................................................................... 89
6.6.2
Dose Modification for Durvalumab................................................................... 90
6.6.3
Dose Modification of Platinum-based Chemotherapy, Cisplatin, and/or 
Carboplatin....................................................................................................... 90
6.7
Intervention After the End of the Study............................................................. 90
7
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL........................................................... 90
7.1
Discontinuation of Study Intervention............................................................... 90
7.1.1
Re-treatment Following Relapse ....................................................................... 91
7.2
Participant Withdrawal from the Study.............................................................. 92
7.3
Lost to Follow-up ............................................................................................. 92
8
STUDY ASSESSMENTS AND PROCEDURES.............................................. 93

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8.1
Efficacy Assessments........................................................................................ 94
8.1.1
Reading of Scans .............................................................................................. 96
8.1.2
Survival Assessments........................................................................................ 96
8.2
Safety Assessments........................................................................................... 96
8.2.1
Physical Examinations...................................................................................... 97
8.2.2
Vital Signs ........................................................................................................ 97
8.2.3
Electrocardiograms ........................................................................................... 97
8.2.4
Clinical Safety Laboratory Assessments............................................................ 98
8.2.5
Early Participant Review for Safety ................................................................ 101
8.2.6
WHO ECOG Performance Status.................................................................... 101
8.2.7
Other Safety Assessments ............................................................................... 101
8.3
Adverse Events and Serious Adverse Events................................................... 102
8.3.1
Time Period and Frequency for Collecting AE and SAE Information.............. 102
8.3.2
Follow-up of AEs and SAEs ........................................................................... 103
8.3.3
Causality Collection........................................................................................ 103
8.3.4
Adverse Events Based on Signs and Symptoms .............................................. 104
8.3.5
Adverse Events Based on Examinations and Tests .......................................... 104
8.3.6
Hy’s Law........................................................................................................ 104
8.3.7
Disease Progression........................................................................................ 105
8.3.8
Disease Under Study....................................................................................... 105
8.3.9
Reporting of Serious Adverse Events .............................................................. 105
8.3.10
Pregnancy....................................................................................................... 106
8.3.10.1
Maternal Exposure.......................................................................................... 106
8.3.10.2
Paternal Exposure........................................................................................... 106
8.3.11
Medication Error............................................................................................. 107
8.3.12
Adverse Events of Special Interest.................................................................. 107
8.3.12.1
AESIs for AZD2811 ....................................................................................... 107
8.3.12.2
AESIs for Durvalumab ................................................................................... 107
8.4
Overdose ........................................................................................................ 108
8.5
Management of Study Intervention-related Toxicities ..................................... 109
8.5.1
Specific Toxicity Management and Dose Modification Information – AZD2811
....................................................................................................................... 109
8.5.2
Specific Toxicity Management and Dose Modification Information –
Durvalumab.................................................................................................... 113
8.6
Human Biological Samples............................................................................. 114
8.6.1
Pharmacokinetics............................................................................................ 115
8.6.1.1
Determination of Drug Concentration ............................................................. 115
8.6.2
116
8.6.2.1
116
8.6.2.2
. 117
8.6.2.3
118
8.6.2.4
119
8.6.2.5
119
8.6.2.6
 
119
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8.6.2.7
 
120
8.6.2.8
121
8.6.2.9
121
8.6.2.10
122
8.6.2.11
122
8.7
123
8.8
Other Assessments.......................................................................................... 123
8.8.1
Patient-reported Outcomes.............................................................................. 123
8.8.1.1
EORTC QLQ-C30 .......................................................................................... 123
8.8.1.2
EORTC QLQ-LC13........................................................................................ 124
8.8.2
Administration of the Patient-reported Outcome Questionnaires ..................... 124
9
STATISTICAL CONSIDERATIONS.............................................................. 125
9.1
Of note, no interim analyses, primary analysis or exploratory external controls 
analysis will be carried out and the study will proceed to final analysis, based 
upon which the abbreviated CSR will be written. As a result of the early 
termination, the DCO for the final analysis in this study is planned for 18 June 
2022.Statistical Hypotheses ............................................................................ 125
9.2
Sample Size Determination............................................................................. 125
9.3
Populations for Analyses................................................................................. 127
9.4
Statistical Analyses ......................................................................................... 127
9.4.1
General Considerations................................................................................... 127
9.4.2
Efficacy .......................................................................................................... 129
9.4.2.1
Primary Endpoint(s)........................................................................................ 130
9.4.2.2
Secondary Endpoints ...................................................................................... 130
9.4.2.3
Exploratory Endpoint(s).................................................................................. 130
9.4.3
Patient-reported outcomes............................................................................... 133
9.4.3.1
EORTC QLQ-C30 .......................................................................................... 134
9.4.3.2
EORTC QLQ-LC13........................................................................................ 134
9.4.4
Safety ............................................................................................................. 134
9.4.4.1
Other Safety Endpoint(s) ................................................................................ 137
9.4.5
Other Analyses................................................................................................ 137
9.4.6
137
9.4.7
Pharmacokinetic Analyses .............................................................................. 137
9.5
Interim Analyses............................................................................................. 138
9.6
Data Monitoring Committee ........................................................................... 139
10
SUPPORTING 
DOCUMENTATION 
AND 
OPERATIONAL
CONSIDERATIONS ...................................................................................... 139
11
REFERENCES............................................................................................... 190
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2015;373(1):23-34.......................................................................................... 191
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1995;13(5):1215-20. ....................................................................................... 191
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B-CLL resistance to NK cell cytotoxicity can be overcome in vitro and in vivo 
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ipilimumab in advanced melanoma. N Engl J Med. 2013;369:122-33. ............ 192
LIST OF FIGURES
Figure 1
Study Design ........................................................................................... 24
Figure 2
 
..................................................................................... 48
Figure 3
 
........................................................................................... 49
Figure 4
 
........................................................................................................ 49
Figure 5
 
......................... 50
Figure 6
 
................................................................. 50
LIST OF TABLES
Table 1
Schedule of Activities for the Induction Period........................................ 25
Table 2
Schedule of Activities for the End of Treatment Period for Participants 
Who Do Not Enter the Maintenance Phase............................................... 32
Table 3
Schedule of Activities for the Maintenance Period................................... 33
Table 4
Schedule of Activities for the End of Treatment Period for Participants 
Entering the Maintenance Phase and Re-Treatment After Relapse 
Participants.............................................................................................. 38
Table 5
Schedule of Activities for Re-treatment after Relapse .............................. 41
Table 6
Risk Assessment...................................................................................... 51
Table 7
Objectives and Endpoints......................................................................... 56
Table 8
Study Intervention During the Induction Phase ........................................ 61
Table 9
Study Intervention During the Maintenance Phase ................................... 62
Table 10
Highly effective methods of contraception (< 1% failure rate) ................. 77
Table 11
Study Interventions.................................................................................. 78
Table 12
List of Investigational Study Interventions............................................... 79
Table 13
Non-Investigational Medicinal Products for this Study ............................ 80
Table 14
Supportive medications for durvalumab................................................... 85
Table 15
Prohibited concomitant medications for durvalumab................................ 87
Table 16
Dose Modification for AZD2811 ............................................................. 89
Table 17
Clinical Chemistry................................................................................... 99
Table 18
Hematology............................................................................................. 99
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Table 19
Urinalysis .............................................................................................. 100
Table 20
Other Safety Tests ................................................................................. 100
Table 21
Dose Modification for Non-skin Toxicity .............................................. 111
Table 22
Dose Modification for Skin Toxicity...................................................... 113
Table 23
Populations for Analysis ........................................................................ 127
Table 24
Summary of Methods of Assessment ..................................................... 165
Table 25
Evaluation of Target Lesions ................................................................. 170
Table 26
Evaluation of Non-target Lesions........................................................... 171
Table 27
Overall Visit Response .......................................................................... 172
LIST OF APPENDICES
Appendix A
Regulatory, Ethical, and Study Oversight Considerations....................... 140
Appendix B
Adverse Events: Definitions and Procedures for Recording, Evaluating, 
Follow-up, and Reporting ...................................................................... 146
Appendix C
Handling of Human Biological Samples ................................................ 151
Appendix D
..................................................... 153
Appendix E
Actions Required in Cases of Increases in Liver Biochemistry and 
Evaluation of Hy’s Law......................................................................... 156
Appendix F
Guidelines for Evaluation of Objective Tumor Response Using RECIST 
v1.1 Criteria (Response Evaluation Criteria in Solid Tumors)................ 163
Appendix G
Patient-Reported Outcomes: EORTC QLQ-C30, EORTC QLQ-LC13... 177
Appendix H
Changes Related to Mitigation of Study Disruptions Due to Cases of 
Civil Crisis, Natural Disaster, or Public Health Crisis ............................ 181
Appendix I
Abbreviations ........................................................................................ 186
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1
PROTOCOL SUMMARY
1.1
Synopsis
Protocol Title: A Phase II, multicenter, open-label, single arm study to determine the 
efficacy, safety, and tolerability of AZD2811 and durvalumab combination as maintenance 
therapy after induction with platinum-based chemotherapy combined with durvalumab, for the 
first-line treatment of patients with extensive stage small-cell lung cancer.   
Short Title: Phase II maintenance study of AZD2811 + durvalumab in ES-SCLC.
On 14 December 2021, AstraZeneca took the decision to terminate enrolment for this study 
prior to completion due to the evolving benefit risk profile of AZD2811 that does not support 
further development for the first-line treatment of patients with extensive stage small-cell lung 
cancer. Patients already enrolled in the study were able to continue. However, no further 
patients were permitted to start AZD2811 treatment and ongoing patients transitioning into the 
maintenance phase after this date were offered durvalumab monotherapy. As a result of the 
early termination, the data cut-off for the final analysis in this study is planned for 18 June 
2022. 
Sections from CSP v8.0 are retained throughout this protocol for reference. Clinical Study 
Protocol v8.0 was prepared to include urgent safety measures via a Dear Investigator Letter; 
however, CSP V 8.0 was not implemented due to early termination. Clinical Study Protocol 
v8.0 is superseded by CSP v9.0.
Rationale: Despite improved efficacy in the treatment of extensive stage small-cell lung 
cancer (ES-SCLC) resulting from the addition of programmed cell death-ligand 1 
immunotherapy to platinum-etoposide, there remains an urgent need for therapies that prolong 
progression-free survival and overall survival in this disease. Preliminary clinical data suggest 
that AZD2811 may be effective in stabilizing disease in later line SCLC patients. This trial 
will investigate whether a similar benefit can be demonstrated in first line SCLC patients 
treated with AZD2811 plus durvalumab maintenance therapy, following 
 of 
durvalumab plus platinum-etoposide induction therapy.
Objectives and Endpoints
Objectives
Endpoints
Primary
To evaluate the efficacy of AZD2811 + durvalumab 
by assessment of the proportion of participants alive 
and progression free at 12 months (APF12) who 
have not progressed during etoposide and platinum-
based chemotherapy (EP)-durvalumab based 
induction therapy.
The proportion of participants APF12 will be defined as 
the Kaplan-Meier estimate of progression-free survival 
(PFS) per Response Evaluation Criteria in Solid Tumors 
(RECIST) v1.1 as assessed by the investigator at local site 
at 12 months, in participants who enter the maintenance 
phase. 
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Objectives
Endpoints
Secondary
To evaluate efficacy of AZD2811 + durvalumab by 
assessment of the proportion of participants alive at 
12 months (OS12), 15 months (OS15), and 18 
months (OS18), who have not progressed during EP-
durvalumab based induction therapy.
The proportion of participants OS12, OS15, and OS18 will 
be defined as the Kaplan-Meier estimate of overall 
survival (OS) at 12 months, 15 months, and 18 months, 
respectively, in participants who enter the maintenance 
phase.
To evaluate efficacy of AZD2811 + durvalumab by 
assessment of the proportion of participants alive and 
progression free at 6 months (APF6) and 9 months 
(APF9) who have not progressed during EP-
durvalumab based induction therapy.
The proportion of participants alive and progression free at 
APF6 and APF9 will be defined as the Kaplan-Meier 
estimate of PFS per RECIST v1.1 as assessed by the 
investigator at local site at 6 months and 9 months, 
respectively, in participants who enter the maintenance 
phase.
To evaluate efficacy of EP-durvalumab by 
assessment of objective response rate (ORR) in the 
induction phase. 
ORR is defined as the proportion of participants with 
measurable disease at baseline who have a confirmed 
complete response (CR) or partial response (PR), by the 
investigator at local site per RECIST v1.1 in the induction 
phase (all participants).
To evaluate efficacy of AZD2811 + durvalumab by 
assessment of ORR in the participants who had not 
progressed during EP-durvalumab based induction 
therapy. 
ORR is defined as the proportion of participants with 
measurable disease at baseline who have a confirmed CR 
or PR, by the investigator at local site per RECIST v1.1, in 
participants who enter the maintenance phase.
To evaluate efficacy of AZD2811 + durvalumab by 
assessment of PFS in participants who had not 
progressed during EP-durvalumab based induction 
therapy. 
PFS is defined as time from date of first dose study 
intervention in the induction phase until progression per 
RECIST v1.1 or death due to any cause. The median 
Kaplan-Meier estimate in participants who enter the 
maintenance phase.
To evaluate efficacy of AZD2811 + durvalumab by 
assessment of OS in participants who had not 
progressed during EP-durvalumab based induction 
therapy. 
OS is defined as time from date of first dose study 
intervention in the induction phase until the date of death 
due to any cause. The median Kaplan-Meier estimate in 
participants who enter the maintenance phase.
To assess the safety and tolerability profile of study 
intervention in small-cell lung cancer (SCLC).
Safety and tolerability will be evaluated in terms of 
adverse events, vital signs, physical examination, clinical 
chemistry, thyroid-stimulating hormone, prothrombin time
/partial prothrombin time /international normalized ratio, 
hematology, electrocardiograms, and urinalysis, as well as 
treatment delays, dose reductions, and dose 
discontinuations.
To evaluate the pharmacokinetics of durvalumab and 
AZD2811.
Concentration of durvalumab, and AZD2811 and its 
metabolite in serum and whole blood, respectively. 
To evaluate the effect of AZD2811 + durvalumab on 
SCLC symptoms and health-related quality of life 
(QoL) using European Organization for Research 
and Treatment of Cancer (EORTC) 30-item Core 
Quality of Life Questionnaire (QLQ-C30) and 13-
EORTC QLQ-C30: Symptoms (fatigue, pain, 
nausea/vomiting, dyspnea, loss of appetite, insomnia, 
constipation, and diarrhea). Health-related 
QoL/functioning (physical function, role function, 
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Objectives
Endpoints
item Lung Cancer Quality of Life Questionnaire
(QLQ-LC13).
and global health status/QoL).
EORTC QLQ-LC13: Disease-related symptoms (dyspnea, 
cough, hemoptysis, chest pain, arm/shoulder pain, and 
other pain).
For Exploratory objectives and endpoints, see Section 3. 
Overall Design
This is a Phase II, multicenter, open-label, single arm study in ES-SCLC treatment naïve 
patients who do not progress per Response Evaluation Criteria in Solid Tumors (RECIST) 
v1.1 after induction with etoposide and platinum-based chemotherapy-durvalumab. 
Participants will be treated for 
 on an every
 schedule in an induction 
phase with platinum-based induction therapy (cisplatin or carboplatin plus etoposide) + 
durvalumab. At the end of this induction period, participants will be assessed for disease 
progression, per RECIST v1.1. 
Participants who have not progressed per RECIST v1.1 at the end of the induction phase will 
continue into the maintenance phase of the trial following confirmation of maintenance phase 
eligibility criteria.  
The maintenance phase will commence with a safety run-in period, in which approximately 
six participants will be followed for (at least) one cycle, to assess safety of the AZD2811 + 
durvalumab combination in order to provide the earliest opportunity to assess tolerability of 
the combination in those approximately six participants. After the completion of ≥
 
(≥1 cycle) dosing in the first 6 evaluable participants, all safety data (including, but not 
limited to, dose-limiting toxicities, adverse events of special interest, laboratory safety 
assessment, vital signs, and physical examination), will be assessed to judge if the 
combination is safe and tolerable. This assessment, and subsequent recommendation to 
continue dosing in the maintenance phase, will be undertaken by a Safety Review Committee 
(SRC). Participants will be treated with AZD2811 + durvalumab as maintenance therapy until 
confirmed progressive disease, start of non-protocol defined anticancer therapy, unacceptable 
toxicity, or withdrawal of consent.
Disclosure Statement: This is an open-label treatment, single arm study.
Number of Participants:
Approximately 100 participants will be assigned to treatment to achieve 80 evaluable 
participants having received maintenance therapy.
From Clinical Study Protocol (CSP) v8.0 onwards, the starting dose of AZD2811 in the 
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maintenance phase will be 
, the study will seek to achieve 80 evaluable participants on 
that starting dose.
Note: “Enrolled” means a participant’s, or their legally acceptable representative’s, agreement 
to participate in a clinical study following completion of the informed consent process. 
Potential participants who are screened for the purpose of determining eligibility for the study, 
but are not assigned in the study, are considered “screen failures”, unless otherwise specified 
by the protocol. “Assigned” means that a participant has completed the screening period and 
has received at least one dose of study treatment.
Intervention Groups and Duration: A single group of participants will be treated as 
follows:
!
Screening: Days -21 to Day -1
!
Induction Phase: 
 to 
∀
Durvalumab 
∀
Carboplatin (area under the curve 5 to 6) or cisplatin (75 to 80 mg/m2) 
∀
Etoposide (80 to 100 mg/m2) on 
!
Maintenance Phase: 
 to confirmed disease progression
∀
AZD2811 (
 with mandatory granulocyte colony stimulating 
factor on/from 
∀
Durvalumab (
)
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Data Monitoring Committee: A SRC will be used to assess the participants in the safety 
run-in.
Statistical Methods: The study is single arm so there will be no formal statistical hypotheses. 
The analysis for the study will be descriptive.
1.2
Schema
Figure 1
Study Design
C = cycle; D = day; ES-SCLC = extensive stage small-cell lung cancer; PD = progressive disease; 
PS = performance status; RECIST = Response Evaluation Criteria in Solid Tumors.
 
 
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1.3
Schedule of Activities
Table 1
Schedule of Activities for the Induction Period
Screeninga
During Induction Chemotherapy
1 cycle =
Notes
Details in 
CSP 
Section or 
Appendix
C1
C1
C1
C1
C2
C2
C2
C2
C3
C3
C3
C3
C4
C4
C4
C4
Week
Day
-21 to -1
Window (days) 
unless a dose 
delay is needed 
for toxicity 
management
NA
± 3
± 3
± 3
± 3
± 3
± 3
± 3
Informed consent 
X
Appendix 
A 3
Eligibility criteria
X
X
Section 
5.1 and 
5.2
Maintenance 
eligibility check
X
Confirm participant does not 
have progressive disease on 
C4 scan
Physical 
examination (full)
X
Section 
8.2.1
Targeted physical 
examination 
(based on 
symptoms)
X
X
X
X
Skin must be assessed at 
each visit regardless of 
changes
Section 
8.2.1
Vital signs 
X
Xb
X
X
X
X
X
X
X
Section 
8.2.2
Triplicate 12-lead 
ECG
X
As clinically indicated
Section 
8.2.3
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Table 1
Schedule of Activities for the Induction Period
Screeninga
During Induction Chemotherapy
1 cycle = 
Notes
Details in 
CSP 
Section or 
Appendix
C1
C1
C1
C1
C2
C2
C2
C2
C3
C3
C3
C3
C4
C4
C4
C4
Concomitant 
medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Section 
6.5
Section 
6.5
Medical history 
and demography, 
including baseline 
characteristics, 
and tobacco 
history
X
Collecting smoking pack-
years
Section 
8.2
Clinical 
chemistryb, c
X
Xb
X
X
X
X
X
X
X
Results for urea and 
electrolytes, and liver 
function tests must be 
available before commencing 
an infusion 
Section 
8.2.4
Hematology b, c
X
Xb
X
X
X
X
X
X
X
Results for full blood count 
must be available before 
commencing an infusion 
Section 
8.2.4
Fibrinogen and 
CRP
X
X
Section 
8.2.4
TSH, free T3, and 
free T4
X
Xb
X
X
X
Section 
8.2.4
PT/PTT/INR b, c
X
Xb
X
X
X
X
X
X
X
Section 
8.2.4
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Table 1
Schedule of Activities for the Induction Period
Screeninga
During Induction Chemotherapy
1 cycle = 
Notes
Details in 
CSP 
Section or 
Appendix
C1
C1
C1
C1
C2
C2
C2
C2
C3
C3
C3
C3
C4
C4
C4
C4
Urinalysis b, c
X
Xb
X
X
X
Section 
8.2.4
spO2 assessment
X
As clinically indicated
X
If abnormal at any time 
during the study, to be 
repeated on Day 1 of 
subsequent cycles.
Section 
8.2.7
Hepatitis B and C 
and HIV
X
As clinically indicated
Section 
8.2.4
Tuberculosis Test
X
As clinically indicated
Section 
8.2.4
Pregnancy test
X
Xb
X
X
X
Section 
8.2.4
Tumor evaluation 
(CT or MRI) 
(RECIST 1.1) 
Chest /Abdomen 
X
X
X
Participant’s diagnostic scan 
may be used as a baseline 
scan if taken within 28 days 
of C1D1 and in accordance 
with the requirements 
outlined in Appendix F.
 
, for confirmation of 
maintenance eligibility.
Section 
8.1 and 
Appendix
F
Tumor evaluation 
(CT or MRI) 
(RECIST v1.1) 
Pelvis /Additional 
Anatomy (as 
X
X
X
Performed at baseline and 
follow up assessments if 
appropriate based on signs 
and symptoms of the 
participant
Section 
8.1.1
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Table 1
Schedule of Activities for the Induction Period
Screeninga
During Induction Chemotherapy
1 cycle = 
Notes
Details in 
CSP 
Section or 
Appendix
C1
C1
C1
C1
C2
C2
C2
C2
C3
C3
C3
C3
C4
C4
C4
C4
clinically 
indicated)
ECOG 
performance 
status
X
X
X
X
X
X
Section 
8.2.6
AE/SAE 
Assessment
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Section 
8.3 and 
8.2.7
Durvalumab
Section 
4.1 and  
6.2.2  
Etoposide 
The immunotherapy agents 
are infused first followed by 
the etoposide (
) + 
cisplatin/carboplatin 
regimen.
Infuse over 0.5 to 1 hour.
Section 
4.1 and 
6.2.3
Carboplatin or 
cisplatin 
The immunotherapy agents 
are infused first followed by 
the etoposide + 
cisplatin/carboplatin (
) 
regimen.
If cisplatin, infuse over 1 to 2 
hours. If carboplatin, infuse 
over 0.5 to 1 hour.
Section 
4.1 and 
6.2.3
EORTC QLQ-
C30 v3, EORTC 
QLQ-LC13
X
X
X
X
X
PRO should be collected 
prior to any other visit 
procedures to avoid bias in 
the event of PD
Section 
8.8.1
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Table 1
Schedule of Activities for the Induction Period
Screeninga
During Induction Chemotherapy
1 cycle = 
Notes
Details in 
CSP 
Section or 
Appendix
C1
C1
C1
C1
C2
C2
C2
C2
C3
C3
C3
C3
C4
C4
C4
C4
Section 
8.7; 
Appendix
D
Section 
8.6.2.1
Section 
8.6.2.2
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Table 1
Schedule of Activities for the Induction Period
Screeninga
During Induction Chemotherapy
1 cycle = 
Notes
Details in 
CSP 
Section or 
Appendix
C1
C1
C1
C1
C2
C2
C2
C2
C3
C3
C3
C3
C4
C4
C4
C4
Section 
8.6.2.3
Section 
8.6.2.4
Section 
8.6.2.5
Section 
8.6.2.6
Section 
8.6.2.7
Section 
8.6.2.8
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Table 1
Schedule of Activities for the Induction Period
Screeninga
During Induction Chemotherapy
1 cycle = 
Notes
Details in 
CSP 
Section or 
Appendix
C1
C1
C1
C1
C2
C2
C2
C2
C3
C3
C3
C3
C4
C4
C4
C4
Section 
8.6.2.9
Section 
8.6.2.10
Section 
8.6.2.11
AE = Adverse event; C = Cycle; 
; CRP = C-reactive protein; CSP = Clinical study protocol; CT = Computed tomography; 
 
; D = Day; 
; ECG = Electrocardiogram; ECOG = Eastern Cooperative Oncology Group; 
EORTC = European Organization for Research and Treatment of Cancer; HIV  = Human immunodeficiency virus; INR = International normalized ratio; IV = Intravenous; MRI = 
Magnetic resonance imaging; NA = not applicable; 
; PD = Progressive disease; PRO = Patient-reported outcomes; PT = prothrombin 
time; PTT = partial prothrombin time; QLQ C30 v3 = 30 item Core Quality of Life Questionnaire, version 3; QLQ-LC13 = 13-item Lung Cancer Quality of Life Questionnaire; 
RECIST 1.1 = Response Evaluation Criteria in Solid Tumors, version 1.1; SAE = Serious adverse event; SpO2 = Saturation of peripheral oxygen; T3 = Triiodothyronine; 
T4 = Thyroxine; TSH = Thyroid-stimulating hormone.
a
Screening procedures should be performed on the same day as consent, when possible, including 
 and PRO.  
b
Assessments do not need to repeated on C1D1 if within 3 days of screening assessment.
c
Assessments do not need to be repeated on Day 1 of a cycle if performed within 3 days of the visit.
All assessments, including exploratory and safety labs, must be performed pre-dose, unless otherwise specified. 
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Table 2
Schedule of Activities for the End of Treatment Period for Participants Who Do Not Enter the Maintenance 
Phase
Procedure
Disease 
Progression
EOT
FU
(90 days
+/-1 week 
after last 
dose)
Every 2 
months+/
- 1 week 
following 
FU
Notes
Details in 
CSP Section 
or Appendix
Vital signs
X
Section 8.2.2
Physical examination
X
X
Section 8.2.1
ECOG performance status
X
Section 8.2.6
Concomitant medications
X
X
X
Participant to return 
/EOT
Section 6.5
AE/SAE assessment
X
X
X
X
Participants should be asked about any skin changes or rashes at each visit.
Section 8.3
Single 12-lead ECG
X
Section 8.2.3
Hematology
X
Section 8.2.4
Clinical chemistry
X
Section 8.2.4
PT/PTT/INR
X
Section 8.2.4
Fibrinogen and CRP
X
Section 8.2.4
Pregnancy test 
X
X
In women of childbearing potential only.
Pregnancy testing will be performed monthly (28 days +/- 7 days) through 
90 days post last dose or until a new treatment is initiated, whichever is 
shorter.
The pregnancy testing can be performed at a standard of care visit, and 
does not require a separate study visit.
Section 8.2.4
Survival Status/subsequent 
cancer therapy
X
A separate study visit is not required. Data from a standard of care visit or 
a phone call may be used. 
Section 8.1.2
AE = Adverse event; CRP = C-reactive protein; CSP = Clinical study protocol; ECG = Electrocardiogram; ECOG = Eastern Cooperative Oncology Group; EOT = End of 
treatment; FU = Follow-up; INR = International normalized ratio; PT = prothrombin time; PTT = partial prothrombin time; SAE = Serious adverse event.
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Table 3
Schedule of Activities for the Maintenance Period
Procedure
During Maintenance Phase a
(1 cycle = 
)
Notes
Details in 
CSP 
Section 
or 
Appendix
Cycle 5
(cycle = 
Cycle 6
Cycle 7
and beyond
Window (days) unless a 
dose delay is needed for 
toxicity management
± 1
± 2
± 1
± 2
± 1
± 2
Eligibility Criteria
X
Must be confirmed prior to dosing with 
AZD2811
Section 
5.3
Physical examination 
(full)
X
X
X
Skin should be examined at each visit regardless 
of changes 
Section 
8.2.1
Vital signs
X
X 
X
X
X
X
X
X
Day 12 assessments are mandatory for Cycles 5 
and 6; additional Day 12 visits may be conducted 
at the discretion of the Investigator.
Section 
8.2.2
ECOG performance status
X
X
X
Section 
8.2.6
Concomitant medications
X
X
X
X
X
X
X
Day 2 
OR Day 
3
X
X
X
X
X
X
Section 
6.5
Section 
6.5
AE/SAE assessment 
X
X
X
X
X
X
X
Day 2 
OR Day 
3
X
X
X
X
X
X
Section 
8.3 and 
8.2.7
Triplicate 12-lead ECGs
X
As clinically indicated
Section 
8.2.3
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Table 3
Schedule of Activities for the Maintenance Period
Procedure
During Maintenance Phase a
(1 cycle = 
)
Notes
Details in 
CSP 
Section 
or 
Appendix
Cycle 5
(cycle = 
)
Cycle 6
Cycle 7
and beyond
Window (days) unless a 
dose delay is needed for 
toxicity management
± 1
± 2
± 1
± 2
± 1
± 2
Hematology
X
X
X
X
X
X
X
X
X
Day 12 assessments are mandatory for Cycles 5 
and 6; additional Day 12 visits may be conducted 
at the discretion of the Investigator.
Section 
8.2.4
Clinical chemistry
X
X
X
X
X
X
X
Section 
8.2.4
Urinalysis
X
X
X
Section 
8.2.4
spO2 assessment
X
As clinically indicated
To be collected if clinically indicated and at the 
end of therapy. If abnormal, to be repeated on 
Day 1 of subsequent cycles.
Section 
8.2.7
PT/PTT/INR
X
X
X
X
X
X
X
Section 
8.2.4
Fibrinogen and CRP
X
X
X
Section 
8.2.4
TSH, free T3, and free T4
X
X
X
Section 
8.2.4
Pregnancy test 
X
X
X
Section 
8.2.4
EORTC QLQ-C30 v3, 
EORTC QLQ-LC13
X
X
Day 1 of every 
other cycle, 
starting with cycle 
8
PRO should be collected prior to any other visit 
procedures to avoid bias in the event of PD 
Section 
8.8.1
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Table 3
Schedule of Activities for the Maintenance Period
Procedure
During Maintenance Phase a
(1 cycle = 
)
Notes
Details in 
CSP 
Section 
or 
Appendix
Cycle 5
(cycle = 
Cycle 6
Cycle 7
and beyond
Window (days) unless a 
dose delay is needed for 
toxicity management
± 1
± 2
± 1
± 2
± 1
± 2
Blood sample for 
AZD2811 PK (Predose)
X
X
Section 
8.6.1
Blood sample for 
AZD2811 PK (Postdose)
X
X
X
X
X
X
X 
X
X
Day 1 and Day 8 
of Cycles 7 and 8 
only
PK blood samples will be collected from all 
participants 2 hours (± 15 minute from the start 
of infusion for each time point) 
Section 
8.6.1
Blood sample for 
durvalumab PK (Predose)
X
X
Day 1 of Cycle 7 
only
Section 
8.6.1
Section 
8.6.2.2
Section 
8.6.2.3
Section 
8.6.2.4
Section 
8.6.2.5
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Table 3
Schedule of Activities for the Maintenance Period
Procedure
During Maintenance Phase a
(1 cycle = 
)
Notes
Details in 
CSP 
Section 
or 
Appendix
Cycle 5
(cycle = 
)
Cycle 6
Cycle 7
and beyond
Window (days) unless a 
dose delay is needed for 
toxicity management
± 1
± 2
± 1
± 2
± 1
± 2
Section 
8.6.2.6
Section 
8.6.2.7
Section 
8.6.2.8
Section 
8.6.2.9
Section 
8.6.2.10
Section 
8.6.2.11
CT Scan or MRI 
Chest/Abdomen
RECIST v1.1 tumor assessments should be performed at W18, 24, 30 and 36 ± 1 week and 
every 8 weeks ± 1 week thereafter.  The weeks are referenced to the first dose of study 
intervention in the induction phase.
Where possible, every effort should be made to 
schedule the scan within 1 week prior to dosing 
with AZD2811; scan results MUST be reviewed
prior to dosing to confirm the absence of disease 
progression.  
Section 
8.1
CT Scan or MRI Pelvis 
/Additional Anatomy
As clinically indicated
Section 
8.1.1
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Table 3
Schedule of Activities for the Maintenance Period
Procedure
During Maintenance Phase a
(1 cycle = 
)
Notes
Details in 
CSP 
Section 
or 
Appendix
Cycle 5
(cycle = 
)
Cycle 6
Cycle 7
and beyond
Window (days) unless a 
dose delay is needed for 
toxicity management
± 1
± 2
± 1
± 2
± 1
± 2
Durvalumab 
administration
Section 
4.1 and 
6.2.2
AZD2811 administration
Section 
4.1 and 
6.2.1
G-CSF
Section 
6.2.4
AE = Adverse event; ANC = absolute neutrophil count; C = Cycle; CBCs = complete blood counts; 
; CRP = C-reactive protein; 
CSP = Clinical study protocol; CT = Computed tomography; 
 D = Day; 
 
ECG = Electrocardiogram; ECOG = Eastern Cooperative Oncology Group; EORTC = European Organization for Research and Treatment of Cancer; EOT = end of treatment; 
G-CSF = granulocyte colony stimulating factor; INR = international normalized ratio; IV = Intravenous; MRI = Magnetic resonance imaging; 
 
; PD = Progressive disease; PK = Pharmacokinetic(s); PRO = Patient-reported outcomes; PT = prothrombin time; PTT = partial prothrombin time; 
QLQ C30 v3 = 30 item Core Quality of Life Questionnaire, version 3; QLQ-LC13 = 13-item Lung Cancer Quality of Life Questionnaire; RECIST 1.1 = Response Evaluation 
Criteria in Solid Tumors, version 1.1; SAE = Serious adverse event; SpO2 = Saturation of peripheral oxygen; T3 = Triiodothyronine; T4 = Thyroxine; TSH = Thyroid-stimulating 
hormone; W = Week.
a
For participants starting the maintenance phase with durvalumab monotherapy, who subsequently receive AZD2811 in a later cycle (ie, beyond Cycle 5), additional safety 
assessments and PK sampling are required. See Section 8.2. 
b
Only if short-acting G-CSF (filgrastim) is administered.
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All assessments, including 
 and safety labs, must be performed pre-dose, unless otherwise specified. 
Table 4
Schedule of Activities for the End of Treatment Period for Participants Entering the Maintenance Phase and 
Re-Treatment After Relapse Participants
Procedure
Disease 
Progression
EOT
FU
(90 days 
+/- 1 week 
after last 
dose)
Every 2 
months+/- 1 
week following 
FU
Notes
Details in 
CSP 
Section or 
Appendix
Vital signs
X
Section 
8.2.2
Physical examination
X
X
Skin to be assessed at each visit regardless of changes
Section 
8.2.1
ECOG performance status
X
Section 
8.2.6
Concomitant medications
X
X
X
Participant to return 
 
at Disease Progression/EOT
Section 6.5
AE/SAE assessment
X
X
X
Participants should be asked about any skin changes or 
rashes at each visit.
Section 8.3
Single 12-lead ECG
X
Section 
8.2.3
Hematology
X
Section 
8.2.4
Clinical chemistry
X
Section 
8.2.4
PT/PTT/INR
X
Section 
8.2.4
Fibrinogen and CRP
X
Section 
8.2.4
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Table 4
Schedule of Activities for the End of Treatment Period for Participants Entering the Maintenance Phase and 
Re-Treatment After Relapse Participants
Procedure
Disease 
Progression
EOT
FU
(90 days 
+/- 1 week 
after last 
dose)
Every 2 
months+/- 1 
week following 
FU
Notes
Details in 
CSP 
Section or 
Appendix
Pregnancy test 
X
X
In women of childbearing potential only.
Pregnancy testing will be performed monthly (28 days +/-
7 days) through 90 days post last dose or until a new 
treatment is initiated, whichever is shorter.
The pregnancy testing can be performed at a standard of 
care visit, and does not require a separate study visit.
Section 
8.2.4
Section 
8.6.2.2
Section 
8.6.2.3
Section 
8.6.2.4
Section 
8.6.2.5
Section 
8.6.2.6
Section 
8.6.2.7  
Section 
8.6.2.8
Section 
8.6.2.9
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Table 4
Schedule of Activities for the End of Treatment Period for Participants Entering the Maintenance Phase and 
Re-Treatment After Relapse Participants
Procedure
Disease 
Progression
EOT
FU
(90 days 
+/- 1 week 
after last 
dose)
Every 2 
months+/- 1 
week following 
FU
Notes
Details in 
CSP 
Section or 
Appendix
Section 
8.6.2.10
Section 
8.6.2.11
CT Scan or MRI 
Chest/Abdomen
RECIST v1.1 tumor assessments should be performed at W18, 
24, 30 and 36 ± 1 week and every 8 weeks ± 1 week thereafter.  
The weeks are referenced to the first dose of study intervention 
in the induction phase (Cycle 1 Day 1).
For participants who have discontinued treatment due 
to safety reasons only.
Section 
8.1.1
Survival Status/subsequent 
cancer therapy
X
A separate study visit is not required. Data from a 
standard of care visit or a phone call may be used.
Section 
8.1.2
Second progression assessment
X
Participants who discontinue study intervention following 
progression will be assessed every 8-12 weeks for a 
second progression (using the participant’s status at 
first/confirmed progression as the reference for 
assessment of second progression). A participant’s 
progression status is defined according to local standard 
clinical practice and may involve any of the following: 
objective radiological imaging, symptomatic progression, 
or death (using the participant’s status at first progression 
as the reference for assessment of second progression).
Section 
8.1.1
AE = Adverse event; 
; CRF = case report form;  CRP = C-reactive protein; CSP = Clinical study protocol; CT = Computed tomography; 
 DCO = data cut-off; 
; ECG = Electrocardiogram; ECOG = Eastern Cooperative 
Oncology Group; eCRF = electronic CRF; EOT – End of treatment; FU = Follow-up; INR = International normalized ratio; IV = Intravenous; MRI = Magnetic resonance imaging; 
OS = overall survival; PBMCs = peripheral blood mononuclear cells; PD = Progressive disease; PT = prothrombin time; PTT partial prothrombin time; RECIST 1.1 = Response 
Evaluation Criteria in Solid Tumors, version 1.1; SAE = Serious adverse event; SCLC = small-cell lung cancer; W = Week.
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Table 5
Schedule of Activities for Re-treatment after Relapse
Procedure
Screening
Re-
treatment 
Cycle 1
(cycle = 
 
)
Re-treatment 
Cycle 2
Re-
treatment 
Cycle 3 
Continued
Notes
Details in 
CSP 
Section or 
Appendix
Day -21 to -
1
Day (± 2 D)
Day (± 2 D)
Day 
(± 2 D)
Window (days) unless a 
dose delay is needed for 
toxicity management
NA
± 2
± 2
Informed consent
X
Eligibility criteria
X
Physical examination
X
X
X
X
Procedures can be performed as clinically 
indicated/less frequently if considered appropriate 
by the investigator or if not required by Institutional 
Guidelines with a minimum at the beginning of 
each cycle and at the end of treatment.
Section 
8.2.1
Vital signs
X
X
X
X
X
X
X
Procedures can be performed as clinically 
indicated/less frequently if considered appropriate 
by the investigator or if not required by Institutional 
Guidelines with a minimum at the beginning of 
each cycle and at the end of treatment.
Section 
8.2.2
ECOG performance 
status
X
X
X
X
Section 
8.2.6
Concomitant 
medications
X
X
X
X
X
X
X
X
X
At each visit
Section 6.5
AE/SAE assessment 
X
X
X
X
X
X
X
X
X
At each visit
Participants should be asked about any skin changes 
or rashes at each visit. AEs and SAEs will be 
collected until 90 days following the last dose of 
study intervention.
Section 8.3
and 8.2.7
C
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Table 5
Schedule of Activities for Re-treatment after Relapse
Procedure
Screening
Re-
treatment 
Cycle 1
(cycle = 
 
)
Re-treatment 
Cycle 2
Re-
treatment 
Cycle 3 
Continued
Notes
Details in 
CSP 
Section or 
Appendix
Day -21 to -
1
Day (± 2 D)
Day (± 2 D)
Day 
(± 2 D)
Window (days) unless a 
dose delay is needed for 
toxicity management
NA
± 2
± 2
Triplicate 12-lead ECGs
X
X
As clinically indicated
Section 
8.2.3
Hematology
X
X
X
X
X
X
X
Procedures can be performed as clinically 
indicated/less frequently if considered appropriate 
by the investigator or if not required by Institutional 
Guidelines with a minimum at the beginning of 
each cycle and at the end of treatment.
Section 
8.2.4
Clinical chemistry
X
X
X
X
X
X
X
Procedures can be performed as clinically indicated/less 
frequently if considered appropriate by the investigator or 
if not required by Institutional Guidelines with a minimum 
at the beginning of each cycle and at the end of treatment.
Section 
8.2.4
PT/PTT/INR
X
X
As clinically indicated
Section 
8.2.4
Fibrinogen and CRP
X
X
X
X
Pre-infusion of AZD2811 in each cycle
Section 
8.2.4
TSH, free T3, and free T4
X
X
X
X
Section 
8.2.4
Pregnancy test 
X
X
X
X
In women of childbearing potential only, at the 
beginning of each treatment cycle. Urine is 
acceptable.
Section 
8.2.4
C
C
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Table 5
Schedule of Activities for Re-treatment after Relapse
Procedure
Screening
Re-
treatment 
Cycle 1
(cycle = 
 
)
Re-treatment 
Cycle 2
Re-
treatment 
Cycle 3 
Continued
Notes
Details in 
CSP 
Section or 
Appendix
Day -21 to -
1
Day (± 2 D)
Day (± 2 D)
Day 
(± 2 D)
Window (days) unless a 
dose delay is needed for 
toxicity management
NA
± 2
± 2
CT Scan or MRI 
Chest/Abdomen
X
RECIST v1.1 tumor assessments should be 
performed at RC1, and every 8 weeks ± 1 
week thereafter until death, progressive 
disease, or the end of study)
Per 
Institutional 
Guidelines
Section 
8.1.1
CT Scan or MRI Pelvis 
/Additional Anatomy
As clinically indicated
Section 
8.1.1
Durvalumab 
administration
Section 4.1
and 6.2.2
AZD2811 administration
Section 4.1
and 6.2.1
G-CSF
Section 4.1
and 6.2.4
AE = Adverse event; CBCs = complete blood counts; CRP = C-reactive protein; CSP = Clinical study protocol; CT = Computed tomography; D = Day; ECG = Electrocardiogram; 
ECOG = Eastern Cooperative Oncology Group; G-CSF = granulocyte colony stimulating factor; INR = international normalized ratio; IP = Investigational product; 
IV = Intravenous; MRI = Magnetic resonance imaging; NA = not applicable;  PT = prothrombin time; PTT = partial prothrombin time; 
; RC1 = re-treatment 
cycle 1; RECIST 1.1 = Response Evaluation Criteria in Solid Tumors, version 1.1; SAE = Serious adverse event; T3 = Triiodothyronine; T4 = Thyroxine; 
TSH = Thyroid-stimulating hormone.
a
Only if short-acting G-CSF (filgrastim) is administered.
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2
INTRODUCTION
2.1
Study Rationale
Despite significant progress in the treatment of extensive stage small-cell lung cancer (ES-
SCLC) resulting from the addition of programmed cell death-ligand 1 (PD-L1) 
immunotherapy to platinum-etoposide, there remains an urgent need for more effective 
therapies that delay disease progression by prolonging the progression-free survival (PFS) and 
overall survival (OS) in this disease. Preliminary clinical data suggest that AZD2811 may be 
effective in stabilizing disease in later line SCLC participants. This trial will investigate 
whether a similar benefit can be demonstrated in first line (1L) ES-SCLC participants by 
adding AZD2811 to durvalumab maintenance therapy, following 
 of durvalumab plus 
platinum-etoposide induction therapy. Currently, no benefit is expected from adding 
AZD2811 to the induction therapy.
2.2
Background
Lung cancer is the second most common cancer and the leading cause of cancer death for men 
and women. It is estimated that 135,720 (72,500 men and 63,220 women) deaths from this 
disease will occur in 2020 in the United States (Cancer.Net, 2020 
https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/statistics).
Small-cell lung cancer accounts for 10 to 15 percent of all lung cancers. Small-cell lung 
cancer is perhaps the most aggressive form of the disease, distinguishable from non-SCLC by 
its rapid doubling time, high growth fraction, and early dissemination. It is strongly associated 
with tobacco smoking and is also associated with an extremely high mutation rate.
Regardless of stage, the current prognosis for patients with SCLC is unsatisfactory despite 
improvements in diagnosis and therapy made during the past 25 years. Without treatment, 
SCLC has the most aggressive clinical course of any type of pulmonary tumor, with median 
survival from diagnosis of only 2 to 4 months if untreated. About 10% of the total population 
of SCLC patients remains free of disease during the 2 years from the start of therapy, which is 
the time period during which most relapses occur. Even these patients, however, are at risk of 
dying from lung cancer (both small and non-small cell types) (Fry et al, 1996; Johnson et al, 
1990; Lassen et al, 1995; Murray et al, 1993). Limited disease was defined as tumor tissue that 
could be encompassed in a single radiation port, and ES disease was defined as any tumor that 
extended beyond the boundaries of a single radiation port. At present, limited disease is 
identified in ~30% of patients, and ES is identified in ~70% of patients. 
Four to six cycles of platinum-based chemotherapy, etoposide in combination with either 
cisplatin or carboplatin, without maintenance therapy has been the standard care for patients 
with ES-SCLC for the past 25 years (Pignon et al, 1992), and are recommended by major 
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worldwide oncology treatment guidelines, ie, ASCO, NCCN, ESMO. Despite high initial 
response rates of up to 70% (Rossi et al, 2012), it is estimated that 80% of patients with 
limited stage and almost all patients with ES-SCLC will relapse or experience disease 
progression (Clark and Ihde, 1998). Therefore, the prognosis for patients with SCLC in 
general and particularly for ES-SCLC remains poor; the reported 2-year survival for 
ES-SCLC is only 5% and 5 years survival rate is less than 2% (Rossi et al, 2012). 
2.2.1
AZD2811
The mammalian Aurora kinases (A, B, and C) are a family of highly conserved 
serine/threonine kinases that perform key roles in the regulation of separate points of the cell 
cycle. The Aurora kinases, and Aurora kinase B in particular, represent potential targets for 
anticancer therapy.
AZD2811, formerly designated AZD1152 hydroxyl-quinazoline pyrazole anilide, is a potent 
and selective inhibitor of Aurora B kinase activity and has been incorporated into a 
nanoparticle (NP) carrier for intravenous (IV) administration (Song et al, 2016). The 
phosphate pro-drug of AZD2811, known as AZD1152 (barasertib), reached Phase II of 
clinical development as a continuous IV infusion. The pro-drug was converted rapidly in 
plasma to the active drug, AZD2811. While promising efficacy was seen with barasertib in the 
acute myeloid leukemia (AML) population, continuous prolonged IV infusion was required. 
In addition, barasertib was limited in the solid tumor populations by a high frequency of bone 
marrow toxicities and little to no clinical response.
AZD2811 has been incorporated into a NP carrier that has been shown to provide prolonged 
exposure to AZD2811. 
Nonclinical studies have shown increased efficacy and decreased toxicity for AZD2811, 
formulated as a NP, when compared to barasertib treatment in in vivo SCLC and diffuse large 
B-cell lymphoma models (Ashton et al, 2015; Ashton et al, 2016).
A detailed description of the chemistry, pharmacology, efficacy, and safety of AZD2811 is 
provided in the Investigator’s Brochure (IB).
2.2.2
Durvalumab
Durvalumab is a human monoclonal antibody (mAb) of the immunoglobulin G (IgG) 1 kappa 
subclass that blocks the interaction of PD-L1 (but not programmed cell death-ligand 2 [PD-
L2]) with programmed cell death-protein 1 (PD-1) on T cells and cluster of differentiation 
(Larkin et al)80 (B7.1) on immune cells. It is being developed by AstraZeneca for use in the 
treatment of cancer. Durvalumab has been engineered to reduce antibody-dependent cellular 
cytotoxicity and complement-dependent cytotoxicity. In vitro studies demonstrate that 

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durvalumab antagonizes the inhibitory effect of PD-L1 on primary human T cells, resulting in 
their restored proliferation and release of interferon gamma (IFNγ) (Stewart et al, 2015).
To date, durvalumab has been given to more than 6000 patients as part of ongoing studies 
either as monotherapy or in combination with other anticancer agents. Details on the safety 
profile of durvalumab therapy are summarized in Section 8.3.12. Refer to the current 
durvalumab IB for a complete summary of nonclinical and clinical information, including 
safety, efficacy, and pharmacokinetics (PK).
In March 2020, the United States Food and Drug Administration (FDA) approved the use of 
durvalumab in combination with etoposide and either carboplatin or cisplatin as first-line 
treatment of patients with ES-SCLC. Efficacy of this combination in patients with previously 
untreated ES-SCLC was investigated in CASPIAN (NCT03043872), a randomized, 
multicenter, active-controlled, open-label trial. The CASPIAN trial assessed the benefit of 
combining durvalumab (± tremelimumab) with etoposide plus either cisplatin or carboplatin 
(platinum-etoposide standard of care [SOC]) in treatment-naïve patients with ES-SCLC (Paz-
Ares et al, 2019). Participants were enrolled between 27 March 2017 and 29 May 2018, for a 
total of 268 participants allocated to the durvalumab-SOC group and 269 to the SOC group. 
Durvalumab-SOC was associated with a significant improvement in OS, (hazard ratio: 0.73 
[95% confidence interval (CI) 0.59 to 0.91; p = 0.0047]). The median OS was 13.0 months 
(95% CI 11.5 to 14.8) in the durvalumab-SOC group versus 10.3 months (9.3 to 11.2) in the 
SOC group. Thirty-four percent (26.9% to 41.0%) versus 25% (18.4% to 31.6%) of patients 
were alive at 18 months. The study treatment was well tolerated overall, with any-cause 
adverse events (AEs) (Grade 3 or 4) in 163 (62%) of 265 treated patients in the durvalumab 
plus SOC group and 166 (62%) of 266 in the SOC group. Adverse events leading to death 
occurred in 13 (5%) and 15 (6%) patients. Overall, the first-line durvalumab plus SOC 
significantly improved OS in patients with ES-SCLC versus a clinically relevant control 
group. Safety findings were consistent with the known safety profiles of all drugs received.  
2.2.3
Rationale for Combination of AZD2811 and durvalumab in 1L ES-
SCLC
Recent development in segmentation of small cell lung cancer (SCLC) disease into subtypes 
(Rudin et al, 2019) has, for the first time, enabled rational combination proposals for agents 
that preferentially target different subtypes (Gay et al, 2021).These subtypes include SCLC-
ASCL1 (SCLC-A), -NEUROD1 (SCLC-N) and -POU2F3 (SCLC-P) defined by their 
eponymous driver transcription factor programs, and a fourth subtype alternatively called 
SCLC-YAP1 or ‘inflamed’ (SCLC-I), defined by pathobiological features, such as high 
expression of mesenchymal and inflammatory genes (Rudin et al, 2019; Gay et al, 2021). 
Analysis of subtype outcome under standard of care treatment including the anti-PDL1 
antibody atezolizumab in the Impower133 phase 3 study has shown that the median OS and 

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the magnitude of benefit with the addition of atezolizumab is numerically greater in SCLC-I 
compared to the other subtypes. A median OS in SCLC-I of more than 18 months was seen in 
the Etoposide-Platinum (EP) + atezolizumab arm, compared with just over 10 months in the 
EP + placebo arm. By contrast, the addition of atezolizumab produced little benefit in SCLC-
A and SCLC-N (Gay et al, 2021). However, recently published data from relapsed patients 
and models demonstrates the inherent plasticity within this tumor type and that subclonal 
subtype variants can repopulate tumors that previously responded to subtype-selective therapy 
(Stewart et al, 2020). This plasticity and concomitant heterogeneity which can drive rapid 
adaptation and relapse therefore requires therapeutic strategies that embody principles of 
parallel mechanistic targeting, rather than synergy within a specific mechanism, so that the 
final regimen addresses the therapeutic needs of most patients, and prevents emergent 
resistance through subtype switching. 
 
 
 
 
 
 
 
 
 
 
 
 
 
. However, the hypothesis that inhibition of Aurora 
kinase B can drive generation of micronuclei in tumor cells (Harding et al, 2017), 
 
 
 
 
 
 
 
 
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2.3
Benefit/Risk Assessment
2.3.1
Risk Assessment
Table 6
Risk Assessment
Identified and potential risk of
clinical significance
Summary of data/rationale for risk
Mitigation strategy
Study interventions
AZD2811
Identified risks associated with 
AZD2811 include: 
•
neutropenia, 
•
febrile neutropenia, 
•
rash,
•
sepsis.
The following are considered potential 
risks for AZD2811:
•
lymphocytopenia and 
leukocytopenia, 
•
anemia, 
•
thrombocytopenia, 
•
stomatitis/oral mucositis, 
•
diarrhoea, 
•
nausea and vomiting,
•
alopecia/hair loss.
Potential risks for AZD2811 have been 
determined from nonclinical studies 
with AZD2811, previous clinical 
experience with AZD1152 (barasertib), 
and clinical experience with other drugs 
targeting inhibition of Aurora kinases.
Toxicity management 
of AZD2811 is 
presented in 
Section 8.5.1.
A dermatology 
consultation is 
recommended for 
participants who 
present with rash. 
G-CSF is mandatory 
for every cycle in 
which participants 
receive AZD2811.
Durvalumab
Identified risks associated with 
durvalumab include:
•
pneumonitis, 
•
interstitial lung disease, 
•
hepatitis, 
•
diarrhea/colitis,
•
hypothyroidism, 
•
hyperthyroidism, 
•
blood TSH increased, 
•
blood TSH decreased, 
•
adrenal insufficiency,
•
type 1 diabetes mellitus, 
•
hypophysitis/hypopituitarism and 
diabetes insipidus, 
•
nephritis, 
•
rash/dermatitis, 
•
myocarditis, 
This section includes identified risks 
and potential risks for durvalumab of an 
inflammatory and/or immune-mediated 
nature, related to the mechanism of 
action of durvalumab and related to 
mAb therapeutics in general.
The risks presented can 
be mitigated through
close monitoring, early 
detection, and prompt 
treatment with 
corticosteroids, 
immunosuppressants, 
and/or endocrine 
therapy. Investigators 
should adhere to the 
Toxicity Management 
Guidelines 
(Section 8.5.2) by 
performing a thorough 
evaluation to rule out 
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Table 6
Risk Assessment
Identified and potential risk of
clinical significance
Summary of data/rationale for risk
Mitigation strategy
•
myositis/polymyositis, 
•
infusion-related reactions,
•
pancreatitis,
•
encephalitis.
Potential risks for durvalumab include:
•
other rare or less frequent events 
with a potential immune-mediated 
etiology, e.g., pericarditis, 
sarcoidosis, uveitis, and other 
events involving the eye (e.g., 
keratitis and optic neuritis), skin 
(e.g., scleroderma, vitiligo, and 
pemphigoid), and hematological 
(e.g., hemolytic anemia and 
immune thrombocytopenic 
purpura), rheumatological events 
(polymyalgia rheumatic and 
autoimmune arthritis), 
neuropathy/neuromuscular 
toxicities (e.g., myasthenia gravis, 
Guillain-Barre syndrome), 
vasculitis, and non-infectious 
meningitis.
•
hypersensitivity reactions, 
including:
#
anaphylaxis and allergic 
reaction
#
cytokine release syndrome
#
immune complex disease
•
infections (excluding urinary tract 
infection, bronchitis, sepsis, 
bacterial sepsis, and urosepsis)
Standard of Care
NA
Cisplatin: Cumulative renal toxicity 
associated with Cisplatin injection is 
severe. Other major dose-related 
toxicities are myelosuppression, nausea, 
and vomiting and other toxicities 
(vascular, serum electrolyte disturbance, 
hyperuricemia, neurotoxicity, ocular, 
and hepatotoxicity). Anaphylactic-like 
reactions to cisplatin injection have been 
reported. 
Toxicity management 
of cisplatin, 
carboplatin, and 
etoposide will be 
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Table 6
Risk Assessment
Identified and potential risk of
clinical significance
Summary of data/rationale for risk
Mitigation strategy
Carboplatin: Bone marrow suppression 
is dose related and may be severe, 
resulting in infection and/or bleeding. 
Anemia may be cumulative and may 
require transfusion support. 
Nausea/vomiting is frequently observed 
as well as urea elevations and electrolyte 
disturbance.
Anaphylactic-like reactions to 
carboplatin have been reported and may 
occur within minutes of carboplatin 
administration.
Etoposide: Dose-limiting bone marrow 
suppression is the most significant 
toxicity associated with etoposide 
therapy. Other possible adverse events 
are the occurrence of an anaphylactic 
reaction (chills, fever, tachycardia, 
bronchospasm, dyspnea, and 
hypotension), nausea/vomiting, 
asthenia/malaise, alopecia, chills, and/or 
fever.
Study procedures
Routine blood draws and disease 
assessments have a well-established risk 
profile, which is addressed by the 
institutional standards. Biopsy-taking is 
not devoid of risk but is considered 
unavoidable for determining the type of 
the disease to be treated.
Biopsy procedures are 
set up in such a way 
that the risk for 
bleeding and other 
risks are reduced at 
maximum.
The most serious adverse reactions that 
may occur during G-CSF treatment 
include anaphylactic reaction, serious 
pulmonary adverse events (including 
interstitial pneumonia and ARDS), 
capillary leak syndrome, and severe 
splenomegaly/splenic rupture. 
G-CSF: The most commonly reported 
adverse reactions are pyrexia, 
musculoskeletal pain (which includes 
bone pain, back pain, arthralgia, 
myalgia, pain in extremity, chest pain, 
and neck pain), anemia, vomiting, and 
nausea. In clinical trials in cancer 
patients, musculoskeletal pain was mild 
or moderate in 10% of patients and 
severe in 3% of patients.
Toxicity management 
of G-CSF will be 
according to the local 
label.
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Table 6
Risk Assessment
Identified and potential risk of
clinical significance
Summary of data/rationale for risk
Mitigation strategy
No drugs comparable to AZD2811 are 
known. 
NA
AE = adverse event; ARDS = acute respiratory distress syndrome; AST = aspartate aminotransferase; 
G-CSF = granulocyte colony stimulating factor; GGT = gamma-glutamyltransferase; IV = intravenous; 
mAb = monoclonal antibody; NA = not applicable; TSH = thyroid-stimulating hormone.
2.3.2 Benefit Assessment
AZD2811 has demonstrated preliminary activity in relapsing SCLC in an expansion cohort of 
the AZD2811 first in human trial (NCT02579226). Twenty-one patients who had failed SOC 
and up to 3 lines of therapy were treated with 
 AZD2811 every 
 
Clinical benefit (defined as complete response [CR], partial response [PR], or stable disease 
[SD] > 8 weeks) was demonstrated in > 50% of the participants, and median OS in this patient 
population was 9.95 months (data on record).
The monotherapy safety profile of durvalumab and AZD2811 suggest that both drugs can be 
combined in the absence of overlapping toxicities. Both drugs have demonstrated clinical 
benefit in SCLC and there is clear medical need to improve the efficacy of the current therapy 
in ES-SCLC. Therefore, investigating the efficacy of the combination of durvalumab with 
AZD2811 is a rational next step.
2.3.3 Overall Benefit: Risk Conclusion
The risks related to the current chemotherapy SOC (platinum-etoposide) for ES-SCLC are 
well known and widely documented to be myelosuppression and nausea/vomiting. The 
benefits are well recognized, resulting in this treatment being universally used to treat 1L 
SCLC patients for many years. The risks are well understood, and an extensive concomitant 
therapy guideline and practice has been put in place that follows Institutional Guidelines 
considered most appropriate to work in the lowest risk setting as much as feasible. Extensive 
stage-SCLC, with the exception of adding PD-L1 immunotherapy such as durvalumab to the 
current Platinum-Etoposide standard, has had no real therapeutic improvement for many 
years. A wide range of new and less new therapies have been explored, but all with dismal 
effect (Amarasena et al, 2015; Fiegl et al, 2014; Kalemkerian and Schneider, 2017).
AZD2811 has demonstrated preliminary clinical benefit, stabilizing disease, in an extension 
Phase I cohort of patients with relapsing SCLC that had been treated with between 1 to 3 prior 
lines of therapy. It is therefore anticipated that AZD2811 is highly likely to have a similar 
disease-stabilizing effect when used in the earlier 1L maintenance setting. The potential risks 
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associated with patients being exposed to AZD2811 are considered to be outweighed by the 
benefit, as observed in the late line setting.
The benefit of durvalumab in combination with platinum-etoposide for the treatment of 
ES-SCLC was demonstrated in the CASPIAN trial, which resulted in regulatory approval in 
Singapore in February 2020 and by the FDA in March 2020. Durvalumab has also been 
recommended for approval in the European Union (EU) by the Committee for Medicinal 
Products for Human Use for ES-SCLC.
More detailed information about the known and expected benefits and potential risks of 
AZD2811 and durvalumab may be found in the IBs for AZD2811 and durvalumab.
Taking into account the extensive monitoring and safety measures proposed in this study to 
minimize risk to participants, and the potential risks identified for durvalumab and AZD2811 
as maintenance therapy, the anticipated benefits that may be afforded to participants with ES-
SCLC are justified.

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3
OBJECTIVES AND ENDPOINTS
Table 7
Objectives and Endpoints
Objectives
Endpoints
Primary
To evaluate the efficacy of AZD2811 + durvalumab 
by assessment of the proportion of participants alive 
and progression free at 12 months APF12 who have 
not progressed during EP-durvalumab based 
induction therapy.
The proportion of participants alive and progression free at 
12 months APF12 will be defined as the Kaplan-Meier 
estimate of PFS per RECIST v1.1 as assessed by the 
investigator at local site at 12 months, in participants who 
enter the maintenance phase. 
Secondary
To evaluate efficacy of AZD2811 + durvalumab by 
assessment of the proportion of participants alive at 
12 months OS12, 15 months OS15, and 18 months 
OS18 who have not progressed during EP-
durvalumab based induction therapy.
The proportion of participants alive at 12 months OS12, 15 
months OS15, and 18 months OS18 will be defined as the 
Kaplan-Meier estimate of OS at 12 months, 15 months, 
and 18 months, respectively, in participants who enter the 
maintenance phase.
To evaluate efficacy of AZD2811 + durvalumab by 
assessment of the proportion of participants alive and 
progression free at 6 months APF6 and 9 months 
APF9 who have not progressed during EP-
durvalumab based induction therapy.
The proportion of participants alive and progression free at 
6 months APF6 and 9 months APF9 will be defined as the 
Kaplan-Meier estimate of PFS per RECIST v1.1 as 
assessed by the investigator at local site at 6 months and 9 
months, respectively, in participants who enter the 
maintenance phase.
To evaluate efficacy of EP-durvalumab by 
assessment of Objective response rate (ORR in the 
induction phase. 
ORR is defined as the proportion of participants with 
measurable disease at baseline who have a confirmed CR 
or PR, by the investigator at local site per RECIST v1.1 in 
the induction phase (all participants).
To evaluate efficacy of AZD2811 + durvalumab by 
assessment of ORR in the participants who had not 
progressed during EP-durvalumab based induction 
therapy. 
ORR is defined as the proportion of participants with 
measurable disease at baseline who have a confirmed CR 
or PR, by the investigator at local site per RECIST v1.1, in 
participants who enter the maintenance phase.
To evaluate efficacy of AZD2811 + durvalumab by 
assessment of PFS in participants who had not 
progressed during EP-durvalumab based induction 
therapy. 
PFS is defined as time from date of first dose study 
intervention in the induction phase until progression per 
RECIST v1.1 or death due to any cause. The median 
Kaplan-Meier estimate in participants who enter the 
maintenance phase.
To evaluate efficacy of AZD2811 + durvalumab by 
assessment of OS in participants who had not 
progressed during EP-durvalumab based induction 
therapy. 
OS is defined as time from date of first dose study 
intervention in the induction phase until the date of death 
due to any cause. The median Kaplan-Meier estimate in 
participants who enter the maintenance phase.
To assess the safety and tolerability profile of study 
intervention in SCLC.
Safety and tolerability will be evaluated in terms of AEs, 
vital signs, physical examination, clinical chemistry, TSH, 
PT/PTT/INR, hematology, ECG, and urinalysis, as well as 

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Table 7
Objectives and Endpoints
Objectives
Endpoints
treatment delays, dose reductions, and dose 
discontinuations.
To evaluate the PK of durvalumab and AZD2811.
Concentration of durvalumab, and AZD2811 and its 
metabolite in serum and whole blood, respectively. 
To evaluate the effect of AZD2811 + durvalumab on 
SCLC symptoms and health-related QoL using 
EORTC QLQ-C30 and QLQ-LC13.
EORTC QLQ-C30: Symptoms (fatigue, pain, 
nausea/vomiting, dyspnea, loss of appetite, insomnia, 
constipation, and diarrhea). Health-related 
QoL/functioning (physical function, role function, 
emotional function, cognitive function, social function, 
and global health status/QoL).
EORTC QLQ-LC13: Disease-related symptoms (dyspnea, 
cough, hemoptysis, chest pain, arm/shoulder pain, and 
other pain).
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Table 7
Objectives and Endpoints
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Table 7
Objectives and Endpoints
AE = adverse event; APF6 = proportion of participants alive and progression free at 6 months from first dose of 
study therapy in the induction phase (ie, PFS rate at 6 months); APF9 = proportion of participants alive at 9 
months from the first dose of study therapy in the induction phase (ie, PFS rate at 9 months); APF12 = proportion 
of participants alive and progression free at 12 months from first dose of study therapy in the induction phase (ie, 
PFS rate at 12 months); CR = complete response; 
 
; DoR = duration of response; ECG = electrocardiogram; EORTC = European Organization for Research 
and Treatment of Cancer; EP = etoposide and platinum-based chemotherapy; 
INR = international normalized ratio; KM = Kaplan-Meier; ORR = objective response rate; OS = overall 
survival; OS12 = proportion of participants alive at 12 months (ie, OS rate at 12 months); OS15 = proportion of 
participants alive at 15 months (ie, OS rate at 15 months); OS18 = proportion of participants alive at 18 months 
(ie, OS rate at 18 months); PD = progressive disease; 
 PFS = 
progression-free survival; PFS2 = progression-free survival after subsequent anticancer therapy; PK = 
pharmacokinetics; PR = partial response; PT = prothrombin time; PTT = partial prothrombin time; RECIST = 
Response Evaluation Criteria in Solid Tumors; 
; QLQ-C30 = 30-item Core Quality of 
Life Questionnaire; QLQ-LC13 = 13-item Lung Cancer Quality of Life Questionnaire; QoL = quality of life; 
SCLC = small-cell lung cancer; 
; TSH = thyroid-
stimulating hormone.
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4
STUDY DESIGN
4.1
Overall Design
On 14 December 2021 AstraZeneca took the decision to terminate enrolment for this study 
prior to completion due to the evolving benefit risk profile of AZD2811 that does not support 
further development for the first-line treatment of patients with extensive stage small-cell lung 
cancer. Patients already enrolled in the study were able to continue. However, no further 
patients were permitted to start AZD2811 treatment and ongoing patients transitioning into the 
maintenance phase after this date were offered durvalumab monotherapy. As a result of the 
early termination, the data cut-off for the final analysis in this study is planned for 18 June 
2022. 
Sections from CSP v8.0 are retained throughout this protocol for reference. Clinical Study 
Protocol v8.0 was prepared to include urgent safety measures via a Dear Investigator Letter; 
however, CSP V 8.0 was not implemented due to early termination. Clinical Study Protocol 
v8.0 is superseded by CSP v9.0.
This is a Phase II, open-label, multicenter, single arm, global study to determine the efficacy, 
safety, and tolerability of AZD2811 + durvalumab maintenance therapy in patients with 
ES-SCLC who do not progress during etoposide and platinum-based chemotherapy (EP) 
combined with durvalumab induction therapy as first-line treatment. A schematic diagram of 
the study is presented in Figure 1. 
This study plans to assign treatment to approximately 100 eligible participants at sites 
worldwide and treatment will be conducted in 2 phases – an initial induction phase followed 
by a maintenance phase. 
Tumor assessments are scheduled at screening as baseline with follow-up assessments every 
6 weeks (Q6W; ± 1 week) up to Week 36 following the date of first administration of 
induction therapy and every 8 weeks (Q8W) ± 1 week thereafter until confirmed objective 
disease progression, unless the investigator, in agreement with the Sponsor, agrees otherwise. 
For patients eligible to receive AZD2811 treatment, every effort should be made to schedule 
the scan within 1 week prior to dosing with AZD2811; scan results MUST be reviewed prior 
to dosing to confirm the absence of disease progression.  
Global recruitment will be complete when approximately 100 participants have been assigned 
in the induction phase and a minimum of 80 evaluable participants have entered the 
maintenance phase. It is anticipated that assigning treatment to approximately 100 eligible 
participants into the induction phase will achieve the minimum of 80 evaluable participants 
required for the maintenance phase. In the event that 100 participants does not yield the 
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be enrolled and assigned into the study. In the event that a biomarker is identified that is 
associated with improved efficacy, additional participants may be recruited. Study participants 
who fail screening can be rescreened a single time.
4.1.1
Induction Phase
Participants who fulfil all the inclusion criteria and none of the exclusion criteria will be 
treated for 
 on a 
 schedule in the induction phase with platinum-based induction 
therapy (cisplatin or carboplatin plus etoposide) + durvalumab according to Table 8 and 
Section 6.1. 
Table 8
Study Intervention During the Induction Phase
Order of 
Administration
Agent and Dose
Route
Duration
Observation Time
Schedule
1 
Durvalumab 
(
IV
2
Carboplatin 
(AUC 5-6) 
IV
OR
Cisplatin 
(75-80 mg/m2)
IV
3
Etoposide 
(80-100 mg/m2) 
IV
Note: Participants whose weight falls to 30 kg or below (≤30 kg) should receive weight-based dosing equivalent 
to 20 mg/kg of durvalumab 
until the weight improves to > 30 kg, at which point the participant should start 
receiving the fixed dosing of durvalumab 
. The doses of cisplatin and carboplatin should be calculated 
on 
 of each treatment cycle.
AUC = area under the curve; 
 EP = etoposide and platinum-based chemotherapy; IV = Intravenous; 
PIG = per Institutional Guidelines; 
.
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At the end of this induction phase, participants will be assessed for disease progression, per 
Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Participants who AstraZeneca 
and the investigator determine may not continue treatment after progressive disease during the 
induction phase will be followed up for AE/serious adverse event (SAE) reporting for 90 days 
following the final dose of study intervention.
Following confirmed disease progression, further therapy will be offered by the investigator.
4.1.2
Maintenance Phase
4.1.2.1
Maintenance Phase Overview
Participants who have not progressed per RECIST v1.1 at the end of the induction phase and 
who meet maintenance phase eligibility criteria will continue into the maintenance phase of 
the trial and be treated with AZD2811 + durvalumab as maintenance therapy (Table 9) until 
radiological progressive disease (PD), unless there is unacceptable toxicity, withdrawal of 
consent, or another discontinuation criterion is met (Section 7.1).
Table 9
Study Intervention During the Maintenance Phase
Day and order of 
administration in 
each cycle
Agent and dose
Route
Duration
Observation time
Schedule
AZD2811 
 a
IV
Durvalumab 
 
IV
Filgrastim 0.5 MU 
(5 μg)/kg/day SC from 
(DAILY until at 
least 
 of each 
cycle AND the ANC 
has recovered to 
≥1.5 × 109/L)
or
Neulasta (pegfilgrastim) 
6 mg dose SC on 
only
SC
a
Dose reduction levels are provided in Section 6.6.1
b
Participants are treated until PD unless there is unacceptable toxicity, withdrawal of consent, or another 
discontinuation criterion is met
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ANC = absolute neutrophil count; G-CSF = granulocyte colony stimulating factor; IV = intravenous; MU = million units; 
N/A = not applicable; PD = progressive disease; 
; SC = subcutaneously.
Hematopoietic growth factors (short-acting granulocyte colony stimulating factor [G-CSF] 
[filgrastim] or long-acting G-CSF [pegfilgrastim]), must be administered as primary 
prophylaxis on/from 
 of every maintenance cycle to limit the duration of neutropenia, 
and to minimize the risk of neutropenic fever and infections. If short-acting G-CSF 
(filgrastim) is used, administer DAILY until at least 
 of each cycle AND the ANC has 
recovered to ≥ 1.5 × 109/L. Long-acting G-CSF should be administered once only per cycle on 
 
For all participants who are treated through progression with durvalumab monotherapy, the 
investigator should ensure participants do not have any significant, unacceptable, or 
irreversible toxicities that indicate continuing treatment would not further benefit the 
participant. AZD2811 must not be administered through progression.
4.1.2.2
Safety Run-In
 
 
 
 
 
Nevertheless, because the amount of safety data on this combination is still expected to be 
from a limited number (≤6) of participants when this trial starts, a safety run-in will be 
conducted, in which six participants will be followed for (at least) 1 cycle to assess safety of 
the AZD2811 + durvalumab combination. The study procedures and safety assessments 
undertaken for the safety run-in period will be as per the Schedule of Activities (Table 1). The 
safety run-in will comprise participants as defined in the inclusion and exclusion criteria 
(Section 5.1 and 5.2) to provide the earliest opportunity to assess tolerability of the 
combination in those six participants.
After administration of the first dose of AZD2811 + durvalumab to the first participant, at 
least 24 hours must be allowed before administration to the second participant in case of 
unexpected acute toxicity.
A participant will be evaluable for the safety run-in (described as dose-limiting toxicity 
[DLT]) safety assessment if they have received at least 75% of the scheduled AZD2811 and 
durvalumab doses, or had a DLT. Non-evaluable participants will be replaced. After the 
completion of ≥
 (≥1 cycle) dosing in the first 6 evaluable maintenance therapy 
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participants, all available safety data (including, but not limited to, DLTs, adverse events of 
special interest (AESIs), laboratory safety assessments, and clinical examinations) will be 
assessed to judge if the combination is safe and tolerable. This assessment, and subsequent 
decision to continue dosing further participants, will be undertaken by the SRC. The SRC 
membership is described in Appendix A 5. The role and responsibilities of SRC members, as 
well as the purpose and timing of the SRC meetings, are described in the SRC Charter.
The purpose of the safety run-in is to confirm the dose of AZD2811 and durvalumab in the 
combination setting. Treatment of new participants entering the maintenance phase with 
AZD2811 + durvalumab will be paused (after ~six participants) while the SRC convenes to 
assess the safety data at the end of the safety run-in phase if a DLT event is observed in any of 
the first ~six participants. In absence of clarity on the feasibility of the proposed combination 
maintenance therapy, transition of participants beyond the approximately six participants to 
the maintenance therapy, can be paused until confirmation of feasibility. In the event of a 
pause, new participants entering the maintenance phase would receive treatment with 
durvalumab monotherapy, as this represents standard of care treatment for ES-SCLC patients. 
Following a pause, if dosing with AZD2811 resumes, participants receiving durvalumab 
monotherapy will be allowed to start dosing with AZD2811 if maintenance phase eligibility 
criteria are met. In the absence of a DLT event in any of the first ~six participants, treatment 
with AZD2811 + durvalumab into the maintenance phase will not be paused while the SRC 
convenes. Participants from the safety run-in phase will contribute to the required treatment 
assignment as described in Section 9.3. 
4.1.2.2.1
Results of the Safety Run-In
Treatment in the maintenance phase of the trial began in June 2021 and the SRC completed an 
initial assessment of the safety run-in cohort in September 2021. While no DLTs were 
experienced by the first six participants, one participant experienced an SAE of neutropenic 
sepsis with a fatal outcome and one participant experienced an SAE of febrile neutropenia 
with a fatal outcome during the second cycle of AZD2811 treatment (ie,
 Both SAEs 
were attributed to AZD2811 treatment by the investigators. Additional information about 
these events and the identified risk of sepsis has been added to the Investigator’s Brochure.
Treatment with AZD2811, of new participants entering the maintenance phase, was put on 
hold while additional data analyses were conducted, and the following protocol amendments 
were proposed to ensure the safety of current and future participants:
!
Maximum AZD2811 dose permitted will be 
; maintenance phase eligibility 
criteria must be confirmed prior to dosing the first cycle of AZD2811
!
AZD2811 must not be administered if there is any suspicion of disease progression. 
Every effort should be made to schedule tumour evaluation scans within 1 week prior 
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to dosing with AZD2811; scan results MUST be reviewed prior to dosing to confirm 
the absence of disease progression.  
!
AZD2811 must not be administered if there is any suspicion of infection; consider 
(prophylactic) antibiotics for participants experiencing Grade 4 ANC or at a high risk 
of infection. If infection is suspected, work up should be performed to identify whether 
there is an infection.
!
AZD2811 dose will be reduced if a patient experiences Grade 4 ANC, irrespective of 
time to recovery
!
An additional safety visit on Day 12 of 
) 
has been introduced to identify low ANC earlier in the cycle (from Phase I experience, 
the nadir is expected between 10 to 15 days after AZD2811 dosing).
After implementation of the above recommendations in CSP v8.0, an additional safety run-in 
cohort will be assessed by the SRC according to Section 4.1.2.2.
4.1.3
DLT Criteria
A DLT will be considered for any toxicity observed unless unequivocally due to underlying 
malignancy or an extraneous cause.  
The DLT evaluation period is defined as the first 
 from the start of AZD2811 + 
durvalumab administration. Toxicity will be graded according to the National Cancer Institute 
Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0. The definition of an 
evaluable participant is found in Section 4.1.4. The following toxicities constitute a DLT:  
!
Grade 4 neutropenia, or febrile neutropenia.
!
Grade 4 anemia.
!
Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia associated with bleeding.
!
Concurrent Grade ≥3 total bilirubin (TBL), hepatic transaminase (alanine 
aminotransferase [ALT] or aspartate aminotransferase [AST]) and alkaline phosphatase 
lasting > 48 hours, or any change in liver function test results consistent with Hy’s Law 
(HL; see Appendix E).
!
Any ≥ Grade 3 non-hematologic AE with the exception of:
∀
Grade 3 nausea, vomiting, stomatitis, and/or diarrhea that is controlled within 4 days 
with standard supportive care. Use of prophylactic mouthwash to prevent stomatitis 
is allowed and should be used according to local site practices.
∀
Grade 3 fatigue and/or decreased appetite (anorexia) that resolves within 5 days
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∀
Grade 3 elevations in ALT/AST that return to initial eligibility criteria within 7 days 
of study drug interruption.
!
Inability to receive ≥75% of all doses in Cycle 1 of maintenance due to treatment--related 
toxicity.
!
Non-hematologic toxicity of ≥ Grade 3 (at any time during treatment) that, in the 
judgment of the investigators and the Study Physician, is dose limiting.
4.1.4
Definition of DLT-Evaluable Participants
An evaluable participant for the purpose of the safety run-in decision is defined as a 
participant who has received AZD2811 + durvalumab and either:
!
Has completed the minimum safety evaluation requirements of the study (ie, safety 
assessments in the SoA [Table 1] up to and including 
 in Cycle 1 maintenance of 
AZD2811 + durvalumab) and received at least 75% of the scheduled AZD2811 and 
durvalumab doses, or 
!
Has experienced a DLT in Cycle 1 of maintenance therapy
4.1.5
Study Conduct Mitigation During Study Disruptions Due to Cases of 
Civil Crisis, Natural Disaster, or Public Health Crisis
The guidance given below supersedes instructions provided elsewhere in this CSP and should 
be implemented only during cases of civil crisis, natural disaster, or public health crisis (e.g., 
during quarantines and resulting site closures, regional travel restrictions, and considerations if 
site personnel or study participants become infected with SARS-CoV-2 or similar pandemic 
infection), which would prevent the conduct of study -related activities at study sites, thereby 
compromising the study site staff or the participant’s ability to conduct the study. The 
investigator or designee should contact the study Sponsor to discuss whether the mitigation 
plans below should be implemented.  
To ensure continuity of the clinical study during a civil crisis, natural disaster, or public health 
crisis, changes may be implemented to ensure the safety of study participants, maintain 
compliance with Good Clinical Practice (GCP), and minimize risks to study integrity. 
Where allowable by local health authorities, ethics committees, healthcare provider guidelines 
(e.g., hospital policies) or local government, these changes may include the following options: 
!
Rescreening: Additional rescreening for screen failure and to confirm eligibility to 
participate in the clinical study can be performed in previously screened participants. The 
investigator should confirm this with the designated Study Physician. 
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!
Home or Remote visit: Performed by a site qualified Health Care Professional (HCP) or 
HCP provided by a third-party vendor.
!
Telemedicine visit: Remote contact with the participants using telecommunications 
technology, including phone calls, virtual or video visits, and mobile health devices. 
For further details on study conduct during civil crisis, natural disaster, or public health crisis, 
refer to Appendix H. 
4.2
Scientific Rationale for Study Design
4.2.1
Rationale for 
 of Induction Therapy 
The use of platinum-based chemotherapy in combination with etoposide has been SOC for 
SCLC for over 40 years. Current investigations are now adding immunotherapeutics to 
chemotherapeutics to broaden antitumor responses. In March 2020, the FDA approved the use 
of durvalumab in combination with 4 cycles of etoposide and either carboplatin or cisplatin, 
and durvalumab in maintenance therapy, as first-line treatment of patients with ES-SCLC. 
Efficacy of this combination in patients with previously untreated ES-SCLC was investigated 
in CASPIAN, a randomized, multicenter, active-controlled, open-label trial. The evaluation 
was based on the comparison of patients randomized to durvalumab plus chemotherapy, 
followed by durvalumab maintenance therapy, versus chemotherapy alone. Median OS was 
13.0 months in the durvalumab plus chemotherapy arm and shown to be superior compared to 
10.3 months in the chemotherapy alone arm having 6 cycles of chemotherapy (Paz-Ares et al, 
2019). As such, 4 cycles of chemotherapy, when combined with durvalumab and followed by 
durvalumab maintenance therapy, appears to be superior to 6 cycles of chemotherapy alone.
The durvalumab + platinum-based induction chemotherapy induction regimen will be 
administered for 
 followed, in participants who do not have PD at the end of 
induction, by AZD2811 + durvalumab combination maintenance therapy 
 until disease 
progression or unacceptable toxicity.
4.2.2
Rationale for AZD2811 and Durvalumab Maintenance Therapy 
The interest of durvalumab in 1L ES-SCLC has been established with giving durvalumab in 
combination with platinum-etoposide and in maintenance therapy in terms of landmark 12-
month PFS and OS, as demonstrated in the CASPIAN study. AZD2811 has demonstrated 
activity in relapsing SCLC in an expansion cohort of the AZD2811 first in human trial 
(NCT02579226). Twenty-one patients who had failed SOC and up to 3 lines of therapy were 
treated with 
 AZD2811 
 Clinical benefit (defined as CR, PR, or SD > 8 weeks) 
was demonstrated in > 50% of the participants, and median OS in this patient population was 
9.95 months (data on record).
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Nonclinical and clinical studies have indicated that blockade of immune checkpoints 
(PD-1/PD-L1) can have a positive effect on disease control in SCLC patients, as described in 
Section 2.2.2.
The therapy safety profile of durvalumab and AZD2811 suggest that both drugs can be 
combined in the absence of overlapping toxicities. Both drugs have demonstrated clinical 
benefit in SCLC, and there is clear medical need to improve the efficacy of the current therapy 
in ES-SCLC. Therefore, investigating the efficacy of the combination of durvalumab with 
AZD2811 is a rational next step. 
4.3
Justification for Dose
4.3.1
Rationale for Dose of Platinum-based Chemotherapy
The doses of platinum-based chemotherapy to be used in this study are the approved doses for 
this indication. 
4.3.2
Rationale for Dose of AZD2811
The initial proposed AZD2811 dosing schedule, 
 on 
 with mandatory 
G-CSF on 
 is based on data from a Phase I dose escalation and expansion study: 
D6130C00001/NCT02579226. 
In Part A of study D6130C00001, several AZD2811 dosing schedules were evaluated. Doses 
ranging from 
 AZD2811 were administered IV on 
 of every 
cycle. After switching to single day treatment per cycle, the cycle length was shortened 
to cycles of 
 duration to decrease time between infusions and increase the dose 
intensity, evaluating doses ranging from 
to
mg infused on Day 1. On 
 G-CSF 
was introduced and mandated to ensure recovery of neutrophils before Day 1 of the next 
cycle. AZD2811 
 on 
 with mandatory G-CSF on 
 was declared the 
maximum tolerated dose (MTD) and recommended Phase II dose. Activity and safety of this 
regimen was further supported by data from a dose expansion phase: D6130C00001 Part B.
Exposure-response analysis of data from D6130C00001 indicates that an AZD2811 dose 
above 
 would result in unfavorable rates of severe (Grade 4) neutropenia, further 
supporting the proposed AZD2811 dosing schedule. Therefore, G-CSF is mandated for this 
dose and schedule. Further details of the results from Study D6130C00001 are available in the 
AZD2811 IB.
Subsequent to the review of the safety run-in cohort of the current study (see 
Section 4.1.2.2.1), the starting dose of AZD2811, in combination with durvalumab in the 
maintenance phase, has been reduced to a maximum of 
 on 
 with 
mandatory G-CSF on/from 
to decrease the rate of Grade 4 neutropenia. 
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Dose reductions for AZD2811 are detailed in Section 6.6.1.
4.3.3
Rationale for Dose of Durvalumab
The dosing schedule proposed during the induction phase is aligned with the standard fixed 
dosing of 
 durvalumab for 
 of 
 duration followed by durvalumab 
maintenance therapy, which is supported by efficacy and safety as well as tolerability data 
from the CASPIAN clinical trial. 
The durvalumab dosing regimen during the maintenance phase was aligned to the AZD2811 
 regimen with standard fixed dosing of 
 durvalumab 
 The proposed 
durvalumab regimen is dose-matched (ie, equivalent dose per week) to the regimen tested in 
the CASPIAN clinical trial maintenance setting – durvalumab 
 every 
 dosing 
– and further supported by preliminary safety as well as tolerability data from the HUDSON 
(NCT03334617) clinical trial. 
4.4
End of Study Definition
The end of the study is defined as the date of the last scheduled procedure shown in the SoA 
for the last treated participant in the study, globally.
The study may be terminated at individual centers if the study procedures are not being 
performed according to GCP or if the site is unable to recruit sufficient numbers of 
participants into the study.
The AstraZeneca Study Team may also terminate the study prematurely if concerns for safety 
arise within this study or in any other study with any agent used in this study.
As a result of the early termination of this study, the data cut-off (DCO) for the final analysis is 
planned for 18 June 2022, approximately 5 months after last participant first dose.Main data 
collection will stop at that point.Data analysis will be performed and a clinical report will be 
written based on this dataset. Serious AEs will be collected per Section 8.3.2.
Participants who are receiving treatment at the time of DCO can either choose to discontinue 
from the study or, when the investigator believes participants are gaining clinical benefit, may 
continue to receive study treatment, following discussion with, and approval from, the 
AstraZeneca Study Team.
Patients’ treatment may be continued:
-
Within the current study, or
-
Within a rollover or safety extension study, if available, or
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-
Within a drug supply program (commercial supply or other compassionate use 
program),  if applicable
In case of treatment continuation within the current study:
-
Assessments will revert to standard of care at each site
-
There will be no further data collection, except SAE reporting. The Clinical Study 
Database will be closed
-
Paper form process will be used for SAE reporting. All SAEs, overdoses and 
pregnancies would be reported until 30 days after last dose
-
Investigational product will be supplied to sites manually outside of the IXRS system. 
Drug dispensation and reconciliation will be handled by site at each patient’s visit
-
Study will remain open until last patient completes treatment. Last Subject Last Visit 
will be defined as the last patient’s treatment discontinuation
In case a rollover or safety extension study is available for patients remaining in this 
study after analysis is finalized, they may be transferred to one of these studies:
-
A rollover or safety extension study would have to be fully approved by Regulatory 
and Ethics bodies applicable for the patient’s site
-
The new study would ensure proper treatment continuation with visit assessments per 
its own protocol
-
Visit assessments would cover the minimum needed for safety oversight. May also 
cover assessments required for long term use analysis
-
Any patient that was to move to such a study would need to be reconsented beforehand
If study drug is approved in a given market for use in the disease under study, patients may be 
discontinued and switched to marketed product. Drug supply options will vary depending on 
the specific country and would be proposed to patients if they are considered the best way to 
continue treatment by both AZ and the investigator.
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5
STUDY POPULATION
Extensive stage-SCLC treatment naïve patients who have not progressed per RECIST v1.1 
after induction with EP-durvalumab comprise the study population. Prospective approval of 
protocol deviations to recruitment and enrollment criteria, also known as protocol waivers or 
exemptions, are not permitted.
5.1
Induction Phase Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age
1
Participant must be ≥18 years of age, at the time of signing the informed consent.
Type of Participant and Disease Characteristics
2
Histologically or cytologically documented extensive stage (American Joint Committee 
on Cancer Stage [7th edition] IV SCLC [T any, N any, M1 a/b]), or T3 or T4 tumor stage 
due to multiple lung nodules that are too extensive or have tumor/nodal volume that is too 
large to be encompassed in a tolerable radiation plan.
∀
Brain metastases; must be asymptomatic or treated and stable off steroids and anti-
convulsants for at least one month prior to study treatment. Participants with 
suspected brain metastases at screening should have a computed tomography 
(CT)/magnetic resonance imaging (MRI) of the brain prior to study entry.
3
Provision of an archived tumor tissue block  or unstained slides if block cannot be 
provisioned) where such samples exist. If not, a mandatory fresh biopsy will be required 
at screening (refer to Section 8.6.2.1 and Laboratory Manual for details).
4
Participants must be considered suitable to receive a platinum-based chemotherapy 
regimen, combined with durvalumab, as first-line treatment for the ES-SCLC. 
Chemotherapy must contain either cisplatin or carboplatin in combination with etoposide. 
5
Life expectancy ≥12 weeks.
6
World Health Organization (WHO) Eastern Cooperative Oncology Group (ECOG) 
Performance Status of 0 or 1 at treatment assignment.
7
Body weight > 30 kg.
8
At least one lesion, not previously irradiated, that can be accurately measured at baseline 
as ≥10 mm in the longest diameter (except lymph nodes, which must have a short axis 
≥15 mm) with CT or MRI and that is suitable for accurate repeated measurements as per 
RECIST v1.1 guidelines.
9
No prior exposure to immune-mediated therapy including, but not limited to anti-PD-1, 
anti-PD-L1, and anti-PD-L2 antibodies, excluding therapeutic anticancer vaccines.
10 Adequate organ and marrow function as defined below:

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∀
Hemoglobin ≥9.0 g/dL (without blood transfusion in the last 2 weeks).
∀
Absolute neutrophil count ≥1.5 × 109/L (use of granulocyte colony stimulating factor 
is not permitted at screening).
∀
Platelet count ≥100 × 109/L (without platelet transfusion in the last 2 weeks).
∀
Serum bilirubin ≤1.5 × the upper limit of normal (ULN). This will not apply to 
participants with known Gilbert’s syndrome, who will be allowed to participate in the 
study, in consultation with their physicians.
∀
In participants without hepatic metastasis: ALT and AST ≤2.5 × ULN.
∀
In participants with hepatic metastases, ALT and AST ≤5 × ULN.
∀
Measured or calculated creatinine clearance (CL): > 60 mL/min for participants on 
cisplatin and > 50 mL/min for participants on carboplatin, as determined by 
Cockcroft-Gault (using actual body weight):
∀
Males:
Creatinine CL = 
Weight (kg) × (140 – Age)
(mL/min)
72 × Serum creatinine (mg/dL)
∀
Females:
Creatinine CL = 
Weight (kg) × (140 – Age) × 0.85
(mL/min)
72 × Serum creatinine (mg/dL)
Informed Consent
11 Capable of giving signed informed consent as described in Appendix A, which includes 
compliance with the requirements and restrictions listed in the informed consent form 
(ICF) and in this protocol.
12 Provision of signed and dated written Optional Genetic Research Information informed 
consent prior to collection of samples for optional genetic research that supports Genomic 
Initiative.
5.2
Induction Phase Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1
Medical contraindication to etoposide-platinum (carboplatin or cisplatin) based 
chemotherapy and/or durvalumab, including a history of immune mediated reactions, e.g. 
pneumonitis.
2
Any history of radiotherapy to the chest prior to systemic therapy or planned 
consolidation chest radiation therapy. Radiation therapy outside of the chest for palliative 
care or prophylaxis (e.g. bone metastasis or prophylactic cranial irradiation (PCI) for 

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brain metastases) is allowed, but must be completed before first dose of the study 
medication.
3
i) Any concurrent chemotherapy, investigational product (IP), biologic, or hormonal 
therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer related 
conditions (e.g., hormone replacement therapy) is acceptable.
ii) For the first six patients that are in the safety run-in group only: Concomitant use of the 
clinical BCRP inhibitors curcumin, cyclosporine A or eltrombopag. Culinary use of 
spices containing curcumin, such as curry and turmeric, is acceptable. 
4
Major surgical procedure (as defined by the investigator) within 28 days prior to the first 
dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
5
History of allogeneic organ transplantation.
6
Has a paraneoplastic syndrome (PNS) of autoimmune nature, requiring systemic 
treatment (systemic steroids or immunosuppressive agents) or has a clinical 
symptomatology suggesting worsening of PNS. 
7
Active or prior documented autoimmune or inflammatory disorders (including 
inflammatory bowel disease [e.g., colitis or Crohn’s disease], diverticulitis with the 
exception of diverticulosis, systemic lupus erythematosus, sarcoidosis syndrome, or 
Wegener syndrome [granulomatosis with polyangiitis, Graves’ disease, rheumatoid 
arthritis, hypophysitis, and uveitis, etc.]). The following are exceptions to this criterion:
∀
Participants with vitiligo or alopecia
∀
Participants with hypothyroidism (e.g., following Hashimoto syndrome) and stable 
on hormone replacement 
∀
Any chronic skin condition that does not require systemic therapy
∀
Participants without active disease in the last 5 years may be included but only after 
consultation with the Study Physician
∀
Participants with celiac disease controlled by diet alone
8
Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, 
interstitial lung disease (ILD) such as pneumonitis, symptomatic congestive heart failure, 
uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, serious chronic 
gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations 
that would limit compliance with study requirement, substantially increase risk of 
incurring AEs, or compromise the ability of the participant to give written informed 
consent.
9
History of another primary malignancy except for: 
∀
Malignancy treated with curative intent and with no known active disease ≥5 years 
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∀
Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of 
disease
∀
Adequately treated carcinoma in situ without evidence of malignant disease 
10 History of leptomeningeal carcinomatosis.
11 History of active primary immunodeficiency.
12 Active infection, including tuberculosis (clinical evaluation that includes clinical history, 
physical examination, and radiographic findings, and tuberculosis testing in line with 
local practice), hepatitis B virus (HBV; known positive HBV surface antigen [HbsAg] 
result), hepatitis C, or human immunodeficiency virus (HIV; positive HIV 1/2 
antibodies). Participants with a past or resolved HBV infection, or vaccination (defined as 
the presence of hepatitis B core antibody and absence of HbsAg), are eligible. Participants 
positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain 
reaction is negative for HCV ribonucleic acid (Nguyen et al). Participants suspected for 
COVID-19 infection will need to have a negative screen test before treatment assignment. 
If a COVID-19 test is performed, the results should be reported in the EDC. 
Prior/Concomitant Therapy
13 Current or prior use of immunosuppressive medication within 14 days before the first 
dose of durvalumab. The following are exceptions to this criterion:
∀
Intranasal, inhaled, topical steroids or local steroid injections (e.g., intra-articular 
injection).
∀
Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone 
or its equivalent.
∀
Steroids as premedication for hypersensitivity reactions (e.g., CT scan 
premedication). Premedication with steroids for chemotherapy is acceptable.
14 Receipt of live, attenuated vaccine within 90 days prior to the first dose of study 
intervention. Note: Participants, if assigned, should not receive live vaccine while 
receiving study intervention and up to 90 days after the last dose of study intervention.
15 Known allergy or hypersensitivity to AZD2811, durvalumab, etoposide, carboplatin, 
cisplatin, or any of their excipients (e.g., polyethylene glycol [PEG]).
16 Participant has had prescription or non-prescription drugs, or other products known to be
strong inhibitors/inducers of CYP3A4 that cannot be discontinued prior to Day 1 of the 
maintenance phase (refer to Section 6.5.1 for list of drugs and specific washout periods) 
and withheld throughout the maintenance phase until 2 weeks after the last dose of study 
drug.
17 Prior randomization or treatment in a previous AZD2811 or durvalumab clinical study 
regardless of treatment arm assignment.

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Prior/Concurrent Clinical Study Experience
18 Previous treatment assignment in the present study, except for participants meeting 
criteria for re-treatment after relapse.
19 Concurrent participation in another clinical study, unless it is an observational 
(noninterventional) clinical study or during the follow-up period of an interventional 
study.
20 Participation in another clinical study with a study intervention during the last 4 weeks 
prior to Cycle 1 Day 1.  
Other Exclusions
21 Involvement in the planning and/or conduct of the study (applies to both AstraZeneca 
staff and/or staff at the study site).
22 Judgment by the investigator that the participant should not participate in the study if the 
participant is unlikely to comply with study procedures, restrictions, and requirements.
23 Female participants who are pregnant or breastfeeding, or male or female participants of 
reproductive potential who are not willing to employ effective birth control from 
screening to 7 months after the last dose durvalumab + EP or AZD2811 + durvalumab 
(Section 5.3).
5.3
Maintenance Phase Eligbility Criteria
In order to continue study treatment in the maintenance phase of the study (ie,
 and 
beyond), participants must meet the following criteria prior to initiating dosing with 
AZD2811.
5.3.1
Maintenance Phase Inclusion Criteria
1
Body weight > 30 kg.
2
Adequate organ and marrow function as defined below:
∀
Absolute neutrophil count ≥1.5 × 109/L.
∀
Platelet count ≥75 × 109/L.
∀
Serum bilirubin ≤1.5 × ULN.
∀
In participants without hepatic metastasis: ALT and AST ≤2.5 × ULN.
∀
In participants with hepatic metastases: ALT and AST ≤5 × ULN.
∀
Measured or calculated creatinine CL: > 50 mL/min, as determined by 
Cockcroft-Gault (using actual body weight) (see Section 5.1).
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5.3.2
Maintenance Phase Exclusion Criteria 
1
Progressive disease as per RECIST v1.1 guidelines. A scan must have been performed 
within 1 week prior to first dose of AZD2811.
5.4
Lifestyle Considerations
The following restrictions apply while the participant is receiving study treatment and for the 
specified times before and after:
!
Female participants of childbearing potential who are sexually active with a non-sterilized 
male partner must use at least 2 highly effective methods of contraception (see Table 10) 
from the time of screening and must agree to continue using such precautions for 7 
months after the last dose of AZD2811 and/or durvalumab, whichever is the longer time 
period. Male partners of a female participant must use male condom plus spermicide 
throughout this period. Cessation of birth control after this point should be discussed with 
a responsible physician. Female participants should refrain from breastfeeding throughout 
this period. In addition, female participants must refrain from egg donation while on study 
and for 7 months after the final dose of AZD2811 and/or durvalumab, whichever is the 
longer time period.
!
Non-sterilized male participants who are sexually active with a female partner of 
childbearing potential must use male condom plus spermicide from screening through 
9 months after the last dose of study drug. Male participants should refrain from sperm 
donation for 9 months after the last dose of AZD2811 and/or durvalumab, whichever is 
the longer time period. Female partners of a male participant must use a highly effective 
method of contraception throughout this period.
Females of childbearing potential are defined as those who are not surgically sterile (ie, 
bilateral tubal ligation, salpingectomy, bilateral oophorectomy, or complete hysterectomy) or 
post-menopausal (defined as 12 months with no menses without an alternative medical cause).
Acceptable non-hormonal birth control methods include:
!
Total/True abstinence: When the participant refrains from any form of sexual intercourse 
and this is in line with their usual and/or preferred lifestyle; this must continue for the 
total duration of the study and for at least 7 months after the last dose of study drug. Note: 
Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods, or 
declaration of abstinence solely for the duration of a study) and withdrawal are not 
acceptable methods of contraception.
!
Vasectomized sexual partner PLUS male condom. With participant assurance that partner 
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!
Tubal occlusion PLUS male condom.
!
Intrauterine device PLUS male condom. Coils must be copper-banded.
Highly effective methods of contraception are described in Table 10. A highly effective 
method of contraception is defined as one that results in a low failure rate (ie, less than 1% per
year) when used consistently and correctly. Note that some contraception methods are not 
considered highly effective (e.g., male or female condom with or without spermicide; female 
cap, diaphragm, or sponge with or without spermicide; non-copper containing intrauterine 
device; progestogen only oral hormonal contraceptive pills where inhibition of ovulation is 
not the primary mode of action [excluding Cerazette/desogestrel, which is considered highly 
effective]; and triphasic combined oral contraceptive pills).
Table 10
Highly effective methods of contraception (< 1% failure rate)
Barrier/intrauterine methods
Hormonal methods
•
Copper T intrauterine device
•
Levonorgestrel-releasing intrauterine system 
(e.g., Mirena®)a
•
Implants: Etonogestrel-releasing implants (e.g., 
Implanon® or Norplant®)
•
Intravaginal Devices: 
Ethinylestradiol/etonogestrel-releasing 
intravaginal devices (e.g., NuvaRing®)
•
Injection: Medroxyprogesterone injection (e.g., 
Depo-Provera®)
•
Combined Pill: Normal and low dose combined 
oral contraceptive pill
•
Patch: Norelgestromin/ethinylestradiol-releasing 
transdermal system (e.g., Ortho Evra®)
•
Minipill: Progesterone based oral contraceptive 
pill using desogestrel: Cerazette® is currently 
the only highly effective progesterone based pill
a
This is also considered a hormonal method.
5.5
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 demography, screen failure details, 
eligibility criteria, and any SAE.
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened. Only one rescreening is allowed in the study. Participants must complete the 

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rescreening within 4 weeks of the initial screenfail date (maximum of 7 weeks between initial 
consent and Cycle 1 Day 1 or second screen failure). Rescreened participants should be 
assigned the same participant number as for the initial screening.
Individuals who start induction therapy and are later found not to be eligible, should be 
discussed with the Study Physician before the next treatment.
6
STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), or 
placebo intended to be administered to or medical device(s) utilized by a study participant 
according to the study protocol. Study interventions are described in Table 11 and details of 
dosing levels and order of dosing for the induction and maintenance phases are provided in 
Table 8 and Table 9, respectively. For dose modifications of AZD2811, please see 
Section 6.6.1. For information on rescue medication(s), please refer to Section 6.5.4
Table 11
Study Interventions
Phase of treatment
Study intervention
Duration of study intervention
Induction Phase
Durvalumab + Carboplatin or 
Cisplatin + Etoposide 
, unless objective disease progression is 
observed during induction phase
Maintenance Phase
AZD2811 + Durvalumab + 
G-CSF
Until objective disease progression a
a
Participants are treated until progressive disease in the maintenance phase unless there is unacceptable 
toxicity, withdrawal of consent, or another discontinuation criterion is met.
G-CSF = granulocyte colony stimulating factor.
Participants must receive platinum-based chemotherapy and durvalumab for the first 
. 
Participants without evidence of PD (per RECIST v1.1) who meet maintenance phase 
eligibility criteria will receive AZD2811 and durvalumab and G-CSF during the maintenance 
phase.
6.1
Study Intervention(s) Administered
6.1.1
Investigational Products
AstraZeneca will supply AZD2811 and durvalumab. Refer to Table 12 for information on 
investigational study interventions.
Dose reductions for toxicity are only permitted for AZD2811; the dose of durvalumab can be 
delayed for toxicities, but dose reductions are not allowed (see Section 6.6). Participants must 
be eligible to receive both durvalumab and AZD2811 to enter the maintenance phase. 
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Table 12
List of Investigational Study Interventions
Intervention name
AZD2811
Durvalumab
Dose form
Dosage level(s)
Induction phase: N/A
Maintenance phase: 
 
Induction phase: 
Maintenance phase: 
 
Route of administration
IV infusion
IV infusion
Handling instructions
Refer to Handling Instructions 
manual
Refer to Handling Instructions manual
Dosing instructions
See Table 9 and Section 6.2.1 plus 
Section 6.6.1 for dose reductions
See Table 8 (Induction Phase), 
Table 9 (Maintenance Phase) and 
Section 6.2.2
Packaging and labeling
Study intervention will be provided in 
 vials. Each 
 vial will 
be labeled as required per country 
requirement
Study intervention will be provided in 
 vials. Each 
 vial will 
be labeled as required per country 
requirement
Provider
AstraZeneca
AstraZeneca
IV = intravenous; N/A = not applicable; 
.
6.1.2
Non-investigational Products
The chemotherapy agents (etoposide, cisplatin, and carboplatin) and G-CSF will either be 
locally sourced or, under certain circumstances when local sourcing is not feasible, 
AstraZeneca will centrally supply the drug, which will be labeled in the local language in 
accordance with regulatory guidelines (Table 13). In the EU, etoposide, cisplatin, carboplatin, 
and G-CSF are considered auxiliary medicinal products according to EU clinical trials 
guidance (EU, 2017).
Chemotherapy is considered a “non-investigational drug” as it is a recommended SOC in 
international guidelines. Chemotherapy will be administered in accordance with the 
recommendation in international guidelines (NCCN, 2020).
Platinum-based chemotherapy should continue for 
. Chemotherapy dosing will be as 
described in Table 13.
Each chemotherapy agent will be administered in accordance with local guidelines and 
premedication will be provided.
If any chemotherapy agent is permanently discontinued early (prior to completing 
) as 
a result of a toxicity, e.g. hypersensitivity reaction, may enter the maintenance phase after 
consultation with the Study Physician, and as long as the participant meets the maintenance 
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phase eligibility criteria. However, if any chemotherapy agent is permanently discontinued 
early (prior to completing 
) as a result of disease progression during induction, the 
participant will not enter the maintenance phase.
Hematopoietic growth factors (short-acting G-CSF [filgrastim] or long-acting G-CSF 
[pegfilgrastim], see Section 6.2.4), must be administered as primary prophylaxis on/from 
 
 of every maintenance phase cycle to limit the duration of neutropenia, and to minimize the 
risk of neutropenic fever and infections caused by AZD2811 (Table 13). If short-acting 
G-CSF (filgrastim) is administered, DAILY dosing should continue until at least 
 AND 
the measured neutrophil nadir is passed (expected between Days 
 after AZD2811 
dosing) and the neutrophil count has recovered to ≥1.5 × 109/L. Long-acting G-CSF should 
be administered once only per cycle on 
Table 13
Non-Investigational Medicinal Products for this Study
Intervention 
name
Etoposide
Cisplatin
OR carboplatin
G-CSF
Dose form
Liquid for infusion
Liquid for infusion
Liquid for infusion
Dosage level(s)
Etoposide 80–100 mg/m² 
Investigator’s choice of 
carboplatin AUC 5–6 
mg/mL/min or cisplatin
75–80 mg/m² 
Filgrastim 0.5 MU 
(5 μg)/kg/day SC from 
(DAILY until at least 
 of each cycle AND 
the ANC has recovered to 
≥1.5 × 109/L)
or 
Neulasta (pegfilgrastim) 
6 mg dose SC on 
Route of 
administration
IV infusion
IV infusion
SC
Use
Background treatment
Background treatment
Supportive therapy
Sourcing
Provided locally by the 
study sitea
Provided locally by the study 
sitea
Provided locally by the 
study sitea
a
Under certain circumstances when local sourcing is not feasible, a SOC treatment may be supplied centrally 
through AstraZeneca.
ANC = absolute neutrophil count; AUC = area under the curve; G-CSF = granulocyte colony stimulating factor; 
IV = intravenous; MU = million units; PIG = per Institutional Guidelines; 
; SC = 
subcutaneous; SOC = standard of care.
6.1.3
Duration of Treatment and Criteria for Treatment After Initial 
Assessment of PD
Maintenance treatment will start on 
. Participants who do not have any evidence 
of radiological disease progression during the induction phase (
 of EP-durvalumab) 
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and who meet maintenance phase eligibility criteria (see Section 5.3) will continue into the 
maintenance phase of the trial. 
In the rare instances when the RECIST v1.1-defined radiological findings are considered 
equivocal by the investigator or there is doubt whether or not there is evidence of objective 
progression (e.g., technical issues, including image artifacts), the participant may not move 
into the maintenance phase of the study without prior discussion with the Sponsor.
Upon initial assessment of PD, treatment with AZD2811 must be discontinued. Treatment 
with durvalumab may be continued until radiological PD is confirmed by the subsequent scan, 
unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation 
criterion is met. Participants with rapid tumor progression or with symptomatic progression 
that requires urgent medical intervention (e.g., central nervous system [CNS] metastasis, 
respiratory failure due to tumor compression, or spinal cord compression) will not be eligible 
to continue study treatment. All efforts should be put in place to perform a disease assessment 
to document this disease progression.
Post final data cut-off
Participants who are receiving treatment at the time of DCO can either choose to discontinue 
from the study or, when the investigator believes participants are gaining clinical benefit, may 
continue to receive study treatment, following discussion with, and approval from, the 
AstraZeneca Study Team. For participants continuing to receive study treatment following the 
final DCO and database closure assessments will revert to standard of care.
6.2
Preparation/Handling/Storage/Accountability
1
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received, and any discrepancies are 
reported and resolved before use of the study intervention.
2
Only participants enrolled and assigned study treatment may receive study intervention 
and only authorized site staff may supply or administer study intervention. All study 
intervention must be stored in a secure, environmentally controlled, and monitored 
(manual or automated) area in accordance with the labeled storage conditions with access 
limited to the investigator and authorized site staff.
3
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records).
4
Further guidance and information for the final disposition of unused study interventions 
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6.2.1
AZD2811
AZD2811 is presented as a 
, 
contained in a 
 glass vial, containing approximately 
 of 
suspension at an AZD2811 concentration of 
. The cartons and vials will be 
individually labeled. 
AZD2811 IP vials must be stored 
; for specific storage conditions, please see the 
product label. 
Preparation of AZD2811 doses for administration
Refer to the AZD2811 Handling Instructions manual (provided separately to study centers) for 
information on the product vial thawing procedure and dose preparation. 
AZD2811 must not be infused through an administration set containing a 0.2-μm or 0.22-μm 
filter, whereas durvalumab must be infused through a 0.2-μm or 0.22-μm filter. Therefore, 
AZD2811 and durvalumab must be infused through different infusion lines.  
6.2.2
Durvalumab
Durvalumab will be supplied by AstraZeneca as a 
 vial concentrate for solution for 
infusion. It has a label-claim volume of 
 and a density of 
 
Investigational product vials are stored refrigerated in original packaging until use to prevent 
prolonged light exposure. For specific storage conditions, please see the product label.
Preparation of durvalumab doses for administration with an IV bag
Refer to the Durvalumab Handling Instructions manual (provided separately to study centers) 
for information on dose preparation. 
Durvalumab must be infused through a 0.2-μm or 0.22-μm filter, whereas AZD2811 must not
be infused through a 0.2-μm or 0.22-μm filter. Therefore, the products must be infused 
through different infusion lines.   
6.2.3
Standard of Care: EP
Etoposide and platinum-based chemotherapy will be locally sourced or centrally supplied by 
AstraZeneca and will be administered according to prescribing information or treatment 
guidance in general use by the Investigating site. Under certain circumstances when local 
sourcing is not feasible, AstraZeneca will centrally supply the drug, and it will be labeled with 
local language translated text in accordance with regulatory guidelines. 
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6.2.4
G-CSF
Granulocyte-CSF (filgrastim or pegfilgrastim including generic formulations of each) will be 
locally sourced and will be administered according to prescribing information or treatment 
guidance in general use by the Investigating site. 
Granulocyte-CSF (filgrastim or pegfilgrastim including generic formulations of each) must be 
administered on 
 as a primary prophylaxis. Granulocyte-CSF (filgrastim) daily dosing 
should continue until at least 
 and the measured neutrophil nadir is passed (expected 
between 
 after AZD2811 dosing) and the neutrophil count has recovered to 
≥1.5 × 109/L, and must be discontinued 48 hours prior to the next dose of AZD2811. Note: 
PEGylated G-CSF, e.g., pegfilgrastim, may not be given later than 
 (in a 
cycle) 
due to its long half-life. Complete blood counts should be collected and reviewed on Days 8, 
12 (Cycles 5 and 6) and/or 15 at a minimum, or more frequently as clinically indicated.
6.3
Measures to Minimize Bias: Randomization and Blinding
This is an open-label, non-randomized study. All participants will receive the study 
intervention. Participants will receive a participant number when the informed consent is 
signed. A cap of 25% of participants receiving cisplatin will be applied and managed through 
the interactive voice/web response system (IXRS). A cap of 10% of participants with brain or 
CNS metastases will be applied and managed using the IXRS. Data will be reviewed on a 
regular basis by the medical study team in order to ensure the safety of the participants.
6.4
Study Intervention Compliance
Participants will receive study intervention directly from the investigator or designee, under 
medical supervision. The date and start and stop times of treatments administered in the clinic 
will be recorded in the source documents and in the electronic Case Report Form (eCRF). The 
dose of study intervention 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 
intervention. 
6.5
Concomitant Therapy
All medications, including vaccines, over-the-counter medications, prescription medications, 
vitamins, and/or herbal supplements from the time of ICF until end of study treatment will be 
recorded in the source and eCRF. The name of the therapy, reason for use, start/stop dates of 
administration, dose, and frequency will be recorded, in addition to: 
!
Reason for use
!
Dates of administration, including start and end dates
!
Dosage information, including dose and frequency
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!
Was this “Break-through pain-therapy Yes/No”, where break-through pain-therapy is 
defined as therapy taken for pain at the choice of the participant in addition to the usual 
daily dose 
Participants will be asked to complete a simple diary to record breakthrough pain medication 
use, and the data will be entered into the EDC. 
Antibiotics taken within 90 days of Cycle 1 Day 1 will be recorded in the CRF. 
The Study Physician should be contacted if there are any questions regarding concomitant 
therapy.
Participants must be instructed not to take any medications, including over-the-counter 
products, without first consulting with the investigator.
6.5.1
Permitted Concomitant Medication
6.5.1.1
Permitted Concomitant Medication for AZD2811
Permitted concomitant medication for AZD2811 include the following:
!
No routine prophylactic antiemetics or premedication will be given during maintenance 
therapy. However, these medications may be administered for symptoms when they occur 
and may be given prophylactically afterwards.
!
Supportive care and other medications that are considered necessary for the participant’s 
wellbeing may be given at the discretion of the investigator and should be reported 
accordingly. AZD2811 must not be administered if there is any suspicion of infection; 
consider (prophylactic) antibiotics for participants experiencing Grade 4 ANC or at a high 
risk of infection. If infection is suspected, work up should be performed to identify 
whether there is an infection.
!
Participants already receiving erythropoietin at the time of screening may continue to 
receive it, provided they have been receiving it for more than one month at the time study 
intervention is started. Prophylactic erythropoietin should not be started during Cycle 1 of 
the study but may be started during Cycle 2 and thereafter.
!
Participants may receive treatment with megestrol acetate when prescribed for appetite 
stimulation.
!
Participants may take low dose warfarin or a coumarin preparation for port prophylaxis.
6.5.1.2
Permitted Concomitant Medication for Durvalumab
Permitted supportive concomitant medications for durvalumab are provided in Table 14. Refer 
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Table 14
Supportive medications for durvalumab
Supportive medication/class of drug:
Usage:
Concomitant medications or treatments (e.g., 
acetaminophen or diphenhydramine) deemed 
necessary to provide adequate prophylactic or 
supportive care, except for those medications 
identified as “prohibited,” as listed below in Section 
6.5.2.2
To be administered as prescribed by the investigator
Best supportive care (including antibiotics, 
nutritional support, correction of metabolic 
disorders, optimal symptom control, and pain 
management [including palliative radiotherapy to 
non-target lesions, etc])
Should be used, when necessary, for all participants
Inactivated viruses, such as those in the influenza 
vaccine
Permitted
6.5.2 Prohibited Concomitant Medication and Treatments
6.5.2.1
Prohibited Concomitant Medication for AZD2811
To ensure participant safety, the following potent inhibitors of CYP3A4 must not be used 
during the maintenance phase for any participant receiving AZD2811. While this is not an 
exhaustive list, it covers the known potent inhibitors, which have most often previously been 
reported to be associated with clinically significant drug interactions. A complete list, which is 
updated regularly, may be found here https://drug-
interactions.medicine.iu.edu/MainTable.aspx: 
!
ketoconazole, 
!
itraconazole, 
!
ritonavir, 
!
indinavir, 
!
saquinavir, 
!
telithromycin, 
!
clarithromycin, and 
!
nelfinavir.
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In addition, to avoid potential reductions in exposure due to drug interactions, the following 
CYP3A4 inducers should be avoided: 
!
phenytoin, 
!
rifampicin, 
!
rifapentine, 
!
rifabutin, 
!
carbamazepine, 
!
phenobarbitone, 
!
nevirapine, 
!
modafinil, and 
!
St John’s Wort (Hypericum perforatum).
For participants taking any of the above, the required washout periods prior to starting the 
maintenance phase are 5 weeks for phenobarbitone, and 3 weeks for any of the others.
Herbal supplements that strongly modulate CYP3A4 must not be used during the maintenance 
phase. The use of other (or combinations of) natural/herbal products that may modulate 
CYP3A4 should be discouraged. 
After entry into the maintenance phase, if the use of any potent inducers or inhibitors of 
CYP3A4 are considered necessary for the participant’s safety and welfare, the investigator 
must contact the Study Physician. A decision to allow the participant to continue in the study 
will be made on a case-by-case basis.  
During the maintenance phase, metformin should be used with caution. AZD2811 has been 
shown to be an inhibitor of MATE1 and MATE2K transporters. A drug interaction with 
substrates of either transporter cannot be ruled out, the most important substrate known to date 
being metformin.
Preclinical data suggests that AZD2811 is a substrate for BCRP. To allow for accurate 
assessment of the safety of the combination of AZD2811 and durvalumab, clinical inhibitors 
of BCRP (curcumin, cyclosporine A, eltrombopag) are not permitted in the first six patients in 
the trial that form part of the safety run-in group.
6.5.2.2
Prohibited Concomitant Medication and Treatments for Durvalumab
Prohibited concomitant medication and treatments for durvalumab are presented in Table 15.

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Table 15
Prohibited concomitant medications for durvalumab
Prohibited medication/class of drug:
Usage:
Any investigational anticancer therapy other than 
those under investigation in this study
Should not be given concomitantly while the participant is 
on study treatment
mAbs against CTLA-4, PD-1, or PD-L1 other than 
those under investigation in this study
Should not be given concomitantly while the participant is 
on study treatment
Any concurrent chemotherapy, radiotherapy, 
immunotherapy, or biologic or hormonal therapy for 
cancer treatment other than those under 
investigation in this study
Should not be given concomitantly while the participant is 
on study treatment. (Concurrent use of hormones for non-
cancer-related conditions [e.g., insulin for diabetes and 
hormone replacement therapy] is acceptable. Local 
treatment of isolated lesions, excluding target lesions, for 
palliative intent is acceptable [e.g., by local surgery or 
radiotherapy])
Live attenuated vaccines 
Should not be given from 90 days before through 90 days 
after the last dose of study intervention
Immunosuppressive medications, including but not 
limited to, systemic corticosteroids at doses 
exceeding 10 mg/day of prednisone or equivalent, 
methotrexate, azathioprine, and tumor necrosis 
factor-α blockers
Should not be given concomitantly, or used for 
premedication prior to the IP infusions. The following are 
allowed exceptions:
Use of immunosuppressive medications for the 
management of IP-related AEs, 
Use in participants with contrast allergies. 
In addition, use of inhaled, topical, and intranasal 
corticosteroids are permitted.
A temporary period of steroids will be allowed if clinically 
indicated and considered to be essential for the 
management or prevention of nonimmunotherapy related 
events experienced by the participant (e.g., chronic 
obstructive pulmonary disease, radiation, nausea, etc)
EGFR TKIs
Should not be given concomitantly 
Should be used with caution in the 90 days post last dose of 
durvalumab
Increased incidences of pneumonitis (with third generation 
EGFR TKIs) and increased incidence of transaminase 
increases (with firstgeneration EGFR TKIs) has been 
reported when durvalumab has been given concomitantly

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Table 15
Prohibited concomitant medications for durvalumab
Prohibited medication/class of drug:
Usage:
Herbal and natural remedies that may have 
immune-modulating effects and interfere with 
interpretation of study results
Must not be given concomitantly unless agreed by the 
Sponsor
AE = adverse event; CTLA-4 = cytotoxic T-lymphocyte-associated protein 4; EGFR = epidermal growth factor 
receptor; IP = investigational product; mAb = monoclonal antibody; PD-1 = programmed cell death-protein 1; 
PD-L1 = programmed death-ligand 1; TKI = tyrosine kinase inhibitor.
6.5.3
Drug-drug Interactions
6.5.3.1
AZD2811 Drug-drug Interactions
AZD2811 is an investigational drug for which no data on in vivo interactions are currently
available. Based on in vitro data and clinical exposure data, AZD2811 is considered unlikely 
to cause clinically significant drug interactions through inhibition or induction of cytochrome 
P450 enzyme activity. In vitro data have, however, also shown that the principal enzyme 
responsible for the metabolism of AZD2811 is CYP3A4.  
6.5.3.2
Durvalumab Drug-drug Interactions
There is no information to date on drug-drug interactions with durvalumab either non-
clinically or in patients. As durvalumab is a mAb and therefore a protein, it will be degraded 
to small peptides and amino acids and will be eliminated by renal and reticuloendothelial 
clearance. It is therefore not expected that durvalumab will induce or inhibit the major drug 
metabolizing cytochrome P450 pathways. As a result, there are no expected PK drug-drug 
interactions. The mechanism of action of durvalumab involves binding to PD-L1, and 
therefore significant pharmacodynamic drug interactions with the commonly administered 
concomitant medications are not expected. Despite this, appropriate clinical monitoring will 
be conducted to evaluate any potential drug-drug interactions.
6.5.4 Rescue Medicine
As a result of immune-mediated AEs (imAEs) that could potentially be experienced by 
patients on durvalumab, steroids, and other immunosuppressant rescue medication, has to be 
made available to this patient population. The 2 products that fall into the category of 
immunosuppressants are infliximab (e.g., for colitis) and mycophenolate (e.g., for hepatitis). 
Generic/biosimilar versions of rescue drugs are allowable if approved in the treating country. 
AstraZeneca supply chain will be responsible for sourcing these 2 rescue medications to the 
sites if local regulations prevent the use of infliximab and mycophenolate in this indication, as 
they are considered off-label for management of immunotherapy-related toxicities. These 
rescue medications must be receipted, controlled, and dispensed by the unblinded pharmacist 
(if supplied centrally) and stored according to the labelled storage conditions, with 

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temperature excursions reported accordingly by the unblinded pharmacist. If required for use 
as a result of an imAE, then the IXRS will provide to the pharmacists the kit identification 
number to be allocated to the participant at the time. 
6.6
Dose Modification
6.6.1
Dose Modification for AZD2811
Substantial acute toxicities should be managed as medically indicated and with temporary 
suspension of AZD2811, as appropriate. Dose reductions and/or holds and initiations of 
supportive care are allowed as clinically indicated by the treating physician (Section 8.5.2).
The starting dose of AZD2811 is 
 to be given every 
 with GCSF on/from 
 
. Dosing and dose adjustments are shown in Table 16.
Table 16
Dose Modification for AZD2811
Dose level
Agent and Dose
Route
Duration
Observation Time
Schedule
Dose level 1
AZD2811 
IV
 
 
 
 
 
 
Dose level -1
AZD2811 
IV
 
 
 
 
 
 
 
Dose level -2
AZD2811 
IV
 
 
 
 
 
 
 
IV = intravenous; 
.
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6.6.2
Dose Modification for Durvalumab
Dose delays are permitted (see Dosing Modification and Toxicity Management Guidelines 
referenced in Section 8.5.2). However, dose reduction of durvalumab is not permitted. If a 
cycle is prolonged due to toxicity, this should still be counted as one cycle. A cycle will be 
counted if treatment is started even if the full dose is not delivered. Dosing may be delayed 
due to either an immune or a non-immune-related AE. If dosing must be delayed for reasons 
other than treatment-related toxicity, dosing will resume as soon as feasible. The durvalumab 
dose may be delayed for up to a maximum of 12 weeks from initiation of corticosteroids; see 
Section 8.5.2 for additional details.
6.6.3
Dose Modification of Platinum-based Chemotherapy, Cisplatin, and/or 
Carboplatin
Dose modification of EP-based chemotherapy, cisplatin, and/or carboplatin will be according 
to the package insert and local SOC. 
6.7
Intervention After the End of the Study
Participants, having reached the end of study, should be followed according to Section 1.3. 
See also Section 7.1.
7
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL
7.1
Discontinuation of Study Intervention
If either durvalumab or AZD2811 administration is to be permanently discontinued, 
administration of the other study intervention may continue as monotherapy if the investigator 
considers that the participant will gain benefit. If participants are receiving durvalumab 
monotherapy, the schedule of activities may be reduced to Day 1 visits and assessments only. 
Scans must be performed at the frequency stated in the SoA.
It may be necessary for a participant to permanently discontinue all study intervention. If 
study intervention is permanently discontinued, the participant will remain in the study to be 
evaluated for safety assessment (until resolution or absence of improvement), as well as for 
disease progression and/or death, whichever occurs first. See the SoA (Table 4) for data to be 
collected at the time of discontinuation of study intervention and follow-up, and for any 
further evaluations that need to be completed.
Note that discontinuation from study intervention is NOT the same thing as a withdrawal from 
the study or end of study. 

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An individual participant will not receive any further study intervention if any of the 
following occur in the participant in question:
!
Withdrawal of consent from further treatment with study intervention. The participant is, 
at any time, free to discontinue treatment, without prejudice to further treatment. 
Withdrawal from study intervention treatment does not mean withdrawal from study, and 
the participant is normally expected to continue to participate in the study (e.g., for safety 
and survival follow-up). If they specifically withdraw their consent to all further 
participation in any study procedures and assessments (see Section 7.3), then they will be 
withdrawn from the study.
!
An AE that, in the opinion of the investigator or AstraZeneca, contraindicates further 
dosing.
!
Any AE that meets criteria for discontinuation as defined in the Dosing Modification and 
Toxicity Management Guidelines (see Section 8.5).
!
Pregnancy or intent to become pregnant.
!
Non-compliance with the study protocol that, in the opinion of the investigator or 
AstraZeneca, warrants withdrawal from treatment with study intervention (e.g., refusal to 
adhere to scheduled visits).
!
Initiation of alternative anticancer therapy including, or not, another investigational agent. 
!
Clinical progression and investigator determination that the participant is no longer 
benefiting from treatment with study intervention.
!
Confirmed radiological progression (refer to Appendix F).
See the SoA (Section 1.3) for data to be collected at the time of intervention discontinuation 
and follow-up, and for any further evaluations that need to be completed.
7.1.1
Re-treatment Following Relapse
A participant who has been treated for a minimum of 2 years and continues to experience CR, 
PR, or SD, as demonstrated by radiographic measures, may be considered for treatment 
discontinuation. Data from other immunotherapy studies suggest that patients who initially 
derive clinical benefit from immunotherapy can derive benefit again once the subject has PD 
while off therapy (Hamid et al, 2013; Wolchok et al, 2013).
Participants who progress during the first 52 weeks after the last dose of study treatment will 
be eligible for retreatment with the combination of AZD2811 and durvalumab (same dose and
schedule as at the time of discontinuation) after consultation with, and in agreement with, the 
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agent(s) as appropriate for the participants at the time of retreatment. The exclusion criteria 
listed below must not apply:
1
Meets any of the study intervention discontinuation criteria (Section 7.1);
2
ECOG performance status (PS) > 2;
3
Rapid PD or threat to vital organs/critical anatomical sites (e.g., spinal cord compression) 
requiring urgent alternative medical intervention;
4
Participant has had severe/refractory imAE or development of new autoimmune condition 
that, in the opinion of the investigator, poses undue risk to the participant.
5
Participant has received any other anticancer treatment for their disease following initial 
study intervention discontinuation
This option for retreatment will be limited to one occasion, and will apply only if the study 
protocol is still active, ie, the final database lock has not yet occurred. The participant will 
need to follow the SoA as described in Section 1.3. Participants must also be reconsented.  
7.2
Participant Withdrawal from the Study
!
A participant may withdraw from the study at any time at his/her/their own request, or 
may be withdrawn at any time at the discretion of the investigator for reasons including,
but not limited to, safety, behavioral, and/or compliance. This is expected to be 
uncommon.
!
A participant who considers withdrawing from the study must be informed by the 
investigator about modified follow-up options (e.g., telephone contact, a contact with a 
relative or treating physician, or information from medical records). Documentation of the 
scope of withdrawal and follow-up permissions must be clearly documented in the source. 
The Global Study Team should be informed.  
!
If the participant withdraws consent for disclosure of future information, the Sponsor may 
retain and continue to use any data collected up to the date of withdrawal of consent.
!
If a participant withdraws from the study, it should be confirmed if he/she still agrees for 
existing samples to be used in line with the original consent. If he/she requests withdrawal 
of consent for use of samples, destruction of any samples taken and not tested should be 
carried out in line with what was stated in the informed consent and local regulation. The 
investigator must document the decision on use of existing samples in the site study 
records and inform the Global Study Team.
7.3
Lost to Follow-up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.

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The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:
!
The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible, counsel the participant on the importance of maintaining the assigned visit 
schedule, and ascertain whether or not the participant wishes to and/or should continue in 
the study.
!
Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant. Where possible, 3 telephone calls and, 
if necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods. These contact attempts should be documented in the participant’s 
medical record.
!
Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study.
!
Site personnel, or an independent third party, will attempt to collect the vital status of the 
participant within legal and ethical boundaries for all participants enrolled into the study,
including those who did not get study intervention. Public sources may be searched for 
vital status information. If vital status is determined as deceased, this will be documented 
and the participant will not be considered lost to follow-up. Sponsor personnel will not be 
involved in any attempts to collect vital status information. 
Discontinuation of specific sites, or of the study as a whole, are handled as part of 
Appendix A.
8
STUDY ASSESSMENTS AND PROCEDURES
A Web-Based Data Capture system will be used for data collection and query handling. The 
investigator will ensure that data are recorded on the eCRFs as specified in this study protocol 
and in accordance with the instructions provided. The investigator ensures the accuracy, 
completeness, and timelines of the data recorded and the provision of answers to data queries 
according to the Clinical Study Agreement (CSA). The investigator will sign the completed 
eCRFs. A copy of the completed eCRFs will be archived at the study site.
!
Study procedures and their timing are summarized in the SoA. Protocol waivers or 
exemptions are not allowed unless in the event of a civil crisis, natural disaster, or public
health crisis (see Section 4.1.5 and Appendix H).
!
Immediate safety concerns should be discussed with the Sponsor immediately upon 
awareness to determine if the participant should continue or discontinue study 
intervention, or if other actions are required.

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!
Adherence to the study design requirements, including those specified in the SoA, are 
required for study conduct.
!
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
!
Procedures conducted as part of the participant’s routine clinical management (e.g., blood 
count) and obtained before signing of the ICF may be utilized for screening or baseline 
purposes, provided the procedures met the protocol-specified criteria and were performed 
within the time frame defined in the SoA.
!
The maximum amount of blood collected from each participant over the duration of the 
study, including any extra assessments that may be required, will be approximately 
100 mL at screening and will not exceed approximately 430 mL during any 8 week period 
whilst on study treatment. Repeat or unscheduled samples may be taken for safety reasons 
or for technical issues with the samples.
8.1
Efficacy Assessments
Given the decision on 14 December 2021 to terminate enrolment, the abbreviated CSR will 
focus on reporting of safety endpoints. Therefore, the efficacy analyses will be streamlined
(see Section 9.4.2 for further detail) and this will be fully documented in the SAP. Sections 
from CSP v8.0 are retained below for reference.
This study will evaluate the primary endpoint of proportion of participants alive and 
progression free at 12 months (APF12) from first dose of study therapy in the induction phase, 
who have moved to the maintenance phase. Secondary efficacy assessments are of proportion 
of participants alive at 12, 15, and 18 months from first dose of study therapy in the induction 
phase (OS12, OS15, and OS18), proportion of participants alive and progression free at 6 
months and 9 months from first dose of study therapy in the induction phase (APF6, APF9), 
OS from the first dose of study therapy in the induction phase, PFS from first dose of study 
therapy in the induction phase, and objective response rate (ORR) from first dose of study 
therapy. The PFS and ORR endpoints will be derived (by AstraZeneca) from site investigator 
assessment, according to RECIST v1.1. The primary and secondary endpoints will be assessed 
for participants who enter the maintenance phase. The ORR will also be assessed for all 
participants in the induction phase and for the participants who enter the maintenance phase.
From CSP v8.0, the starting dose of AZD2811 in the maintenance phase will be 
, the 
study will therefore primarily report efficacy for the 
 dose. Due to early termination of 
enrolment, CSPv8 was never implemented and no new patients started treatment with 
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AZD2811; all new patients transitioning into the maintenance phase were treated with 
durvalumab monotherapy. Further sensitivity analyses will be defined in the SAP.
Tumor assessments utilize images from CT (preferred) or MRI, each preferably with IV 
contrast, of the chest, abdomen, and pelvis, collected during screening/baseline and at regular 
(follow-up) intervals during study treatment. Any other areas of disease involvement should 
be additionally imaged based on the signs and symptoms of individual participants. 
The RECIST v1.1 guidelines (Appendix F) provide a method of assessment of change in
tumor burden in response to treatment. Screening/baseline imaging should be performed no 
more than 28 days before Cycle 1 Day 1 while another one will need to be ensured in the third 
week of 
 of the induction therapy. Only participants with a RECIST response of CR, 
PR, or SD will enter the maintenance phase (CR or PR does not need to be confirmed). The 
RECIST v1.1 assessments of baseline images identify target (defined measurable) and non-
target lesions (NTLs), and each lesion (and any new lesion) is evaluated in subsequent, on-
treatment follow-up images. This allows determination of follow-up target lesion (Hassel et 
al) response, NTL response, and overall time point tumor responses (CR, PR, SD, PD, or not 
evaluable [NE]). The methods of assessment used at baseline should be used at each 
subsequent follow-up assessment.
From the investigator’s review of the imaging scans, the RECIST tumor response data will be 
used to determine each participant’s visit response according to RECIST v1.1. At each visit, 
participants will be programmatically assigned a RECIST v1.1 visit response of CR, PR, SD, 
or PD, using information from TLs, NTLs, and new lesions, and depending on the status of 
their disease compared with baseline and previous assessments. If a participant has had a 
tumor assessment that cannot be evaluated, then the participant will be assigned a visit 
response of NE unless there is evidence of progression, in which case the response will be 
assigned as PD. Please refer to Appendix F for additional detail on RECIST.
Efficacy will be assessed on images collected 
± 1 week for the first 36 weeks relative to 
the date of first dose of study intervention in the induction period, and 
 ± 1 week 
thereafter until confirmed objective disease progression or the participant is off-study. It is 
important to follow the assessment schedule as closely as possible (refer to the SoAs in 
Table 1, Table 3 , and Table 4). Where possible, every effort should be made to schedule the 
scan within 1 week prior to dosing with AZD2811; scan results MUST be reviewed prior to 
dosing to confirm the absence of disease progression. If disease progression is suspected, an 
unscheduled imaging assessment should be performed. If an unscheduled imaging assessment 
is performed and the participant has not progressed, every attempt should be made to perform 
the subsequent assessments at his or her next regularly scheduled imaging visit.
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AstraZeneca requests that at least one subsequent scan is acquired after each initial 
progression event for all participants, across all arms of the study, no earlier than 4 weeks 
after and no later than the next regularly scheduled imaging visit after the initial progression 
event.
If a participant discontinues treatment (and/or receives a subsequent anticancer therapy) after 
the initial assessment of clinical progression, then the participant should continue to be 
followed with scheduled imaging until objective disease progression. 
Following objective disease progression, participants should continue to be followed up for 
survival every 2 months (8 weeks) as outlined in the follow-up SoA (Table 4); this may be 
done via telephone contact. In addition, all participants will be contacted in the week 
following DCO to confirm survival status.
8.1.1
Reading of Scans
Although scan assessments will be performed by investigators, all images, including 
unscheduled visit scans, will be collected on an ongoing basis and sent to an AstraZeneca-
appointed imaging Contract Research Organization for quality control and storage in the event 
that central review is required. Management of participants will be based solely upon the 
results of the RECIST v1.1 assessment conducted by the investigator. 
8.1.2
Survival Assessments
Assessments for survival must be made every 2 months following treatment discontinuation. 
Survival information may be obtained via telephone contact with the participant or the 
participant’s family, or by contact with the participant’s current physician. The details of first 
and subsequent therapies for cancer, after discontinuation of treatment, will be collected.  
8.2
Safety Assessments
Planned time points for all safety assessments are provided in the SoA.
For participants starting the maintenance phase with durvalumab monotherapy, who 
subsequently receive AZD2811 in a later cycle (ie, beyond 
 additional safety 
assessments and PK sampling are required. For example, if a participant receives their first 
dose of AZD2811 in 
 all safety and PK assessments must be performed as if for 
Cycle 5. Additional safety assessments must be performed for the first  cycles of AZD2811 
treatment, and PK sampling must be completed for the first  cycles of AZD2811 treatment 
(following the SoA for Cycles 
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8.2.1
Physical Examinations
!
A full physical examination will be performed and include assessments of the following: 
General appearance, respiratory, cardiovascular, abdomen, skin, head and neck (including 
ears, eyes, nose, and throat), lymph nodes, thyroid, muscular-skeletal (including spine and 
extremities), and routinely performed neurological exam. 
!
A targeted physical examination will be based on symptoms and will include, at a 
minimum, assessments of the regions considered abnormal at study entry and those 
indicated by clinical observation. Special attention should be paid to participants with 
skin abnormalities in their medical history and/or observed at baseline, as well as 
abnormalities appearing during trial treatment. Any skin changes should be assessed and 
documented throughout the study. 
Physical examination will be performed at time points as specified in the SoA and will need 
special attention for skin alteration if observed at study entry. Situations in which physical 
examination results should be reported as AEs are described in Section 8.3.5.
8.2.2
Vital Signs
Vital signs will be performed at timelines as specified in the SoA.
Vital signs (blood pressure (systolic/diastolic), pulse rate, body temperature, and respiration 
rate) will be evaluated according to the assessment schedules (Section 1.3). Body weight is 
also recorded at each visit, along with vital signs.
Height should be collected at screening only. 
Situations in which vital signs results should be reported as AEs are described in 
Section 8.3.5. For any AEs of infusion reactions, please enter the vital signs values into the 
case report form.
8.2.3
Electrocardiograms
An electrocardiogram (ECG) will be performed at time points as specified in the SoA. 
Electrocardiograms should be obtained after the participant has been in a supine position for 
5 minutes and recorded while the participant remains in that position. Resting 12-lead ECGs 
will be recorded at screening and as clinically indicated throughout the study (see 
Section 1.3). All participants will have triplicate 12-lead ECGs (about 5 minutes apart). The 
ECG needs to be performed prior to the onset of the IV therapy (AZD2811 + durvalumab) and 
approximately 15 minutes after the end of all IV therapies.
During Induction, if there are clinically relevant cardiac observations during an infusion, 
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(approximately 15 minutes of the end of infusion) should be performed at all subsequent 
infusions.
During Maintenance, if there are clinically relevant cardiac observations during an infusion, 
triplicate 12-lead ECGs (about 5 minutes apart) pre- and post-AZD2811 and pre- and post-
durvalumab infusion (approximately 15 minutes of the end of infusion) should be performed 
at all subsequent infusions.
In case of clinically significant ECG abnormalities, including a Fridericia’s Correction 
Formula (QTcF) value > 470 ms, 2 additional 12-lead ECGs should be obtained over a brief 
period, at 15 and 30 minutes, to confirm the finding. Sites may also report Bazett’s Correction 
Formula (QTcB) if that is the local standard. 
Situations in which ECG results should be reported as AEs are described in Section 8.3.5.
8.2.4
Clinical Safety Laboratory Assessments
Blood and urine samples for determination of clinical chemistry, hematology, urinalysis, and 
other safety tests will be taken at the times indicated in the assessment schedules and as 
clinically indicated (see Section 1.3). 
Clinical laboratory safety tests, including serum pregnancy tests, will be performed in a 
licensed clinical laboratory according to local standard procedures. Sample tubes and sample 
sizes may vary depending on the laboratory method used and routine practice at the site. Urine 
pregnancy tests may be performed at the site using a licensed test (urine or serum pregnancy 
test). Clinically significant abnormal laboratory results should be repeated as soon as possible 
(preferably within 24 to 48 hours) unless they are in line with previous assessments.
Additional safety samples may be collected if clinically indicated at the discretion of the 
investigator. The date, time of collection, and results (values, units, and reference ranges) will 
be recorded on the appropriate eCRF.
The laboratory variables to be measured are presented in Table 17 (clinical chemistry), 
Table 18 (hematology), Table 19 (urinalysis), and Table 20 (other safety tests).
Other safety tests to be performed at screening include assessment for HbsAg, hepatitis C 
antibodies, and HIV antibodies. Tuberculosis test will be performed as per Institutional 
Guidelines at screening.

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Table 17
Clinical Chemistry
Albumin
Lipaseb
Alkaline phosphatasea
Magnesiumd
ALTa
Potassium
Amylaseb
Sodium
ASTa
Total bilirubina
Bicarbonatec
Total protein
Calcium
TSH
Chloridec
T3 free(reflex)
Creatinine clearance
T4 free(reflex)
C-reactive proteine
Urea or blood urea nitrogen, depending on local practice
Creatinine
Carbon Dioxidec
Gamma glutamyl transferase
Glucose
Lactate dehydrogenase
a
Tests for ALT, AST, alkaline phosphatase, and total bilirubin must be conducted and assessed concurrently. 
If total bilirubin is ≥2 × upper limit of normal (and no evidence of Gilbert’s syndrome), then fractionate 
into direct and indirect bilirubin.
b
It is preferable that both amylase and lipase parameters are assessed. For sites where only one of these 
parameters is routinely measured, either lipase or amylase is acceptable.
c
Bicarbonate should be performed where standard. Carbon dioxide may be performed in place of 
bicarbonate, where standard.
d
Magnesium required at screening and Cycle 1 Day 1, and then should be performed only as clinically 
indicated or per local practice. 
e
Not required at all time points; refer to the Schedule of Activities tables in Section 1.3
AE = Adverse event; ALT = Alanine aminotransferase; AST = Aspartate aminotransferase; 
T3 = Triiodothyronine; T4 = Thyroxine; TSH = Thyroid-stimulating hormone.
Table 18
Hematology
Full White Blood Cell Count Differential: Neutrophils, 
Lymphocytes, Monocytes, Eosinophils, Basophilsa
Red Blood Cells
Hematocrit
Hemoglobin
Platelet count
HbA1c (baseline only)
Total white cell count
Reticulocytes a
a
Can be recorded as absolute counts or as percentages. Absolute counts will be calculated by data 
management if entered as percentage. Total white cell count therefore has to be provided.

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Table 19
Urinalysis
Bilirubin
Ketones
Blood
pH
Color and appearance
Protein
Glucose
Specific gravity
Note: Microscopy should be used as appropriate to investigate white blood cells and use the high-power field for 
red blood cells.
Table 20
Other Safety Tests
Coagulation Tests: prothrombin time, partial prothrombin time, international normalized ratio, fibrinogen.
HbsAg, hepatitis C antibodies, and HIV antibodies
Tuberculosis test is required at screening; method of testing will be according to Institutional Guidelines
Pregnancy test: Women of Childbearing Potential Only; serum is required at screening and within 3 days of 
Cycle 1 Day 1; urine may be used at future visits. Pregnancy testing will be performed monthly (28 +/- 7 days) 
through 90 days post last dose or until a new treatment is initiated, whichever is shorter. 
If a participant shows an AST or ALT ≥3 × ULN together with TBL ≥2 × ULN, refer to 
Appendix E for further instructions on cases of increases in liver biochemistry and evaluation 
of HL. These cases should be reported as SAEs if, after evaluation, they meet the criteria for a 
Hy’s law case or if any of the individual liver test parameters fulfill any of the SAE criteria. 
All participants meeting the criteria for HL should have further chemistry profiles performed 
at 28 days (± 3 days), 2 months (± 1 week), and 3 months (± 1 week) after permanent 
discontinuation of IP (see Appendix E).
After completion of Cycle 1, a new cycle of treatment may begin when the absolute neutrophil 
count (ANC) is ≥1.5 × 109/L and the platelet count is ≥75 × 109/L, and any other clinically 
relevant adverse effects have resolved or reverted to baseline. The next cycle may be delayed 
up to 14 days until ANC is ≥1.5 × 109/L, and the platelet count is ≥75 x 109/L or returned to 
baseline (see Section 8.5.1). 
Any clinically significant abnormal laboratory values should be repeated as clinically 
indicated and the date, time of collection, and results (values, units, and reference ranges) 
should be recorded on the appropriate eCRF.
Situations in which laboratory safety results should be reported as AEs are described in 
Section 8.3.5.
All participants with Grade 3 or 4 laboratory values at the time of completion or 
discontinuation from study treatment must have further tests performed until the laboratory 

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values have returned to Grade 1 or 2, unless these values are not likely to improve because of 
the underlying disease.
8.2.5
Early Participant Review for Safety
Participants will be evaluated 15 days after the first dose of each cycle of chemotherapy and 
on Days 8 and 15 of each maintenance cycle to ensure early identification and management of 
toxicities by the investigator. Participants will also be evaluated on Day 12 of Cycles 
 
(the first  cycles of AZD2811 treatment).
8.2.6
WHO ECOG Performance Status
World Health Organization ECOG PS will be assessed at the times specified in the assessment 
schedules (see Section 1.3), based on the following:
0
Fully active; able to carry out all usual activities without restrictions.
1
Restricted in strenuous activity but ambulatory and able to carry out light work or work of 
a sedentary nature (e.g., light housework or office work).
2
Ambulatory and capable of self-care but unable to carry out any work activities; up and 
about more than 50% of waking hours.
3
Capable of only limited self-care; confined to bed or chair more than 50% of waking 
hours.
4
Completely disabled; unable to carry out any self-care and totally confined to bed or 
chair.
5
Dead.
8.2.7
Other Safety Assessments
If new or worsening pulmonary symptoms (e.g., dyspnea) or radiological abnormality 
suggestive of pneumonitis/ILD is observed, toxicity management as described in detail in the 
Toxicity Management Guidelines will be applied. The results of the full diagnostic workup 
(including high-resolution computed tomography [HRCT], blood and sputum culture, 
hematological parameters, etc) will be captured in the eCRF. It is strongly recommended to 
perform a full diagnostic workup, to exclude alternative causes such as lymphangitic 
carcinomatosis, infection, allergy, cardiogenic edema, or pulmonary hemorrhage. In the 
presence of confirmatory HRCT scans where other causes of respiratory symptoms have been 
excluded, a diagnosis of pneumonitis (ILD) should be considered and the Toxicity 
Management Guidelines should be followed.  
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Pneumonitis (ILD) Investigation 
The following assessments, and additional assessments if required, will be performed to 
enhance the investigation and diagnosis of potential cases of pneumonitis. The results of the 
assessment will be collected.
!
Physical examination
∀
Signs and symptoms (cough, shortness of breath, and pyrexia, etc.), including 
auscultation for lung field, will be assessed
!
SpO2
∀
Saturation of peripheral oxygen (SpO2)
!
Other items
∀
When pneumonitis (ILD) is suspected during study treatment, the following markers 
should be measured, where possible:
o
ILD markers (KL-6, SP-D) and β-D-glucan
o
Tumor markers: Particular tumor markers, which are related to disease 
progression  
o
Additional Clinical chemistry: CRP, lactate dehydrogenase
8.3
Adverse Events and Serious Adverse Events
The PI is responsible for ensuring that all staff involved in the study are familiar with the 
content of this section.
The definitions of an AE or SAE can be found in Appendix B.
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant’s legally authorized representative). 
The investigator and any designees are responsible for detecting, documenting, and recording 
events that meet the definition of an AE.
8.3.1
Time Period and Frequency for Collecting AE and SAE Information
Adverse events, including SAEs, will be collected from time of signing the ICF throughout 
the treatment period and including the follow-up period (90 days after the last dose of study 
intervention) as specified in the SoA (see Section 1.3).
If the investigator becomes aware of an SAE with a suspected causal relationship to the IP that 
occurs after the end of the clinical study in a participant, the investigator shall, without undue 
delay, report the SAE to the Sponsor.

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8.3.2
Follow-up of AEs and SAEs
Any AEs that are unresolved at the participant’s last visit in the study are followed up by the 
investigator for as long as medically indicated, but without further recording in the eCRF. 
AstraZeneca retains the right to request additional information for any participant with 
ongoing AE(s)/SAE(s) at the end of the study, if judged necessary.
Adverse Event Variables
The following variables will be collected for each AE:
!
AE (verbatim)
!
The date, and time where relevant, when the AE started and stopped
!
Initial and maximal CTCAE grade 
!
Assessment of seriousness 
!
Assessment of relatedness to the study intervention - AZD2811 and durvalumab
!
Action taken with regard to IP(s) as well as the use of supportive treatment
!
AE caused participant’s withdrawal from study (yes or no)
!
Outcome
In addition, the following variables will be collected for SAEs:
!
Date investigator became aware of SAE
!
Where applicable, dates of hospitalization and discharge
!
In the event of death, date of death, probable cause of death, autopsy performed with 
details 
!
Causality assessment in relation to study procedure(s)
!
Causality assessment to other medication
8.3.3 Causality Collection
The investigator should assess causal relationship between IP and each AE, and answer ‘yes’ 
or ‘no’ to the question ‘Do you consider that there is a reasonable possibility that the event 
may have been caused by the investigational product?’
For SAEs, causal relationship should also be assessed for other medication and study 
procedures. Note: For SAEs that could be associated with any study procedure, the causal 
relationship is implied as ‘yes’.
A guide to the interpretation of the causality question is found in Appendix B. 

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8.3.4 Adverse Events Based on Signs and Symptoms
All AEs spontaneously reported by the participant or care provider, or reported in response to 
the open question from the study site staff ‘Have you had any health problems since the 
previous visit/you were last asked?’, or revealed by observation, will be collected and 
recorded in the eCRF. When collecting AEs, the recording of diagnoses is preferred (when 
possible) to recording a list of signs and symptoms. However, if a diagnosis is known and 
there are other signs or symptoms that are not generally part of the diagnosis, the diagnosis 
and each sign or symptom will be recorded separately.
8.3.5 Adverse Events Based on Examinations and Tests
The results from the CSP-mandated laboratory tests and vital signs will be summarized in the 
Clinical Study Report (CSR). Deterioration as compared to baseline in CSP-mandated 
laboratory values, vital signs, ECGs, and clinical/neurological assessment(s) should therefore 
only be reported as AEs if they fulfil any of the SAE criteria, are the reason for 
discontinuation of treatment with the IP, or are considered to be clinically relevant as judged 
by the investigator (which may include, but not be limited to, consideration as to whether 
treatment or non-planned visits were required or other action was taken with the study 
intervention, e.g., dose adjustment or drug interruption).
If deterioration in a laboratory value/vital sign is associated with clinical signs and symptoms, 
the sign or symptom will be reported as an AE and the associated laboratory result/vital sign 
will be considered as additional information. Wherever possible, the reporting investigator 
uses the clinical, rather than the laboratory term (e.g., anemia versus low hemoglobin value). 
In the absence of clinical signs or symptoms, clinically relevant deteriorations in non-
mandated parameters should be reported as AE(s).
Deterioration of a laboratory value, which is unequivocally due to disease progression, should 
not be reported as an AE/SAE.
Any new or aggravated clinically relevant abnormal medical finding at a physical 
examination, as compared with the baseline assessment, will be reported as an AE unless 
unequivocally related to the disease under study (DUS).
8.3.6 Hy’s Law
Cases where a participant shows elevations in liver biochemistry may require further 
evaluation, and occurrences of AST or ALT ≥3 × ULN together with TBL ≥2 × ULN may 
need to be reported as SAEs. Please refer to Appendix E for further instruction on cases of 
increases in liver biochemistry and evaluation of HL.

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8.3.7 Disease Progression
Disease progression can be considered as a worsening of a participant’s condition attributable 
to the disease for which the IP is being studied. It may be an increase in the severity of the 
DUS and/or increases in the symptoms of the disease. The development of new, or 
progression of existing metastasis to the primary cancer under study, should be considered as 
disease progression and not an AE. Events, which are unequivocally due to disease 
progression, should not be reported as an AE during the study.
8.3.8 Disease Under Study
Symptoms of DUS are those which might be expected to occur as a direct result of SCLC. 
Events that are unequivocally due to DUS should not be reported as an AE during the study 
unless they meet SAE criteria or lead to discontinuation of the IP.
8.3.9
Reporting of Serious Adverse Events
All SAEs have to be reported, whether or not considered causally related to the IP or to the 
study procedure(s). All SAEs will be recorded in the eCRF.
If any SAE occurs in the course of the study, investigators or other site personnel will inform 
the appropriate AstraZeneca representatives within one day, ie, immediately, but no later 
than 24 hours of when he or she becomes aware of it.
The designated AstraZeneca representative will work with the investigator to ensure that all 
the necessary information is provided to the AstraZeneca Patient Safety data entry site within 
one calendar day of initial receipt for fatal and life-threatening events and within 5 calendar
days of initial receipt for all other SAEs.
For fatal or life-threatening AEs where important or relevant information is missing, active 
follow-up will be undertaken immediately. Investigators or other site personnel will inform
AstraZeneca representatives of any follow-up information on a previously reported SAE 
within one calendar day, ie, immediately, but no later than 24 hours of when he or she 
becomes aware of it.
Once the investigators or other site personnel indicate an AE is serious in the electronic data 
capture (EDC) system, an automated email alert is sent to the designated AstraZeneca 
representative.
If the EDC system is not available, then the investigator or other study site staff reports a SAE 
to the appropriate AstraZeneca representative by telephone.
The AstraZeneca representative will advise the investigator/study site staff how to proceed. 

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The reference document for definition of expectedness is the IB for AZD2811, the IB for 
durvalumab, and the local labels for etoposide, carboplatin, cisplatin, and G-CSF.
8.3.10
Pregnancy
All pregnancies and outcomes of pregnancy should be reported to AstraZeneca, except for:
!
If the pregnancy is discovered before the study participant has received any study 
intervention
8.3.10.1
Maternal Exposure
If a participant becomes pregnant during the course of the study, study intervention should be 
discontinued immediately.
Pregnancy itself is not regarded as an AE unless there is a suspicion that the IP under study 
may have interfered with the effectiveness of a contraceptive medication. Congenital 
abnormalities/birth defects and spontaneous miscarriages should be reported and handled as 
SAEs. Elective abortions without complications should not be handled as AEs. The outcome 
of all pregnancies (spontaneous miscarriage, elective termination, ectopic pregnancy, normal 
birth, or congenital anomaly) should be followed up and documented even if the participant 
was discontinued from the study.
If any pregnancy occurs in the course of the study, then the investigator or other site personnel 
informs the appropriate AstraZeneca representatives within 1 day, ie, immediately, but no 
later than 24 hours of when he or she becomes aware of it.
The designated AstraZeneca representative works with the investigator to ensure that all 
relevant information is provided to the AstraZeneca Patient Safety data entry site within 1 or 
5 calendar days for SAEs (see Section 8.3.9) and within 30 days for all other pregnancies.
The same timelines apply when outcome information is available.
When the eCRF module is used, include the following: The PREGREP module in the eCRF is 
used to report the pregnancy and the paper-based PREGOUT module is used to report the 
outcome of the pregnancy.
8.3.10.2
Paternal Exposure 
Male participants should refrain from fathering a child or donating sperm during the study and 
for 9 months after the last dose of AZD2811 and/or durvalumab, whichever is the longer time 
period. Please follow the local prescribing information relating to contraception.

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Pregnancy of the participant’s partner is not considered to be an AE. However, the outcome of 
all pregnancies (spontaneous miscarriage, elective termination, ectopic pregnancy, normal 
birth, or congenital anomaly) occurring from the date of the first dose until 90 days after the 
last dose of study intervention should, if possible, be followed up and documented.
Where a report of pregnancy is received, prior to obtaining information about the pregnancy, 
the investigator must obtain the consent of the participant’s partner. Therefore, the local study 
team should adopt the generic ICF template in line with local procedures and submit it to the 
relevant Ethics Committees/Institutional Review Boards prior to use.
Participants who are permanently discontinued from further receipt of study intervention, 
regardless of the reason, will be identified as having permanently discontinued treatment and 
will enter follow-up (see the SoAs [Table 4]).
8.3.11
Medication Error
If a medication error occurs in the course of the study, then the investigator or other site 
personnel informs the appropriate AstraZeneca representatives within 1 day, ie, immediately, 
but no later than 24 hours of when he or she becomes aware of it.
The designated AstraZeneca representative works with the investigator to ensure that all 
relevant information is completed within 1 (Initial Fatal/Life-Threatening or follow-up 
Fatal/Life-Threatening) or 5 (other serious initial and follow-up) calendar days if there is an 
SAE associated with the medication error (see Section 8.3.9) and within 30 days for all other 
medication errors.
The definition of a Medication Error can be found in Appendix B 4. 
8.3.12
Adverse Events of Special Interest
An AESI is one of scientific and medical interest specific to an understanding of the study 
intervention and may require close monitoring. An AESI may be serious or nonserious. The 
rapid reporting of AESIs allows ongoing surveillance of these events in order to characterize 
and understand them in association with the use of this study intervention.
8.3.12.1
AESIs for AZD2811
There are no AESIs currently identified for AZD2811.
8.3.12.2
AESIs for Durvalumab
Adverse events of special interest for durvalumab include, but are not limited to, events with a 
potential inflammatory or immune-mediated mechanism and which may require more 
frequent monitoring and/or interventions such as steroids, immunosuppressants, and/or 
hormone replacement therapy. These AESIs are being closely monitored in clinical studies 

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with durvalumab monotherapy and combination therapy. An imAE is defined as an AESI that 
is associated with drug exposure and is consistent with an immune-mediated mechanism of 
action and where there is no clear alternate etiology. Serologic, immunologic, and histologic 
(biopsy) data, as appropriate, should be used to support an imAE diagnosis. Appropriate 
efforts should be made to rule out neoplastic, infectious, metabolic, toxin, or other etiologic 
causes of the imAE. 
If the investigator has any questions with regard to an event being an imAE, the investigator 
should promptly contact the Study Physician.
Adverse events of special interest/imAEs observed with anti-PD-L/PD-1 agents, such as 
durvalumab, include pneumonitis, hepatitis, diarrhea/colitis, intestinal perforation, 
endocrinopathies (hypo- and hyper-thyroidism, adrenal insufficiency, 
hypophysitis/hypopituitarism, and Type 1 diabetes mellitus), nephritis, rash/dermatitis, 
myocarditis, myositis/polymyositis, pancreatitis, and rare/less frequent imAEs, including 
neuromuscular toxicities, such as myasthenia gravis, and Guillain-Barre syndrome.
Other inflammatory responses that are rare/less frequent with a potential immune-mediated 
etiology include, but are not limited to, pericarditis, sarcoidosis, uveitis, and other events 
involving the eye, skin, hematological, rheumatological events, vasculitis, non-infectious 
meningitis, and non-infectious encephalitis. It is possible that events with an inflammatory or 
immune-mediated mechanism could occur in nearly all organs.
In addition, infusion-related reactions and hypersensitivity/anaphylactic reactions with a 
different underlying pharmacological etiology are also considered AESIs.
Further information on these risks (e.g., presenting symptoms) can be found in the current 
version of the durvalumab IB. More specific guidelines for their evaluation and treatment are 
described in detail in the Dose Modification and Toxicity Management Guidelines (see 
Section 8.5.2). These guidelines have been prepared by the Sponsor to assist the investigator 
in the exercise of his/her clinical judgment in treating these types of toxicities. These 
guidelines apply to AEs considered causally related to the study drug/study regimen by the 
reporting investigator.
8.4
Overdose
For guidance, refer to AstraZeneca standard operating procedure: Reporting of Individual 
Safety Events in Clinical Studies. 
For this study, any dose of study intervention greater than the doses shown in Table 12 and 
Table 11 (or reduced, as indicated in Table 21 and Table 22), given 
 will be considered 
an overdose.
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!
An overdose with associated AEs is recorded as the AE diagnosis/symptoms on the 
relevant AE modules in the eCRF and on the Overdose eCRF module
!
An overdose without associated symptoms is only reported on the Overdose eCRF 
module
If an overdose on an AstraZeneca study intervention occurs in the course of the study, the 
investigator or other site personnel inform appropriate AstraZeneca representatives 
immediately, but no later than 24 hours of when he or she becomes aware of it.
The designated AstraZeneca representative works with the investigator to ensure that all 
relevant information is provided to the AstraZeneca Patient Safety data entry site within 1 or 
5 calendar days for overdoses associated with an SAE (see section 8.3.9) and within 30 days
for all other overdoses.
8.5
Management of Study Intervention-related Toxicities 
The following general guidance should be followed for management of toxicities.
!
Treat each of the toxicities with maximum supportive care (including holding the agent 
suspected of causing the toxicity, if required).
!
If the symptoms promptly resolve with supportive care, consideration should be given to 
continuing the same dose of the assigned study intervention along with appropriate 
continuing supportive care. If medically appropriate, dose modifications are permitted. 
!
All dose modifications should be documented with clear reasoning and the approach 
taken.
!
During the maintenance phase, if a participant needs to discontinue one of the study 
interventions, they may continue on study taking only the other study intervention.
All toxicities will be graded according to NCI CTCAE Version 5.0. 
8.5.1
Specific Toxicity Management and Dose Modification Information –
AZD2811
Substantial acute toxicities should be managed as medically indicated and with temporary 
suspension of AZD2811, as appropriate. Dose reductions and/or holds are allowed as 
clinically indicated by the treating physician, according to Table 21 and Table 22. AZD2811 
dosing should be delayed if there is any suspicion that a participant is suffering from an 
infection. In addition, there are certain circumstances in which AZD2811 should be 
permanently discontinued (Section 7.1).

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Dose reductions of AZD2811 should be considered if the toxicity is considered to be related to 
AZD2811. Dose re-escalation for individual participants is permitted on a case-by-case basis 
following discussion between the Study Physician and the investigator.
In general, if a participant experiences a Grade 1 or Grade 2 non-hematologic toxicity, no dose 
modification is required (except dose modifications for skin toxicities in Table 22). If a 
participant experiences a clinically significant and/or unacceptable toxicity not attributable to 
the disease or disease-related processes under investigation, dosing will be interrupted, or the 
dose reduced, and supportive therapy administered as suggested by the treating physician.
If the toxicity resolves or reverts to NCI CTCAE ≤ Grade 1 or baseline within 14 days of 
onset and the participant is showing clinical benefit, treatment with AZD2811 may be 
restarted using the rules below for dose modifications (see Table 21) and with discussion and 
agreement with the Study Physician as needed.
If any toxicity does not resolve to NCI CTCAE ≤ Grade 1 or baseline after 14 days (Day 35 of 
the cycle), then the participant should be withdrawn from AZD2811 treatment and observed 
until resolution of the toxicity (see Table 21). Any participant who develops a Grade 3 or 4 
non-hematologic toxicity that does not resolve to ≤ Grade 1 or baseline within 14 days should 
be removed from AZD2811 treatment unless approved by the Study Physician to continue 
treatment.
In the event of dose delays, the visit cycles will be calibrated such that Day 1 of each cycle is 
the date that the participant receives the dose.  

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Table 21
Dose Modification for Non-skin Toxicity
NCI CTCAE v5.0 Toxicity Grade
Action
For all toxicities leading to a dose hold, discontinue AZD2811 treatment if the toxicity does not resolve to NCI 
CTCAE ≤ Grade 1 or baseline after 14 days (ie, by Day 35 of a cycle), with exceptions noted below.
Non-Hematologic Toxicity
Grade 3 non-hematologic toxicity lasts > 4 but ≤7 
days and resolves to ≤ Grade 1 or baseline
•
At first occurrence, consider restarting at the 
same dose 
•
If second occurrence (≤ 7 days) Grade 3, reduce 
to dose level -1
•
If third time: Reduce to dose level -2 and discuss 
risk-benefit analysis with Study Physician
Toxicity remains Grade 3 > 7 days (despite supportive 
therapy) 
•
At first occurrence, reduce one dose level 
•
If second occurrence, reduce to dose level -2 and 
discuss risk-benefit analysis with Study Physician 
Grade 4 non-hematologic toxicity lasts> 4 but ≤7 days 
and resolves to ≤ Grade 1 or baseline 
•
At first occurrence, reduce to dose level -1
•
If second time: Discuss with Study Physician 
whether risk-benefit analysis supports 
continuation
Grade 4 non-hematologic toxicity lasts > 7 days
Discuss with Study Physician whether risk-benefit 
analysis supports continuation
Grade 3 or 4 non-hematologic toxicity that does not 
resolve to ≤ Grade 1 or baseline within 14 days
Discontinue study treatment unless approved by the 
Study Physician to continue
Sepsis, or any other Grade 3 or 4 non-hematological 
toxicity, not expected to be manageable/reversible 
with dose reduction
Discontinue study drug
Hematologic Toxicity
Participants can only be dosed with AZD2811 on Day 1 of any Cycle if the ANC is ≥ 1.5 × 109/L and the 
platelet count is ≥ 75 × 109/L.
Grade 0-3 (except as noted below)
Maintain dose
Grade 2-3 ANC; or 
Grade 2-3 thrombocytopenia without bleeding or 
requirement for platelet transfusion
•
Hold until recovery and then maintain dose
Grade 3 thrombocytopenia with bleeding or requiring 
a platelet transfusion; or 
Grade 4 ANC
•
First occurrence: Hold until recovery and then 
reduce to dose level -1
•
Second occurrence: Dose reduce to level -2 and 
discuss with Study Physician whether risk-benefit 
analysis supports continuation

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Table 21
Dose Modification for Non-skin Toxicity
NCI CTCAE v5.0 Toxicity Grade
Action
Febrile neutropenia; or
Grade 4 thrombocytopenia
•
First occurrence: Hold until recovery and then 
reduce to dose level -2
•
Second occurrence: Discontinue treatment
ANC = absolute neutrophil count; NCI CTCAE = National Cancer Institute Common Terminology Criteria for 
Adverse Events.
Skin Toxicity
Special attention should be paid to skin observation in participants having skin alterations in 
their medical history.
Participants will be monitored for appearance of pruritus and/or any signs of rash, including 
erythematous rash, exfoliative rash, maculo-papular rash, and skin exfoliation throughout 
study treatment. Participants experiencing skin toxicity should have the following dose 
modifications applied (see Table 22).

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Table 22
Dose Modification for Skin Toxicity
Toxicity
Occurrence
Action
Grade 1: Painless erythema, mild or localized 
pruritus, rash/acne intervention not indicated, 
rash/desquamation macular or papular eruption, 
or erythema without associated symptoms.
Any occurrence
Institute supportive measures, such as 
topical therapy for symptomatic relief, and 
continue therapy.
Grade 2: Painful erythema, intense or widespread 
pruritus, rash/acne intervention indicated, 
rash/desquamation macular or papular eruption 
with pruritus or other associated symptoms; 
localized desquamation or other lesions covering 
< 50% of BSA. Superficial ulceration < 2 cm; 
local wound care; medical intervention indicated.
Any occurrence
Institute supportive measures, such as 
topical therapy for symptomatic relief.  
Dose reduction or dose hold at the 
investigator’s discretion.
Participants requiring > 2 dose reductions 
will discontinue AZD2811.
Grade ≥3: Erythema with desquamation, pruritus 
intense or widespread interfering with ADL, 
rash/acne associated with pain requiring narcotic 
analgesics, ulceration or desquamation, 
rash/desquamation severe generalized 
erythroderma or macular or popular or vesicular 
eruption; desquamation covering ≥50% of BSA. 
Superficial ulceration ≥2 cm; local wound care; 
medical intervention indicated.
Any occurrence
Institute supportive measures, such as 
topical therapy for symptomatic relief, and 
interrupt AZD2811 until toxicity has 
resolved to Grade ≤1.
When resuming treatment after a dose 
interruption, if obtained within 3 weeks, 
reduce AZD2811 by one dose level. If 
toxicity has not returned to Grade ≤1 in 3 
weeks, treatment cannot be resumed 
without approval of the Sponsor.
Participants requiring > 2 dose reductions 
will discontinue AZD2811.
ADL = activities of daily living; BSA = body surface area.
8.5.2
Specific Toxicity Management and Dose Modification Information –
Durvalumab 
In territories where Durvalumab is approved for the treatment of ES-SCLC, toxicity 
management and dose modification should follow local recommendations (e.g. in the US 
follow the USPI). In territories where Durvalumab is not approved for the treatment of ES-
SCLC, toxicity management and dose modification should follow the Toxicity Management 
Guidelines (TMGs) described below and provided to the investigative site as an Annex 
document.
Comprehensive TMGs have been developed to assist investigators with the recognition and 
management of toxicities associated with the use of durvalumab. The TMGs provide 
information for the management of immune-mediated reactions, infusion-related reactions, 
and non-immune mediated reactions that may be observed with durvalumab, with specific 
instructions for dose modifications (including discontinuations) and treatment interventions. 

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Investigators are advised, however, to use local practice guidelines and consult local 
references for the management of toxicities observed with other cancer treatment. The most 
current version of the TMGs entitled “Dosing Modification and Toxicity Management 
Guidelines for Immune-Mediated, Infusion-Related, and Non-Immune Mediated Reactions 
(MEDI4736) Monotherapy or Combination Therapy with Tremelimumab or Tremelimumab 
Monotherapy” is provided to the investigative site as an Annex document and is maintained 
within the Site Master File. 
Participants should be thoroughly evaluated and appropriate efforts should be made to rule out 
neoplastic, infectious, metabolic, toxin, or other etiologic causes of the imAE. Serologic, 
immunologic, and histologic (biopsy) data, as appropriate, should be used to support an imAE
diagnosis. In the absence of a clear alternative etiology, events should be considered 
potentially immune related.
In addition, there are certain circumstances in which durvalumab should be permanently 
discontinued (see Section 7.1 of this protocol and the Dosing Modification and Toxicity 
Management Guidelines).
Following the first dose of study intervention, subsequent administration of durvalumab can 
be modified based on toxicities observed, as described in the Dosing Modification and 
Toxicity Management Guidelines. These guidelines have been prepared by the Sponsor to 
assist the investigator in the exercise of his/her clinical judgment in treating these types of 
toxicities. These guidelines apply to AEs considered causally related to durvalumab 
monotherapy regimen by the reporting investigator.
Dose reductions are not permitted. In case of doubt, the investigator should consult with the 
Study Physician.
8.6
Human Biological Samples
Instructions for the collection and handling of biological samples will be provided in the 
study -specific Laboratory Manual. Samples should be stored in a secure storage space with 
adequate measures to protect confidentiality. For further details on Handling of Human 
Biological Samples, see Appendix C.
Samples will be stored for a maximum of 15 years from the date of the issue of the CSR in 
line with consent and local requirements, after which they will be destroyed/repatriated. 
!
PK samples will be disposed of after the Bioanalytical Report finalization or 6 months 
after issuance of the draft Bioanalytical Report (whichever is earlier), unless consented 
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∀
PK samples may be disposed of or anonymized by pooling. Additional analyses may 
be conducted on the anonymized, pooled PK samples to further evaluate and validate 
the analytical method. Any results from such analyses may be reported separately 
from the CSR.
∀
Any residual back-up PK samples may be used for future exploratory biomarker 
research or diagnostic development related to cancer and/or drug action (in this case, 
residual back-up PK samples will be shipped to an AstraZeneca-assigned biobank –
see details in the Laboratory Manual) subject to optional participant consent.
8.6.1
Pharmacokinetics
!
Whole blood samples will be collected for measurement of whole blood concentrations of 
AZD2811 and metabolites, as specified in the SoA.
!
Serum samples will be collected for measurement of serum concentrations of 
durvalumab, as specified in the SoA.
!
Samples may be collected at additional time points during the study if warranted and 
agreed upon between the investigator and the Sponsor, e.g., for safety reasons. The timing 
of sampling may be altered during the course of the study based on newly available data 
(e.g., to obtain data closer to the time of peak or trough matrix concentrations) to ensure 
appropriate monitoring. 
!
Samples will be collected, labeled, stored, and shipped as detailed in the Laboratory 
Manual.
8.6.1.1
Determination of Drug Concentration
Samples for determination of drug concentration in whole blood (AZD2811 and metabolite) 
or serum (durvalumab) will be assayed by bioanalytical test sites operated by or on behalf of 
AstraZeneca, using an appropriately validated bioanalytical method. Full details of the 
analytical method used will be described in a separate Bioanalytical Report.
Incurred sample reproducibility analysis, if any, will be performed alongside the bioanalysis 
of the test samples. The results from the evaluation, if performed, will be reported in a 
separate Bioanalytical Report.
In addition, blood or plasma samples may be subjected to further analyses in order to 
investigate the released and/or encapsulated AZD2811, and other AZD2811 metabolites. 
These analyses, if any, will be reported outside of the CSR.

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8.6.2
8.6.2.1
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8.6.2.4
8.6.2.5
 
8.6.2.6
 
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8.7
8.8
Other Assessments
8.8.1
Patient-reported Outcomes
“PRO” is an umbrella term referring to all outcomes and symptoms that are directly reported 
by the participant. Patient-reported outcomes (PROs) have become a significant endpoint 
when evaluating effectiveness of treatments in clinical studies. The following PROs will be 
administered in this study: European Organization for Research and Treatment of Cancer
(EORTC) 30-item Core Quality of Life Questionnaire (QLQ-C30 v3; core questionnaire) and 
EORTC 13-item Lung Cancer Quality of Life Questionnaire (QLQ-LC13; lung cancer 
module) (see Appendix G).
The PRO instruments will be completed by the participants using a handheld electronic device 
(ePRO). All assessments should be completed without assistance from anyone according to 
the assessment schedules (see Section 1.3). It takes approximately 30 minutes for participants 
to complete the questionnaires; therefore, the burden to the participant is moderate. Paper may 
be used as a back up in the event that the electronic device cannot be used. 
8.8.1.1
EORTC QLQ-C30
The EORTC QLQ-C30 v3 questionnaire is included for the purpose of assessing health-
related quality of life (QoL), and is a well-established measure of health-related QoL/health 
status and commonly used as an endpoint in cancer clinical studies. The EORTC QLQ-C30 
consists of 30 questions that can be combined to produce 5 functional scales (physical, role, 
cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), 6 
individual items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial 
difficulties), and a global measure of health status (see Appendix G). The EORTC QLQ-C30 
will be scored according to the EORTC QLQ-C30 Scoring Manual (Fayers et al, 2001). An 
outcome variable consisting of a score from 0 to 100 will be derived for each of the symptom 
scales/symptom items, each of the function scales, and the global health status scale in the 
EORTC QLQ-C30 according to the EORTC QLQ-C30 Scoring Manual. Higher scores on the 
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global health status and functioning scales indicate better health status/function, but higher 
scores on symptom scales/items represent greater symptom severity.  
8.8.1.2
EORTC QLQ-LC13
For patients with SCLC, a disease-specific 13-item self-administered questionnaire for lung 
cancer was developed (EORTC QLQ-LC13; Appendix G) to be used in conjunction with the 
EORTC QLQ-C30 (Appendix G). It comprises both multi-item and single-item measures of 
lung cancer-associated symptoms (ie, coughing, hemoptysis, dyspnea, and pain) and side 
effects from conventional chemotherapy and radiotherapy (ie, hair loss, neuropathy, sore 
mouth, and dysphagia). Similar to the EORTC QLQ-C30, all questions except one have a 
4-point scale: “not at all”, “a little”, “quite a bit”, and “very much”. One question 
(number 43, “Did you take any medicine for pain?”) has a response option of “yes” or “no”. 
The scoring approach for the EORTC QLQ-LC13 is similar to the EORTC QLQ-C30.
8.8.2
Administration of the Patient-reported Outcome Questionnaires
Participants will complete the PRO assessments by using ePRO during clinic visits at the 
beginning of the visit. The assessment should be provided first, and should be completed 
before the participant sees the investigator or is aware of disease response. 
Each center must allocate the responsibility for the administration of the PRO instruments to a 
specific individual (e.g., a research nurse or study coordinator) and, if possible, assign a 
back-up person to cover if that individual is absent. The PRO questionnaires must be 
administered and completed on the days specified in the SoAs (Section 1.3). The EORTC 
QLQ-C30 should always be completed prior to the EORTC QLQ-LC13 module.
It is important that the site staff carefully explain the significance and relevance of the data to 
participants so that they are motivated to comply with data collection. The following best 
practice guidelines should be followed when collecting PRO data via ePRO:
!
It is preferred that PRO questionnaires are completed prior to any other study procedures 
(following informed consent) and before discussion of disease progression to avoid 
biasing the participant’s responses to the questions.
!
PRO questionnaires must be completed in private by the participant.
!
Participants should be given sufficient time to complete the PRO questionnaires at their 
own speed.
!
The research nurse or appointed site staff should stress that the information is 
confidential. Therefore, if the participant has any medical problems, he/she should discuss 
them with the doctor or research nurse separately from the ePRO assessment.

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!
The research nurse or appointed site staff must train the participant on how to use the 
ePRO device using the materials and training provided with the ePRO device. The 
research nurse or appointed site staff must remind participants that there are no right or 
wrong answers and avoid introducing bias by not clarifying items. The participant should 
not receive help from relatives, friends, or clinic staff to answer the PRO questionnaires. 
A key aspect of study success is to have high PRO compliance. Therefore, it is essential that 
sites follow the SoAs and make sure the ePRO device is charged and fully functional at all 
times in order to minimize missing data.
9
STATISTICAL CONSIDERATIONS
On 14 December 2021, AstraZeneca took the decision to terminate enrolment for this study 
due to the evolving benefit risk profile of AZD2811 that does not support further development 
for the first-line treatment of patients with extensive stage small-cell lung cancer. Patients 
already enrolled in the study were able to continue to receive study treatment. 
As a result of this decision, the originally intended statistical analyses will be streamlined with 
respect to efficacy data and the focus of the abbreviated CSR will be on reporting safety data 
in full. Full details of the analyses will be given in the SAP. Sections from CSP v8.0 are 
retained below for reference, with some modifications and additional high-level descriptions 
of changes as applicable.
9.1
Of note, no interim analyses, primary analysis or exploratory 
external controls analysis will be carried out and the study will 
proceed to final analysis, based upon which the abbreviated CSR 
will be written. As a result of the early termination, the DCO for the final 
analysis in this study is planned for 18 June 2022.Statistical Hypotheses
The study is single arm, so there will be no formal statistical hypotheses. The analysis for the 
study will be descriptive.
9.2
Sample Size Determination
As a result of the decision on 14 December 2021 to terminate enrolment for this study, no 
interim or primary analyses will be conducted and the study will proceed to final analysis, 
based upon which the CSR will be written. The DCO for the final analysis is planned for 18 
June 2022. Details of the originally intended sample size and planned analyses are retained 
below for reference. Note that as of CSP v8.0 the starting dose of AZD2811 in the 
maintenance phase was reduced to 
. Due to early termination of enrolment, CSPv8 was 
never implemented and no new pts started treatment with AZD2811; all new patients 
transitioning into the maintenance phase were treated with durvalumab monotherapy.
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Approximately 100 eligible participants will be assigned study treatment into the induction 
phase of the study. At the end of the induction phase, those participants who achieve CR, PR, 
or SD according to RECIST v1.1 will enter the maintenance phase. A minimum of 
80 evaluable participants is required for the maintenance phase. To achieve this, additional 
participants may need to be recruited into the induction phase. 
From CSP v8.0 onwards, the starting dose of AZD2811 in the maintenance phase was
, the study sought to achieve 80 evaluable participants on that starting dose.
The primary efficacy endpoint is a landmark analysis of the proportion of participants who are 
APF12 and who have not progressed during EP-durvalumab based induction therapy. The 
primary analysis will be triggered when a minimum of 80 evaluable participants have had the 
opportunity to be on the study for approximately 52 weeks + 1 week from the first dose of 
study therapy in the induction phase. The proportion APF12 and 95% CI will be summarized 
using the Kaplan-Meier estimate. Based on decision framework (Frewer et al, 2016) with a 
target value (Senovilla et al) of 
 and a lower reference value (LRV) of 
, the sample 
size will permit demonstration of exceeding a 
 landmark PFS at 12 months with 80% 
probability if the observed landmark PFS at 12 months is at least 
 at the primary 
analysis.
Two administrative interim analyses will be carried out as described in Section 9.5.
The DCO for the final CSR analysis will occur approximately 18 months following the last 
participant’s first dose, unless the study is terminated based on any of the reasons in 
Section 4.4.
Enrolled/screened
Estimated 185 participants
Assigned to study intervention 
Estimated 130 participants
Evaluable participants
Estimated 90 participants a
a
80 evaluable at 
 AZD2811 starting maintenance dose.
Note: “Enrolled” means a participant’s, or their legally acceptable representative’s, agreement 
to participate in a clinical study following completion of the informed consent process. 
Potential participants who are screened for the purpose of determining eligibility for the study, 
but are not assigned in the study, are considered “screen failures”, unless otherwise specified 
by the protocol. “Assigned” means that a participant has completed the screening period and 
has received at least one dose of study treatment. 
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9.3
Populations for Analyses
The originally planned study populations are defined in Table 23, however, from CSP v9.0 
onwards the three analysis sets pertaining to ‘Evaluable’ participants will not be defined for 
the abbreviated CSR as they are no longer required for efficacy analyses.
Table 23
Populations for Analysis
Population/Analysis set
Description
Enrolled/screened
All participants who sign the informed consent form
Assigned to study intervention
All participants assigned a study intervention
Evaluable
All participants who entered the maintenance phase and who received at 
least one dose/have been exposed to any AZD2811 + durvalumab
Evaluable for objective 
response induction phase
Dosed participants in the induction phase who had measurable disease at 
baseline
Evaluable for objective 
response maintenance phase
Dosed participants who entered the maintenance phase, received at least one 
dose of AZD2811 + durvalumab on Cycle 5 Day 1, and who had 
measurable disease at baseline
Pharmacokinetics
All participants who received at least one dose of AZD2811 + durvalumab 
with at least one reportable concentration
Biomarker
All participants who had a baseline biopsy assessment
Safety
All participants who received at least one dose/have been exposed to any
study intervention
9.4
Statistical Analyses
Analyses will be performed by Covance under the direction of Oncology Biometrics, 
AstraZeneca. The statistical analysis plan (SAP) will include a more technical and detailed 
description of the statistical analyses described in this section. Given the decision on 14 
December 2021 to terminate enrolment, the abbreviated CSR will focus on reporting of safety 
endpoints as there were were too few patients who received AZD2811 in combination with 
durvalumab (9 patients) to give meaningful efficacy analyses. Therefore, the efficacy analyses 
will be streamlined and this will be fully documented in the SAP. Any deviations from this 
plan will be reported in the CSR.
9.4.1
General Considerations
The main aims of the study are to assess the efficacy, safety, and tolerability of the study 
intervention in participants who entered the maintenance phase with ES-SCLC. 
All analyses will be descriptive, including summaries from Kaplan-Meier curves. Continuous 
variables will be summarized by the number of observations, mean, standard deviation, 
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data will include geometric mean, geometric standard deviation, and coefficient of variation 
(CV). Categorical variables will be summarized by frequency counts and percentages for each 
category. Unless otherwise stated, percentages will be calculated out of the population total 
for the relevant analysis.
The summaries, where applicable, will be presented by the following: All participants, 
participants who only entered the induction phase, and participants who entered the induction 
and maintenance phase, unless otherwise specified. 
From CSP v8.0 onwards, the starting dose of AZD2811 in the maintenance phase was 
intended to be 
, and the study would therefore report efficacy and safety by 
maintenance phase starting dose of AZD2811 as applicable. Due to early termination of 
enrolment, CSPv8 was never implemented and no new pts started treatment with AZD2811; 
all new patients transitioning into the maintenance phase were treated with durvalumab 
monotherapy. Further details will be provided in the SAP.
Baseline will be the last non-missing value obtained prior to the first dose/administration of 
study intervention in the induction phase, and any information taken after first 
dose/administration of study intervention in the induction phase is regarded as post-baseline 
information. All analyses will use this baseline unless otherwise specified.
An exploratory analysis using external control data will be conducted to compare AZD2811 + 
durvalumab to durvalumab from the CASPIAN study and will be reported outside of the CSR.
Induction Phase
The induction phase will be from the first dose of platinum-based induction therapy (cisplatin 
or carboplatin plus etoposide) + durvalumab until the first dose of AZD2811 + durvalumab in 
the maintenance phase.
Maintenance Phase
At the end of the induction phase, participants will be assessed for disease progression per 
RECIST v1.1. All participants who have not progressed will be treated with AZD2811 + 
durvalumab or durvalumab monotherapy as maintenance therapy until confirmed radiological 
PD, unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation 
criterion is met.
Follow-up Period
Period from participant’s last dose of any study intervention until end of study.
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Demographic data
Characteristics of the participants, including medical history and disease characteristics at 
baseline, will be listed for each participant and summarized where appropriate.
Exposure
Exposure to study intervention, ie, total amount of study drug received, will be listed for all 
participants.
Total treatment duration will be summarized by the following: Mean, standard deviation, 
minimum, maximum, median, and number of observations. In addition, the number and 
percentages of participants with at least one dose interruption and at least one dose reduction 
will be presented separately for the planned length of Cycle 1, defined as 
, and for any 
time following this initial phase of study. The number of cycles of each study drug will be 
summarized. Participants are counted as receiving a cycle of study drug as soon as any 
infusion has started in that cycle.
Dose intensity data will be summarized using medians and quartiles, as well as the minimum 
and maximum values.
9.4.2
Efficacy
From CSP v8.0 onwards, the starting dose of AZD2811 in the maintenance phase was
, the study will therefore primarily report efficacy for the 
 AZD2811 dose. 
Further sensitivity analyses will be defined in the SAP.
From CSP v9.0 onwards, study enrolment has been terminated and the study will proceed to 
final analysis and an abbreviated CSR. As a result of this, efficacy analyses will be 
streamlined as there were too few patients who received AZD2811 in combination with 
durvalumab (9 patients) to give meaningful analyses.
Sections below containing original plans for reporting efficacy are retained for reference but 
notable changes will include:
!
No summaries of efficacy data will be provided, with the exception of PK, and 
selected efficacy data will be listed only.
!
DoR, PFS2, PRO and breakthrough pain therapy endpoints will no longer be reported 
in the abbreviated CSR.
Full details of planned efficacy analyses will be documented in the SAP.
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9.4.2.1
Primary Endpoint(s)
The primary efficacy endpoint is landmark PFS APF12, where PFS is defined as the time 
from the first dose of study intervention in the induction phase until objective disease 
progression (as assessed by the investigator per RECIST v1.1) or death from any cause, 
whichever comes first. The primary endpoint will only be summarized for participants who 
entered the maintenance phase and received
AZD2811 + durvalumab on 
 
Day 1 and includes all data from the first dose of study intervention in the induction phase.
9.4.2.2
Secondary Endpoints
The secondary efficacy endpoints include landmark OS12, OS15, OS18, landmark PFS APF6 
and APF9, and OS, PFS, ORR, PK, and health-related QoL. Unless specified otherwise, the 
secondary endpoints will only be summarized for participants who receive
AZD2811 
+ durvalumab in the maintenance phase and include all data from first dose of study 
intervention in the induction phase. The ORR will be presented for all participants in the 
induction phase. The ORR will also be presented for all participants who received AZD2811 + 
durvalumab in the maintenance phase and include all data from first dose of study intervention 
in the induction phase.
9.4.2.3
Progression-free survival
The PFS analysis is for those participants who entered the maintenance phase and received 
AZD2811 + durvalumab on 
 Day 1.
Progression-free survival is defined as the time interval from the first dose of study 
intervention in the induction phase until the date of objective disease progression or death (by 
any cause, in the absence of progression) regardless of whether the participant withdraws from 
treatment or received another anticancer therapy prior to progression. Participants who have 
not progressed (defined as CR, PR, or SD by RECIST v1.1) at the time of analysis will be 
censored at the time of the last evaluable RECIST v1.1 assessment.
However, if the participant progresses or dies after 2 or more consecutively missed radiologic 
visits, the participant will be censored at the time of the last evaluable RECIST v1.1 
assessment prior to the 2 missed visits. Note: A NE visit is not considered as a missed visit. If 
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the participant is NE post-baseline RECIST v.1.1, they will be censored at Day 1 unless they 
die within 2 visits of baseline (in which case, their date of death will be used).
Progression-free survival will be derived based on scan/assessment dates, not the scheduled 
visit dates. If RECIST v1.1 assessments contributing toward a particular visit are performed 
on different dates, then the date of progression will be determined based on the earliest of the 
dates of the component that triggered the progression. With regard to censoring, a participant 
will be censored at the latest of the dates contributing to a particular overall visit assessment. 
Summaries (number of events, medians, proportion, and 95% CI for progression free at fixed 
time points using the Kaplan-Meier estimate) and Kaplan-Meier plots will be provided. A 2-
sided 95% CI of the median PFS will be produced in addition to the 25th and 75th percentiles. 
The fixed time points may include the following: 6 weeks, 12 weeks, 18 weeks, 24 weeks, 
36 weeks, 44 weeks, and 52 weeks. Other fixed time points may be included and will be 
documented in the SAP. 
The landmark of the proportion of participants APF6, APF9, and APF12 will be defined as the 
Kaplan-Meier estimate of PFS (per RECIST v1.1 as assessed using site investigator 
assessments) at 24 + 1 weeks, 36 + 1 weeks, and 52 + 1 weeks to align with the planned scan 
schedule and allowing for a 1-week window. Confidence intervals will also be presented.
Time from start of study therapy in the induction phase to second progression
The analysis of the exploratory endpoint PFS2 is for those participants who entered the 
maintenance phase.
The exploratory endpoint PFS2 will be defined as the time from the start of study therapy in 
the induction phase to the earliest of the progression event subsequent to that used for the PFS 
endpoint, or death. The date of PFS2 will be recorded by the investigator in the eCRF and 
defined according to local standard clinical practice, and may involve any of the following: 
Objective radiological imaging, symptomatic progression, or death. The site will be asked 
whether the participant has had a second progression event on a regular basis following the 
first progression event used for the primary variable PFS (the first progression) and the status 
is recorded. Participants alive and for whom a second disease progression has not been 
observed will be censored at the last time known to be alive and without a second disease 
progression, and is censored at the latest of the PFS or PFS2 assessment date if the participant 
has not had a second progression or has died.
Overall survival
The OS analysis is for those participants who entered the maintenance phase and received
 AZD2811 + durvalumab on 
 Day 1. For the participants who do not enter the 
maintenance phase, their survival data will only be listed.
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Overall survival is defined as the time from the date of first dose of study intervention in the 
induction phase until death due to any cause, regardless of whether the participant withdraws 
from study therapy or received another anticancer therapy. Any participant not known to have 
died at the time of analysis will be censored based on the last recorded date on which the 
participant was known to be alive.
Note: Survival calls will be made in the week following the date of DCO for the analysis and, 
if participants are confirmed to be alive or if the death date is after the DCO date, these 
participants will be censored at the date of DCO.
Summaries (number of events, medians, proportion, and 95% CI for participants alive at fixed 
time points using the Kaplan-Meier estimate) and Kaplan-Meier plots will be provided. A 2-
sided 95% CI of the median OS will be produced in addition to the 25th and 75th percentiles. 
The fixed time points may include the following: 6 months, 9 months, 12 months, 15 months, 
and 18 months. Other fixed time points may be included and will be documented in the SAP.
The landmark of the proportion of participants alive: OS12, OS15, and OS18, will be defined 
as the Kaplan-Meier estimate of OS at 12, 15, and 18 months, respectively. Confidence 
intervals will also be presented.
Tumor response
Tumor response data will be summarized for dosed participants with measurable disease at 
baseline, and separately for dosed participants with measurable or non-measurable disease at 
baseline.
Tumor response data will be listed using the following response categories: CR, PR, SD, 
Non-CR/Non-PD, PD, and NE.
Objective response rate is defined as the percentage of participants with confirmed objective 
response (CR or PR). It will be based on a subset of all treated participants with measurable 
disease at baseline, per the site investigator. A confirmed response of CR/PR means that a 
response of CR/PR is recorded at one visit and confirmed by repeat imaging not less than 4 
weeks after the visit when the response was first observed with no evidence of progression 
between the initial and CR/PR confirmation visit. Data obtained up until progression, or last 
evaluable assessment in the absence of progression, will be included in the assessment of 
ORR. Also, only data obtained before the start of subsequent anticancer treatment (excluding 
radiotherapy) will be included. Therefore, both visits contributing to a confirmed response 
must be prior to progression and prior to subsequent anticancer treatment.
Summaries will be produced that present the number and percentage of participants with a 
tumor response (CR/PR). The ORR will be presented with a 2-sided 95% CI using the 

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Clopper-Pearson (exact probability) method. Participants who have missing overall response 
assessments at all visits will be considered as non-responders, and will therefore be counted in 
the denominator of ORR. The ORR will be summarized for all participants in the induction 
phase and, in addition, ORR will be summarized for those participants who were in the 
maintenance phase.
Waterfall plots (bar plots) and spider plots (individual line plots of percent change from 
baseline over time), indicating the percentage change from baseline in sum of the diameters of 
the TLs, will be produced. Specifically, these plots will be based on the sum of diameters as 
entered in the database, including no adjustment as a function of tumor response in the case of 
participants with lymph node regression.
Duration of Response 
The DoR is defined as the time from the date of first documented response (which is 
subsequently confirmed) until date of first documented progression or death (by any cause, in 
the absence of disease progression). The end of response should coincide with the date of 
progression or death from any cause used for the PFS endpoint. The time of the initial 
response will be defined as the latest of the dates contributing toward the first visit that was 
PR or CR that was subsequently confirmed. 
The DoR will be analyzed in the same manner as PFS, if the number of participants with DoR 
allows. In addition, Swimmer plots will be produced.
If a participant does not progress following a response, then their DoR will use the PFS 
censoring date at the date at which that participant is censored for DoR.
9.4.3
Patient-reported outcomes
From CSP v9.0 onwards, study enrolment has been terminated and the study will proceed to 
an abbreviated CSR. As a result of this, efficacy analyses will be streamlined and PRO data 
will no longer be reported.
Patient-reported outcome questionnaires will be assessed using the EORTC QLQ-C30 with 
the QLQ-LC13 module (health-related QoL and lung cancer-specific symptoms). For PRO 
symptoms and health-related QoL endpoints, the main concepts of interest are based on the 
CASPIAN study. In the CASPIAN study, the main concepts of interest were identified using a 
literature review and detailed qualitative interviews with SCLC patients and clinicians. The 
key symptoms were: Cough, hemoptysis, dyspnea, chest pain, insomnia, fatigue, and appetite 
loss. Therefore, these key SCLC symptoms will be identified as primary measures of interest. 
In addition, physical functioning and overall health status domains of the EORTC QLQ-C30 
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Summary statistics for mean score, standard deviation, median, and range will be presented by 
visits until there are less than one third of participants with evaluable data. Box plots may also 
be presented.  
Time to symptom and function/health-related QoL deterioration will be analyzed for each of 
the symptom scales/items, function scales, and global health status/QoL in EORTC QLQ-C30 
and QLQ-LC13. This will be assessed using the same methods as for the primary analysis. 
For each of the symptom scales/items, functional scales, and global health status/QoL, time to 
deterioration will be presented using a Kaplan-Meier plot. Summaries of the number and 
percentage of participants experiencing a clinically relevant deterioration or death, and the 
median time to deterioration, will also be provided.
Further details on how these data will be analyzed will be detailed and prespecified in the 
SAP.
9.4.3.1
EORTC QLQ-C30
Summaries of original and change from baseline values of each symptom scale/item, the 
global health-related QoL score, and each functional domain will be reported by visit. 
Graphical presentations may also be produced as appropriate. Details will be provided in the 
SAP. 
9.4.3.2
EORTC QLQ-LC13
Summaries of original and change from baseline values of each symptom (dyspnea, cough, 
hemoptysis, chest pain, arm/shoulder pain, and other pain) and each treatment-related side 
effect (sore mouth, dysphagia, peripheral neuropathy, and alopecia) will be reported by visit. 
Graphical presentations may also be produced as appropriate. Details will be provided in the 
SAP.  
9.4.4
Safety
From CSP v9.0 onwards, study enrolment has been terminated and the study will proceed to 
an abbreviated CSR. The abbreviated CSR will present a full safety report and as such the 
analysis of safety endpoints will remain largely unchanged. Any changes to the planned 
analyses below will be fully described in the SAP and will be limited to instances where, in 
light of the early termination of enrolment, listings of specific data points are more appropriate 
than summaries.
Safety and tolerability will be assessed in terms of AEs (including SAEs), deaths, laboratory 
data, vital signs, ECGs, physical examination, and exposure. These will be collected for all 
participants. Data from all cycles of study intervention will be combined in the presentation of 
safety data, along with summaries of the induction phase and the maintenance phase unless 

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otherwise specified. Safety analyses will be performed using the safety analysis set. Safety 
data will be presented using descriptive statistics. Analyses will be presented for the overall 
study and separately for the induction and maintenance phases.
From CSP v8.0 onwards, the patients who were transitioned onto the maintenance phase 
received 
 of AZD2811, and the study will therefore report efficacy and safety by 
maintenance phase starting dose of AZD2811 as applicable. Further details will be provided in 
the SAP. In general, the baseline value for statistical analysis is the last non-missing value 
prior to administration of the first dose of study intervention in the induction phase. Details 
will be described in the SAP. 
Adverse Events
Adverse events will be coded using the most recent version of the Medical Dictionary for 
Regulatory Activities (MedDRA) that will have been released for application by 
AstraZeneca/designee. 
“On treatment” will be defined as assessments between date of start dose of study intervention 
in the induction phase and 90 days following discontinuation of study intervention (90 days 
after the last dose of AZD2811 + durvalumab or durvalumab + EP). For AEs, on treatment (or 
treatment-emergent AEs [TEAEs]), will be defined as any AEs that started after dosing or 
prior to dosing and which worsen following exposure to study intervention.  
Adverse events observed up until 90 days following discontinuation of study intervention (ie, 
90 days after the last dose of AZD2811 + durvalumab or durvalumab + EP) or until the 
initiation of the first subsequent therapy following discontinuation of study intervention 
(whichever occurs first) will be used for reporting of AE summary tables. This will more 
accurately depict AEs attributable to study treatment only because a number of AEs up to 
90 days following discontinuation of study intervention are likely to be attributable to 
subsequent therapy. However, to assess the longer term toxicity profile, AE summaries will 
also be produced containing AEs observed up until 90 days following discontinuation of study 
intervention (ie, without taking subsequent therapy into account).
Any events in this phase that occur after a participant has received further therapy for cancer 
(following discontinuation of study intervention) will be flagged in the data listings.
A separate data listing of AEs occurring more than 90 days after discontinuation of study 
intervention will be produced if required. These events will not be included in AE summaries.
Adverse events will be presented by MedDRA system organ class, MedDRA preferred term, 
and CTCAE grade, including the number and percentage of participants reporting at least one 
event, number of events, and exposure adjusted rates, where appropriate. 
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An overview of AEs will be presented for each phase, including the number and percentage of 
participants with any AE, AEs with outcome of death, SAEs, and AEs leading to 
discontinuation of study intervention. 
Separate AE tables will be provided, taking into consideration the relationship with study 
intervention assessed by the investigator, CTCAE grade,  seriousness, death, and events 
leading to discontinuation of study intervention, as well as other action taken related to study 
intervention. 
Dose-limiting toxicities will be displayed in the listing for the DLT-evaluable participant 
population.
Full details of AE analyses will be provided in the SAP. 
Treatment Emergent
The following events are considered treatment emergent:
!
Adverse events with an onset date on or after the first dose of study intervention
!
Worsening of pre-existing events on or after the first dose of study intervention
Clinical Laboratory Safety Assessments
Laboratory data for hematology and clinical chemistry will be summarized. The frequency of 
changes with respect to normal ranges between baseline and each post-treatment time point 
will be tabulated. Shifts from baseline to maximum value during treatment will be evaluated 
for urinalysis.
Vital Signs and Physical Examination
Vital sign parameters will be presented for each treatment group. Summary statistics for 
continuous variables cover number of participants, mean, standard deviation, minimum, 
quartile 1, median, quartile 3, and maximum. Frequency tables cover number and percentage 
of participants in the respective category.
The baseline value will be the latest result obtained prior to the start of study intervention in 
the induction phase.
For each scheduled post-baseline visit, descriptive statistics for all vital sign parameters will 
be presented for observed values and absolute change from baseline.
Changes in vital signs will be examined at each visit. Frequencies of clinically noteworthy 
values (defined in the SAP) occurring during the clinical study will be presented.

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Details of vital sign analyses will be provided in the SAP.
All individual physical examination and targeted physical examination data will be listed only.
ECG
For the change from baseline summaries for ECG, the baseline value will be the latest result 
obtained prior to the start of study intervention in the induction phase.
The QTcF will be derived during creation of the reporting database using the reported ECG 
values (respiratory rate [RR] and QT):
QTcF = QT/RR(1/3), where RR is in seconds
9.4.4.1
Other Safety Endpoint(s)
The ECOG PS will be listed.
The number of participants who stop break-through pain therapy during maintenance therapy 
will also be summarized.
9.4.5
Other Analyses 
The PK, pharmacodynamic, demographic, safety, and tumor response data collected in this 
study may also be combined with similar data from other studies and explored using 
population PK and/or population PK-pharmacodynamic methods. The results of such analyses 
will be reported separately from the main CSR.
9.4.6
 
 
 
9.4.7
Pharmacokinetic Analyses
For each analyte, whole blood or serum concentrations for each scheduled time point will be 
summarized by visit using appropriate descriptive statistics. Protocol scheduled times will be 
used to present the PK concentration summary tables and corresponding geometric mean 
concentration-time figures. Additional details for the handling of non-quantifiable 
concentrations will be included in the SAP.
!
The geometric mean (gmean, calculated as exp[μ], where μ is the mean of the data on a 
logarithmic scale)
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!
gmean ± geometric standard deviation (gmean + gstandard deviation and gmean –
gstandard deviation), which are calculated as exp(μ ± s)
!
CV, calculated as 100 sqrt (exp[s2]-1), where s is the standard deviation of the data on a 
log scale
!
gmean ± standard deviation (calculated as exp[μ ± s])
!
Arithmetic mean, calculated using untransformed data
!
Standard deviation, calculated using untransformed data
!
Minimum
!
Maximum
!
Number of observations
!
Number of participants below lower limit of quantification
9.5
Interim Analyses 
Two interim analyses were originally planned. However, due to the decision on 14 December 
2021 to terminate enrolment for this study these will no longer be carried out. Details of the 
originally planned interim analyses are retained below.
These are administrative interim analyses, which is an administrative review of the data to 
trigger additional development work for AZD2811; as such, no modifications will be made to 
the current study, and the study will continue as planned. The review will consist of safety and 
tolerability outputs, including SAEs, TEAEs, exposure, and the efficacy endpoints of APF6 
and APF9 for the first and second interim analysis, respectively, including other important 
efficacy endpoints. At the second interim analysis the landmark PFS APF12 will also be 
assessed, it is anticipated that approximately 50 participants will have had the opportunity to 
be on the study for at least 12 months from the first dose of study therapy in the induction 
phase at the timing of the second interim analysis.
The first administrative interim analysis will be based on landmark PFS APF6 in participants 
who have not progressed during EP-durvalumab based induction therapy. The analysis will be 
triggered when a minimum of 80 evaluable participants have received AZD2811 + 
durvalumab and have had the opportunity to be on the study for approximately 24 weeks + 
1 week from the start of induction. Based on decision framework (Frewer et al, 2016) with a 
TV (Senovilla et al, 2012) of
 and a LRV of
 the sample size will permit 
demonstration of exceeding a
 landmark PFS APF6 with 
 probability if the observed 
landmark PFS APF6 is at least 
 at this interim analysis. 
From CSP v8.0 onwards, the starting dose of AZD2811 in the maintenance phase will be 
, all the interim analyses of efficacy will focus on the 
 dose.
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The second administrative interim analysis will be based on landmark PFS APF9 in 
participants who have not progressed during EP-durvalumab based induction therapy. The 
analysis will be triggered when a minimum of 80 evaluable participants have received 
AZD2811 + durvalumab and have had the opportunity to be on the study for approximately 
36 weeks + 1 week from the start of induction. Based on decision framework (Frewer et al, 
2016) with a TV of 
 and a LRV of 
, the sample size will permit demonstration of 
exceeding a 
 landmark PFS APF9 with 
 probability if the observed landmark PFS 
APF9 is at least 
 at this interim analysis. At the second interim analysis, the landmark 
PFS APF12 will also be assessed, as it is anticipated that approximately 50 participants will 
have had the opportunity to be on the study for at least 12 months from the first dose of study 
therapy in the induction phase at the timing of the second interim analysis. Based on decision 
framework (Frewer et al, 2016) with a TV of 
 and a LRV of 
, the sample size will 
permit demonstration of exceeding a 
 landmark PFS APF12 with 
 probability if the 
observed landmark PFS APF12 is at least 
 at this interim analysis.
The SAP will describe the planned interim analyses in greater detail.
9.6
Data Monitoring Committee
A SRC will be used to assess the participants in the safety run-in part of the maintenance 
phase of the study. The SRC structure is detailed in Appendix A 5
10
SUPPORTING DOCUMENTATION AND OPERATIONAL
CONSIDERATIONS
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Appendix A
Regulatory, Ethical, and Study Oversight Considerations
A 1
Regulatory and Ethical Considerations
!
This study will be conducted in accordance with the protocol and with the following:
∀
Consensus ethical principles derived from international guidelines, including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences International Ethical Guidelines
∀
Applicable International Conference for Harmonisation (ICH) Good Clinical Practice 
(GCP) Guidelines
∀
Applicable laws and regulations
!
The protocol, protocol amendments, informed consent form (ICF), Investigator’s 
Brochure (IB), and other relevant documents (e.g., advertisements) must be submitted to 
an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) by the 
investigator, and reviewed and approved by the IRB/IEC before the study is initiated.
!
Any amendments to the protocol will require IRB/IEC and applicable Regulatory 
Authority approval before implementation of changes made to the study design, except 
for changes necessary to eliminate an immediate hazard to study participants.
!
AstraZeneca will be responsible for obtaining the required authorizations to conduct the 
study from the concerned Regulatory Authority. This responsibility may be delegated to a 
Contract Research Organization (CRO), but the accountability remains with AstraZeneca.
!
The investigator will be responsible for providing oversight of the conduct of the study at 
the site and adherence to requirements of Code of Federal Regulations number 21 (21 
CFR), ICH guidelines, the IRB/IEC, European Regulation 536/2014 for clinical studies 
(if applicable), European Medical Device Regulation (MDR) 2017/745 for clinical device 
research (if applicable), and all other applicable local regulations.
Regulatory Reporting Requirements for Serious Adverse Events
!
Prompt notification by the investigator to the Sponsor of a serious adverse event (SAE) is 
essential so that legal obligations and ethical responsibilities toward the safety of 
participants and the safety of a study intervention under clinical investigation are met.
!
The Sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study intervention under clinical 
investigation. The Sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, IRB/IEC, and investigators.

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!
For all studies except those utilizing medical devices, investigator safety reports must be 
prepared for suspected unexpected serious adverse reactions  according to local regulatory 
requirements and Sponsor policy, and forwarded to investigators as necessary.
∀
European MDR 2017/745 for clinical device research (if applicable), and all other 
applicable local regulations
!
An investigator who receives an investigator safety report describing a SAE or other 
specific safety information (e.g., summary or listing of SAEs) from the Sponsor will 
review and then file it along with the IB or other documents and will notify the IRB/IEC, 
if appropriate according to local requirements.
A 2
Financial Disclosure
Investigators and sub-investigators will provide the Sponsor with sufficient, accurate financial 
information as requested to allow the Sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the course of the study 
and for one year after completion of the study.
A 3
Informed Consent Process
!
The investigator or his/her representative will explain the nature of the study to the 
participant or his/her legally authorized representative and answer all questions regarding 
the study.
!
Participants must be informed that their participation is voluntary, and they are free to 
refuse to participate and may withdraw their consent at any time and for any reason 
during the study. Participants or their legally authorized representative, defined as “an 
individual or judicial or other body authorized under applicable law to consent, on behalf 
of a prospective subject, to the subject’s participation in the clinical trial”, per ICH GCP 
E6(R2), 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 requirements, where applicable, and the IRB/IEC or 
study center.
!
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 authorized 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 the participant’s legally 
authorized representative.

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A participant who is rescreened is not required to sign another ICF if the rescreening occurs 
within 28 days from the previous ICF signature date. A participant who is re-treated following 
relapse will need to be re-consented.
The ICF will contain a separate section that addresses and documents the collection and use of 
any mandatory and/or optional human biological samples. The investigator or authorized 
designee will explain to each participant the objectives of the analysis to be done on the 
samples and any potential future use. Participants will be told that they are free to refuse to 
participate in any optional samples or the future use and may withdraw their consent at any
time and for any reason during the retention period. 
A 4
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 must be informed that his/her personal study-related data will be used by 
the Sponsor in accordance with local data protection law. The level of disclosure and use 
of their data must also be explained to the participant in the informed consent. 
!
The participant must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
Sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory authorities.
A 5
Committees Structure
A Safety Review Committee (SRC) will review the data from the safety run-in of the 
maintenance phase. 
The SRC will consist of:
!
Study Physician, who will chair the committee, or delegate
!
Principal Investigator or delegate from the investigational sites
In addition, one other physician from the following may be invited:
!
Sponsor Global Safety Physician or Medical Science Director

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The study clinical pharmacologist, study statistician, patient safety scientist, clinical project 
manager, and other experts may also be invited as appropriate. Further internal or external 
experts may be consulted by the SRC as necessary. The global safety physician or delegate 
should always be present at the SRC.
See the Safety Review Committee Charter for further details. 
A 6
Dissemination of Clinical Study Data
A description of this clinical study will be available on http://www.clinicaltrials.gov as will 
the summary of the study results when they are available. The clinical study and/or summary 
of study results may also be available on other websites according to the regulations of the 
countries in which the study is conducted.
A 7
Data Quality Assurance
!
All participant data relating to the study will be recorded on the electronic Case Report 
Form (eCRF) unless transmitted to the Sponsor or designee electronically (e.g., laboratory 
data). The investigator is responsible for verifying that data entries are accurate and 
correct by electronically signing the eCRF.
!
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF.
!
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections, and provide direct access to source data documents.
!
Monitoring details describing strategy (e.g., risk-based initiatives in operations and 
quality such as Risk Management and Mitigation Strategies and Analytical Risk-Based 
Monitoring), methods, responsibilities and requirements, including handling of 
non-compliance 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.
!
The Sponsor assumes accountability for actions delegated to other individuals (e.g., 
CROs).
!
Study monitors will perform ongoing source data verification to confirm that data entered 
into the eCRF by authorized site personnel are accurate, complete, and verifiable from 
source documents; that the safety and rights of participants are being protected; and that 
the study is being conducted in accordance with the currently approved protocol and any 
other study agreements, ICH and GCP, and all applicable regulatory requirements.
!
Records and documents, including signed ICFs, pertaining to the conduct of this study 
must be retained by the investigator for 15 years after study completion or discontinuation 

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of the trial; or at least 2 years after local market approval for the indication for which it is 
being investigated; or, if no market approval is filed or is not approved for such 
indication, at least 2 years after the investigation is discontinued with local authorities; or 
per local regulations or institutional policies, whichever retention period is longer. 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.
A 8
Source Documents
!
Source documents provide evidence for the existence of the participant and substantiate 
the integrity of the data collected. Source documents are filed at the investigator’s site.
!
Data 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.
!
Definition of what constitutes source data can be found in the Clinical Study Agreement.
A 9
Study and Site Start and Closure
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 activated and will be the study start date.
The Sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the Sponsor or investigator may include, but 
are not limited to:
!
Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the Sponsor’s procedures, or GCP guidelines
!
Inadequate recruitment of participants by the investigator
!
Discontinuation of further study intervention development

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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(s) and should assure 
appropriate participant therapy and/or follow-up.
Participants from terminated sites will have the opportunity to be transferred to another site to 
continue the study.
A 10
Publication Policy
!
The results of this study may be published or presented at scientific meetings. If this is 
foreseen, the investigator agrees to submit all manuscripts or abstracts to the Sponsor 
before submission. This allows the Sponsor to protect proprietary information and to 
provide comments.
!
The Sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the Sponsor will generally support 
publication of multicenter studies only in their entirety and not as individual site data. In 
this case, a co-ordinating investigator will be designated by mutual agreement.
!
Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements.

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Appendix B
Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
B 1
Definition of Adverse Events
An adverse event (AE) is the development of any untoward medical occurrence in a patient or 
clinical study participant administered a medicinal product and which does not necessarily 
have a causal relationship with this treatment. An AE can therefore be any unfavorable and 
unintended sign (e.g., an abnormal laboratory finding), symptom (e.g., nausea, chest pain), or 
disease temporarily associated with the use of a medicinal product, whether or not considered 
related to the medicinal product. 
The term AE is used to include both serious and nonserious AEs and can include a 
deterioration of a pre-existing medical occurrence. An AE may occur at any time, including 
run-in or washout periods, even if no study intervention has been administered.
B 2
Definition of Serious Adverse Events
A serious adverse event (SAE) is an AE occurring during any study phase (ie, run-in, 
treatment, washout, follow-up), that fulfills one or more of the following criteria:
!
Results in death
!
Is immediately life-threatening
!
Requires in-participant hospitalization or prolongation of existing hospitalization 
!
Results in persistent or significant disability or incapacity 
!
Is a congenital anomaly or birth defect
!
Is an important medical event that may jeopardize the participant or may require medical 
treatment to prevent one of the outcomes listed above
The above instruction applies only when the malignant tumor event in question is a new 
malignant tumor (ie, it is not the tumor for which entry into the study is a criterion and that is 
being treated by the investigational product under study, and is not the development of new or 
progression of existing metastasis to the tumor under study). Malignant tumors that – as part 
of normal, if rare, progression – undergo transformation (eg, Richter’s transformation of 
B-cell chronic lymphocytic leukemia into diffuse large B-cell lymphoma) should not be 
considered a new malignant tumor.
Life-threatening
‘Life-threatening’ means that the participant was at immediate risk of death from the AE as it 
occurred, or it is suspected that use or continued use of the product would result in the 

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participant’s death. ‘Life-threatening’ does not mean that had an AE occurred in a more severe 
form it might have caused death (e.g., hepatitis that resolved without hepatic failure).
Hospitalization
Outpatient treatment in an emergency room is not in itself an SAE, although the reasons for it 
may be (e.g., bronchospasm, laryngeal edema). Hospital admissions and/or surgical operations 
planned before or during a study are not considered AEs if the illness or disease existed before 
the participant was enrolled in the study, provided that it did not deteriorate in an unexpected 
way during the study.
Important Medical Event or Medical Treatment
Medical and scientific judgment should be exercised in deciding whether a case is serious in 
situations where important medical events may not be immediately life-threatening or result in 
death, hospitalization, disability, or incapacity but may jeopardize the participant or may 
require medical treatment to prevent one or more outcomes listed in the definition of serious. 
These should usually be considered as serious.
Simply stopping the suspect drug does not mean that it is an important medical event; medical 
judgment must be used.
!
Angioedema not severe enough to require intubation but requiring intravenous 
hydrocortisone treatment
!
Hepatotoxicity caused by paracetamol (acetaminophen) overdose requiring treatment with 
N-acetylcysteine
!
Intensive treatment in an emergency room or at home for allergic bronchospasm
!
Blood dyscrasias (e.g., neutropenia or anemia requiring blood transfusion, etc) or 
convulsions that do not result in hospitalization
!
Development of drug dependency or drug abuse
Intensity Rating Scale:
!
Mild (awareness of sign or symptom, but easily tolerated)
!
Moderate (discomfort sufficient to cause interference with normal activities)
!
Severe (incapacitating, with inability to perform normal activities)
It is important to distinguish between serious and severe AEs. Severity is a measure of 
intensity, whereas seriousness is defined by the criteria in Appendix B 2. An AE of severe 
intensity need not necessarily be considered serious. For example, nausea that persists for 
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shown in Appendix B 2. On the other hand, a stroke that results in only a limited degree of 
disability may be considered a mild stroke but would be a SAE when it satisfies the criteria 
shown in Appendix B 2.
The grading scales found in the revised National Cancer Institute Common Terminology 
Criteria for Adverse Events (CTCAE) latest version will be utilized for all events with an 
assigned CTCAE grading. For those events without assigned CTCAE grades, the 
recommendation in the CTCAE criteria that converts mild, moderate, and severe events into 
CTCAE grades should be used. A copy of the CTCAE can be downloaded from the Cancer 
Therapy Evaluation Program website (http://ctep.cancer.gov). The applicable version of 
CTCAE should be described clearly.
B 3
A Guide to Interpreting the Causality Question
When making an assessment of causality, consider the following factors when deciding if 
there is a ‘reasonable possibility’ that an AE may have been caused by the drug.
!
Time Course. Exposure to suspect drug. Has the participant actually received the suspect 
drug? Did the AE occur in a reasonable temporal relationship to the administration of the 
suspect drug?
!
Consistency with known drug profile. Was the AE consistent with the previous 
knowledge of the suspect drug (pharmacology and toxicology) or drugs of the same 
pharmacological class? Or could the AE be anticipated from its pharmacological 
properties?
!
De-challenge experience. Did the AE resolve or improve on stopping or reducing the dose 
of the suspect drug?
!
No alternative cause. The AE cannot be reasonably explained by another etiology such as 
the underlying disease, other drugs, other host, or environmental factors.
!
Re-challenge experience. Did the AE reoccur if the suspected drug was reintroduced after 
having been stopped? AstraZeneca would not normally recommend or support a 
re-challenge.
!
Laboratory tests. A specific laboratory investigation (if performed) has confirmed the 
relationship.
In difficult cases, other factors could be considered, such as:
!
Is this a recognized feature of overdose of the drug?
!
Is there a known mechanism?

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Causality of ‘related’ is made if, following a review of the relevant data, there is evidence for 
a ‘reasonable possibility’ of a causal relationship for the individual case. The expression 
‘reasonable possibility’ of a causal relationship is meant to convey, in general, that there are 
facts (evidence) or arguments to suggest a causal relationship.
The causality assessment is performed based on the available data, including enough 
information to make an informed judgment. With no available facts or arguments to suggest a 
causal relationship, the event(s) will be assessed as ‘not related’.
Causal relationship in cases where the disease under study has deteriorated due to lack of 
effect should be classified as no reasonable possibility.
B 4
Medication Error
For the purposes of this clinical study, a medication error is an unintended failure or mistake 
in the treatment process for an AstraZeneca study intervention that either causes harm to the 
participant or has the potential to cause harm to the participant. 
A medication error is not lack of efficacy of the drug, but rather a human or process related 
failure while the drug is in control of the study site staff or participant.
Medication error includes situations where an error. 
!
Occurred
!
Was identified and intercepted before the participant received the drug
!
Did not occur, but circumstances were recognized that could have led to an error
Examples of events to be reported in clinical studies as medication errors:
!
Drug name confusion
!
Dispensing error, e.g., medication prepared incorrectly, even if it was not actually given 
to the participant
!
Drug not administered as indicated, e.g., wrong route or wrong site of administration
!
Drug not taken as indicated, e.g., tablet dissolved in water when it should be taken as a 
solid tablet 
!
Drug not stored as instructed, e.g., kept in the refrigerator when it should be at room 
temperature 
!
Wrong participant received the medication (excluding Interactive Response Technology 
[IRT]/Randomization and Trial Supply Management [RTSM] errors)
!
Wrong drug administered to participant (excluding IRT/RTSM errors)

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Examples of events that do not require reporting as medication errors in clinical studies:
!
Errors related to or resulting from IRT/RTSM - including those that lead to one of the 
above listed events that would otherwise have been a medication error 
!
Participant accidentally missed drug dose(s), e.g., forgot to take medication
!
Accidental overdose (will be captured as an overdose)
!
Participant failed to return unused medication or empty packaging
!
Errors related to background and rescue medication, or standard of care medication in 
open-label studies, even if an AstraZeneca product 
Medication errors are not regarded as AEs, but AEs may occur as a consequence of the 
medication error.

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Appendix C
Handling of Human Biological Samples
C 1
Chain of Custody
A full chain of custody is maintained for all samples throughout their lifecycle.
The investigator at each center keeps full traceability of collected biological samples from the 
participants while in storage at the center until shipment or disposal (where appropriate) and 
records relevant processing information related to the samples while at site.
The sample receiver keeps full traceability of the samples while in storage and during use until 
used or disposed of or until further shipment and keeps record of receipt of arrival and onward 
shipment or disposal.
AstraZeneca or delegated representatives will keep oversight of the entire lifecycle through 
internal procedures, monitoring of study sites, auditing or process checks, and contractual 
requirements of external laboratory providers.
Samples retained for further use will be stored in the AstraZeneca-assigned biobanks or other 
sample archive facilities and will be tracked by the appropriate AstraZeneca Team during the 
remainder of the sample lifecycle.
C 2
Withdrawal of Informed Consent for Donated Biological Samples 
AstraZeneca ensures that biological samples are returned to the source or destroyed at the end 
of a specified period, as described in the informed consent.
If a participant withdraws consent to the use of donated biological samples, the samples will 
be disposed of/destroyed/repatriated, and the action documented. If samples are already 
analyzed, AstraZeneca is not obliged to destroy the results of this research.
Following withdrawal of consent for biological samples, further study participation should be 
considered in relation to the withdrawal processes outlined in the informed consent.
The investigator:
!
Ensures participant’s withdrawal of informed consent to the use of donated samples is 
highlighted immediately to AstraZeneca or delegate.
!
Ensures that relevant human biological samples from that participant, if stored at the 
study site, are immediately identified, disposed of as appropriate, and the action 
documented.
!
Ensures that the participant and AstraZeneca are informed about the sample disposal.

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AstraZeneca ensures the organization(s) holding the samples is/are informed about the 
withdrawn consent immediately and that samples are disposed of or repatriated as appropriate, 
and the action is documented and study site is notified.
C 3
International Airline Transportation Association 6.2 Guidance 
Document
LABELING AND SHIPMENT OF BIOHAZARD SAMPLES
International Airline Transportation Association (IATA) 
(https://www.iata.org/whatwedo/cargo/dgr/Pages/download.aspx) classifies infectious 
substances into 3 categories: Category A, Category B, or Exempt.
Category A Infectious Substances are infectious substances in a form that, when exposure to 
it occurs, is capable of causing permanent disability, is life-threatening, or causes a fatal 
disease in otherwise healthy humans or animals. 
Category A Pathogens are, eg, Ebola, Lassa fever virus. Infectious substances meeting these 
criteria, which cause disease in humans or both in humans and animals, must be assigned to 
UN 2814. Infectious substances, which cause disease only in animals, must be assigned to 
UN 2900.
Category B Infectious Substances are infectious Substances that do not meet the criteria for 
inclusion in Category A. Category B pathogens are, eg, Hepatitis A, C, D, and E viruses. They 
are assigned the following UN number and proper shipping name:
!
UN 3373 – Biological Substance, Category B
!
Are to be packed in accordance with UN 3373 and IATA 650
Exempt - Substances that do not contain infectious substances or substances that are unlikely 
to cause disease in humans or animals are not subject to these Regulations unless they meet 
the criteria for inclusion in another class.
!
Clinical study samples will fall into Category B or exempt under IATA regulations
!
Clinical study samples will routinely be packed and transported at ambient temperature in 
IATA 650 compliant packaging 
(https://www.iata.org/whatwedo/cargo/dgr/Documents/DGR-60-EN-PI650.pdf)
!
Biological samples transported in dry ice require additional dangerous goods specification 
for the dry-ice content

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Appendix D
D 1
D 2
CCI
CCI
CCI
CCI
CCI
CCI

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CCI

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CCI

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Appendix E
Actions Required in Cases of Increases in Liver Biochemistry 
and Evaluation of Hy’s Law
E 1
Introduction
This Appendix describes the process to be followed in order to identify and appropriately 
report Potential Hy’s Law (PHL) cases and Hy’s Law (Veuillen et al, 2012) cases. It is not 
intended to be a comprehensive guide to the management of elevated liver biochemistries. 
During the course of the study, the investigator will remain vigilant for increases in liver 
biochemistry. The investigator is responsible for determining whether a participant meets 
potential PHL criteria at any point during the study.
All sources of laboratory data are appropriate for the determination of PHL and HL events; 
this includes samples taken at scheduled study visits and other visits, including all local 
laboratory evaluations even if collected outside of the study visits; for example, PHL criteria 
could be met by an elevated alanine aminotransferase ALT and/or elevated total bilirubin 
(TBL) from a local laboratory. 
The investigator will also review adverse event (AE) data (e.g., for AEs that may indicate 
elevations in liver biochemistry) for possible PHL events.
The investigator participates, together with AstraZeneca clinical project representatives, in 
review and assessment of cases meeting PHL criteria to agree whether HL (Veuillen et al, 
2012) criteria are met. Hy’s Law criteria are met if there is no alternative explanation for the 
elevations in liver biochemistry other than Drug Induced Liver Injury (DILI) caused by the 
investigational product (IP). 
The investigator is responsible for recording data pertaining to PHL/HL cases and for 
reporting serious adverse events (SAEs) and AEs according to the outcome of the review and 
assessment in line with standard safety reporting processes.
E 2
Definitions
Potential Hy’s Law
Aspartate aminotransferase (AST) or ALT  ≥3 × ULN together with TBL ≥2× ULN at any 
point during the study following the start of study medication irrespective of an increase in 
alkaline phosphatase (ALP).

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Hy’s Law
Aspartate aminotransferase or ALT ≥3× ULN together with TBL ≥2× ULN, where no other 
reason, other than the IP, can be found to explain the combination of increases, e.g., elevated 
ALP indicating cholestasis, viral hepatitis, or another drug. 
For PHL and HL, the elevation in transaminases must precede or be coincident with (ie, on the 
same day) the elevation in TBL, but there is no specified time frame within which the 
elevations in transaminases and TBL must occur.
E 3
Identification of Potential Hy’s Law Cases
In order to identify cases of PHL, it is important to perform a comprehensive review of 
laboratory data for any participant who meets any of the following identification criteria in 
isolation or in combination:
!
ALT ≥3 × ULN
!
AST ≥3 × ULN
!
TBL ≥2 × ULN
Local Laboratories Being Used:
The investigator will, without delay, review each new laboratory report and if the 
identification criteria are met, will:
!
Notify the AstraZeneca representative 
!
Determine whether the participant meets PHL criteria (see Section E 2 for definition) by 
reviewing laboratory reports from all previous visits
!
Promptly enter the laboratory data into the laboratory eCRF
E 4
Follow-up
E 4.1
Potential Hy’s Law Criteria not met
If the participant does not meet PHL criteria the investigator will:
!
Inform the AstraZeneca representative that the participant has not met PHL criteria.
!
Perform follow-up on subsequent laboratory results according to the guidance provided in 
the Clinical Study Protocol.

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E 4.2
Potential Hy’s Law Criteria met
If the participant does meet PHL criteria, the investigator will:
!
Notify the AstraZeneca representative who will then inform the central Study Team 
!
Within one day of PHL criteria being met, the investigator will report the case as an SAE 
of Potential Hy’s Law; serious criteria ‘Important medical event’ and causality 
assessment ‘yes/related’ according to CSP process for SAE reporting
!
For participants who met PHL criteria prior to starting IP, the investigator is not required 
to submit a PHL SAE unless there is a significant change# in the participant’s condition
!
The Study Physician contacts the investigator to provide guidance, discuss and agree an 
approach for the study participants’ follow-up (including any further laboratory testing), 
and ensure the continuous review of data
!
Subsequent to this contact, the investigator will:
∀
Monitor the participant until liver biochemistry parameters and appropriate clinical 
symptoms and signs return to normal or baseline levels, or as long as medically 
indicated. Completes follow-up SAE Form as required.
∀
Investigate the etiology of the event and perform diagnostic investigations as 
discussed with the Study Physician. 
∀
Complete the 3 Liver eCRF modules as information becomes available 
#A ‘significant’ change in the participant’s condition refers to a clinically relevant 
change in any of the individual liver biochemistry parameters (ALT, AST, or TBL) in 
isolation or in combination, or a clinically relevant change in associated symptoms. The 
determination of whether there has been a significant change will be at the discretion of the 
investigator; this may be in consultation with the Study Physician if there is any uncertainty.
E 5
Review and Assessment of Potential Hy’s Law Cases
The instructions in this section should be followed for all cases where PHL criteria are met.
As soon as possible after the biochemistry abnormality was initially detected, the Study 
Physician contacts the investigator in order to review available data and agree on whether 
there is an alternative explanation for meeting PHL criteria other than DILI caused by the IP, 
to ensure timely analysis and reporting to health authorities within 15 calendar days from date 
PHL criteria was met. The AstraZeneca Global Clinical Lead or equivalent and Global Safety 
Physician will also be involved in this review, together with other subject matter experts as 
appropriate. 

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According to the outcome of the review and assessment, the investigator will follow the 
instructions below.
Where there is an agreed alternative explanation for the ALT or AST and TBL elevations, 
a determination of whether the alternative explanation is an AE will be made and, 
subsequently, whether the AE meets the criteria for a SAE:
!
If the alternative explanation is not an AE, record the alternative explanation on the 
appropriate eCRF
!
If the alternative explanation is an AE/SAE: Update the previously submitted Potential 
Hy’s Law SAE and AE eCRFs accordingly with the new information (reassessing event 
term; causality and seriousness criteria) following the AstraZeneca standard processes.
If it is agreed that there is no explanation that would explain the ALT or AST and TBL 
elevations other than the IP:
!
Send updated SAE (report term ‘Hy’s Law’) according to AstraZeneca standard 
processes. 
∀
The ‘Medically Important’ serious criterion should be used if no other serious 
criteria apply
∀
As there is no alternative explanation for the HL case, a causality assessment of 
‘related’ should be assigned
If there is an unavoidable delay of over 15 calendar days in obtaining the information 
necessary to assess whether or not the case meets the criteria for HL, then it is assumed that 
there is no alternative explanation until such time as an informed decision can be made:
!
Provide any further update to the previously submitted SAE of Potential Hy’s Law, 
(report term now ‘Hy’s Law case’) ensuring causality assessment is related to IP and 
seriousness criteria is medically important, according to CSP process for SAE reporting.
!
Continue follow-up and review according to agreed plan. Once the necessary 
supplementary information is obtained, repeat the review and assessment to determine 
whether HL criteria are still met. Update the previously submitted PHL SAE report 
following CSP process for SAE reporting according to the outcome of the review, and 
amend the reported term if an alternative explanation for the liver biochemistry elevations 
is determined.
E 6
Actions Required When Potential Hy’s Law Criteria are Met 
Before and After Starting Study Intervention 

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This section is applicable to participants with liver metastases who meet PHL criteria on study 
intervention, having previously met PHL criteria at a study visit prior to starting study 
intervention.
At the first on-study intervention occurrence of PHL criteria being met, the investigator will 
determine if there has been a significant change in the participants’ condition# compared with 
the last visit where PHL criteria were met#
!
If there is no significant change, no action is required
!
If there is a significant change, notify the AstraZeneca representative, who will inform the 
central Study Team, then follow the subsequent process described in Section E 4.2  
E 7
Actions Required for Repeat Episodes of Potential Hy’s Law
This section is applicable when a participant meets PHL criteria on study intervention and has 
already met PHL criteria at a previous on-study intervention visit.
The requirement to conduct follow-up, review, and assessment of a repeat occurrence(s) of 
PHL is based on the nature of the alternative cause identified for the previous occurrence. 
The investigator should determine the cause for the previous occurrence of PHL criteria being 
met and answer the following question:
Was the alternative cause for the previous occurrence of PHL criteria being met found 
to be the disease under study, e.g., chronic or progressing malignant disease, severe 
infection or liver disease, or did the participant meet PHL criteria prior to starting 
study intervention and at their first on-study intervention visit as described in Section 
E 6
If No: Follow the process described in Section E 4.2 for reporting PHL as an SAE
If Yes: Determine if there has been a significant change in the participant’s condition#
compared with when PHL criteria were previously met
!
If there is no significant change, no action is required
!
If there is a significant change#, follow the process described in Section E 4.2 for 
reporting PHL as an SAE
# A ‘significant’ change in the participant’s condition refers to a clinically relevant change in 
any of the individual liver biochemistry parameters (ALT, AST, or TBL) in isolation or in 
combination, or a clinically relevant change in associated symptoms. The determination of 

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whether there has been a significant change will be at the discretion of the investigator; this 
may be in consultation with the Study Physician if there is any uncertainty.
E 8
Recommended Laboratory Tests
Additional standard chemistry and coagulation tests
Gamma GT (GGT)
Lactate dehydrogenase (LDH)
Prothrombin time
International Ratio (INR)
Viral hepatitis
IgM anti-Hepatitis A Virus  
Hepatitis B surface antigen 
Immunoglobulin M (IgM) and Immunoglobulin G 
(IgG) hepatitis B core antigen (anti-HBc)
Hepatitis B Virus DNA a
IgG anti-Hepatitis C Virus (HCV)
HCV RNA b
IgM anti-Hepatitis E Virus (HEV)
HEV RNA
Other viral infections
IgM and IgG anti-Cytomegalovirus (CMV)
IgM and IgG anti-Herpes Simplex Virus
IgM and IgG anti-Epstein Barr Virus
Alcoholic hepatitis
Carbohydrate deficient transferrin (CD-transferrin) c
Autoimmune hepatitis
Antinuclear antibody (ANA)
Anti-liver/kidney microsomal Ab (anti-LKM)
Anti-smooth muscle Ab (ASMA)
Metabolic diseases
alpha-1-antitrypsin
Ceruloplasmin
Iron
Ferritin
Transferrin c
Transferrin saturation
a
HBV DNA is only recommended when IgG anti-HBc is positive
b
HCV RNA is only recommended when IgG anti-HCV is positive or inconclusive 
c
CD-transferrin and Transferrin are not available in China. Study teams should amend this list accordingly
E 9
References
Aithal et al, 2011
Aithal GP, Watkins PB, Andrade RJ, Larrey D, Molokhia M, Takikawa H, et al. Clinical 
Pharmacology and Therapeutics 2011;89(Research Report NN210296):806-15.

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FDA Guidance for Industry, July 2009
FDA Guidance for Industry (issued July 2009) ‘Drug-induced liver injury: Premarketing 
clinical evaluation’. Available from; https://www.fda.gov/regulatory-information/search-fda-
guidance-documents/drug-induced-liver-injury-premarketing-clinical-evaluation

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Appendix F
Guidelines for Evaluation of Objective Tumor Response 
Using RECIST v1.1 Criteria (Response Evaluation Criteria in 
Solid Tumors)
F 1
Introduction
This Appendix details the implementation of Response Evaluation Criteria in Solid Tumors 
(RECIST) v1.1 guidelines (Eisenhauer et al 2009) for this study with regard to investigator 
assessment of tumor burden, including protocol-specific requirements for this study. 
Additional special guidance is provided for determination of confirmation of radiological 
progression.
F 2
Definition of Measurable, Non-measurable, Target, and Non-
target Lesions
Measurable:
A lesion, which can be accurately measured at baseline as ≥10 mm in the longest diameter 
(except lymph nodes, which must have short axis1 diameter of ≥15 mm) with computed 
tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate 
repeated measurements.
Non-measurable:
!
All other lesions, including small lesions (longest diameter < 10 mm or pathological 
lymph nodes with ≥10 mm to < 15 mm short axis diameter at baseline2). 
!
Truly non-measurable lesions include the following: Bone lesions, leptomeningeal 
disease, ascites, pleural/pericardial effusion, inflammatory breast disease, lymphangitic 
involvement of skin or lung, and abdominal masses/abdominal organomegaly identified 
by physical examination (manual palpation) that is not measurable by CT or MRI.
!
Previously irradiated lesions3
!
Brain metastasis
                                               
1 The short axis is defined as the longest axis perpendicular to the long axis of the tumor.
2 Nodes with <10 mm short axis are considered non-pathological and should not be recorded or followed as 
non-target lesions (NTLs).
3 Localized post-radiation changes that affect lesion sizes may occur. Therefore, lesions that have been previously 
irradiated will not be considered measurable and must be selected as NTL at baseline and followed up as part of 
the NTL assessment.

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!
Skin lesions assessed by clinical examination
Special Cases:
!
Lytic bone lesions or mixed lytic–blastic lesions, with identifiable soft tissue components, 
can be considered measurable if the soft tissue component meets the definition of 
measurability. Blastic lesions are considered non-measurable.
!
Cystic metastases can be considered measurable lesions if they meet the criteria for 
measurability from a radiological point of view, but if non-cystic lesions are present in the 
same patient, these should be selected over cystic lesions as target lesions (TLs).
Target Lesions:
A maximum of 5 measurable lesions (with a maximum of 2 lesions per organ), representative 
of all lesions involved suitable for accurate repeated measurement, should be identified as TLs 
at baseline. Lymph nodes, in any location (local/regional and distant), are collectively 
considered as a single organ, with a maximum of 2 lymph nodes as TLs. A bilateral organ 
(e.g., adrenal glands), a segmented organ (e.g., liver), or multilobed organ (e.g., lung) is each 
considered as a single organ.
Non-Target Lesions:
Additional measurable lesions not recorded as TLs and non-measurable lesions (or sites of 
disease) should be identified as non-target lesions (NTLs) at baseline.
F 3
Imaging Modalities
The same method of assessment on the same imaging technique should be used to 
characterize each identified and recorded lesion at baseline and during follow-up visits.
A summary of the methods of assessment (imaging modalities) to be used for RECIST v1.1 
assessment of TLs, NTLs, and new lesions, is provided in Table 24.

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Table 24
Summary of Methods of Assessment
Target Lesions 
Non-Target Lesions
New Lesions
CT (preferred)
CT (preferred)
CT (preferred)
MRI
MRI
MRI
Plain X-ray
Plain X-ray, Chest X-ray
Chest X-ray
Bone scan
Clinical examination 
FDG-PET/CT
Clinical examination
Ultrasound
CT = Computed tomography; FDG-PET/CT = 18F-Fluorodeoxyglucose positron emission tomography/CT; 
MRI = Magnetic resonance imaging.
F 3.1
CT and MRI 
Computed tomography and MRI, each preferably with intravenous (IV) contrast, are generally 
considered to generate the best currently available and reproducible images for measurement 
of TL, assessment of NTL, and identification of any new lesions. 
It is recommended that IV contrast-enhanced CT examinations of the chest and abdomen 
(including the entire liver and both adrenal glands) will be used to assess tumor burden at 
baseline and follow-up visits. Any other areas of disease involvement (eg, pelvis, brain) 
should be additionally imaged based on the signs and symptoms of individual patients. In 
patients who are sensitive to IV CT contrast, a non-contrast CT examination of the chest and 
an MRI with IV MRI contrast of the abdomen is appropriate. In patients with severely 
compromised renal function, a non-contrast CT examination of the chest and abdomen is 
appropriate. For brain lesion assessment, MRI with IV contrast is the preferred method over 
IV contrast-enhanced CT. It is strongly recommended to maintain use of the same imaging 
modality (CT or MRI), acquisition protocol, facility, and scanner across all imaging time 
points per patient.
F 3.2
Clinical examination 
Clinical examination of skin/surface lesions (by visual inspection or manual palpation) will 
not be used for assessment of TLs. Clinically detected lesions can be selected as TLs if they 
are assessed by CT or MRI scans. Clinical examination can be used to assess NTLs in patients 
who also have other lesions assessable by CT, MRI, or plain X-ray and to identify the 
presence of new lesions.

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F 3.3
X-ray
F 3.3.1
Chest X-ray
Chest X-ray assessment will not be used for assessment of TLs. Chest X-ray can, however, be 
used to assess NTL and to identify the presence of new lesions.
F 3.3.2
Plain X-ray 
Plain X-ray may be used as a method of assessment for bone NTL and to identify the presence 
of new bone lesions. 
F 3.4
Ultrasound 
In this study, ultrasound examination will not be used for assessment of TLs and NTLs as it is 
not a reproducible acquisition method (operator dependent), is subjective in interpretation, and 
may not provide an accurate assessment of true tumor size. Ultrasound examination can, 
however, be used to identify the presence of new lesions. Tumors identified by ultrasound will 
need to be assessed by correlative CT or MRI anatomical scan.
F 3.5
Endoscopy and laparoscopy 
Endoscopy and laparoscopy will not be used for tumor assessments as they are not validated 
in the context of tumor assessment.
F 3.6
Tumor markers 
Tumor markers on cytological or histological (biopsy) samples will not be used for tumor 
response assessments as per RECIST v1.1. 
F 3.7
Histology and cytology
Histology on tumor biopsy samples will not be used as part of the tumor response assessment 
as per RECIST v1.1. 
Results of cytological examination for the neoplastic origin of any effusion (e.g., ascites, 
pericardial effusion, pleural effusion) that appears or worsens during the study will not be 
used as part of the tumor response assessment in this study. An effusion that appears or 
significantly worsens (from trace to large) radiologically by CT/MRI anatomical scans will be 
considered to be disease progression due to new lesions or progression of NTLs, respectively. 
F 3.8
Isotopic bone scan 
Bone lesions identified on an isotopic bone scan at baseline and confirmed by CT, MRI, or 
X-ray at baseline should be recorded as NTLs and followed by the same method as per 
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Isotopic bone scans may be used as a method of assessment to identify the presence of new 
bone lesions at follow-up visits. New lesions may be recorded in case positive hot-spots 
appear on a bone scan that were not present on a previous bone scan, however, a newly 
observed equivocal hot-spot on a bone scan that cannot be verified with correlative imaging 
(CT, MRI, X-ray) of the same anatomical region shall not be the only trigger for a progressive 
disease assessment at that time point.
F 3.9
FDG-PET/CT
18F-Fluoro-deoxyglucose positron emission tomography/computed tomography 
(FDG-PET/CT) scans may be used as a method for identifying new lesions, according to the 
following algorithm: New lesions will be recorded where there is positive 
18F-Fluoro-deoxyglucose uptake4 not present on baseline or prior FDG-PET scan, or in a 
location corresponding to a new lesion on CT/MRI at the same follow-up visit. If there is no 
baseline or prior FDG-PET scan available, and no evidence of new lesions on CT/MRI scans, 
then follow-up CT/MRI assessments should be continued, scheduled as per protocol or 
clinical indicated, in order to verify new lesions.
At present, low dose or attenuation correction CT portions of a combined FDG-PET/CT scan 
are of limited use in anatomically-based efficacy assessments, and it is therefore suggested 
that they should not substitute for dedicated diagnostic contrast-enhanced CT scans for tumor 
measurements by RECIST v1.1. In exceptional situations, if a site can document that the CT 
performed, as part of a PET/CT examination, is of identical diagnostic quality (with IV 
contrast) to a dedicated diagnostic CT scan, the CT portion of the PET/CT can be used for 
RECIST v1.1 tumor assessments. Caution: This is not recommended because the PET portion 
of the CT introduces additional (PET) data that may bias an investigator if it is not routinely or 
serially performed.
F 4
Tumor Response Evaluation 
F 4.1
Schedule of evaluation
The methods of assessment of tumor burden used at baseline CT/MRI scans of the chest and 
abdomen (including the entire liver and both adrenal glands) must be used at each subsequent 
                                               
4 A positive FDG-PET scan lesion should be reported only when uptake is greater than approximately twice that 
of the surrounding tissue or liver.

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follow-up assessment. Additional imaging may be performed based on the signs and 
symptoms of the patient (e.g., new lesions at follow-up).
The baseline scan for this study must be done within 21 days prior to Day 1 of Cycle 1 and 
ideally should be performed as close as possible to the start of investigational product. The 
patient’s diagnostic scan can be used as the baseline scan if it complies with recommended 
Image Acquisition Guidelines for assessing tumor burden in the chest and abdomen (including 
liver and adrenal glands) within 28 days prior to Cycle 1 Day 1. The scan performed to 
confirm eligibility for the maintenance phase must be performed within 1 week prior to 
. 
Efficacy for all patients will be assessed by objective tumor assessments every 6 weeks 
(Q6W) ± 1 week, for the first 36 weeks (relative to the date of first dose of study intervention 
in the induction phase; see Section 1.3 and Section 8.1), then every 8 weeks (Q8W) ± 1 week 
thereafter until objective disease progression as defined by RECIST v1.1 (irrespective of the 
reason for stopping treatment/or subsequent therapy). It is important to follow the assessment 
schedule as closely as possible (refer to the SoAs in Table 1, Table 3, and Table 4). Where 
possible, every effort should be made to schedule the scan within 1 week prior to dosing with 
AZD2811; scan results MUST be reviewed prior to dosing to confirm the absence of disease 
progression. 
For patients who discontinue study drug due to toxicity in the absence of objective 
progression, objective tumor assessments should be continued Q6W ± 1 week for 36 weeks 
(relative to the date of Cycle 1 Day 1), then Q8W ± 1 week until confirmed objective disease 
progression. 
Radiographic progression (PD by RECIST v1.1) requires collection of the subsequent scan no 
earlier than 4 weeks after the prior assessment of PD and no later than the next regularly 
scheduled imaging visit. In patients receiving study treatment beyond the first 
RECIST v1.1-defined PD, if progression is not confirmed with the subsequent scan, they may 
continue on study treatment and continue with imaging assessments on their regular schedule.
If disease progression is suspected, an unscheduled radiological imaging assessment should be 
performed. If an unscheduled assessment was performed and the patient has not progressed, 
every attempt should be made to perform the subsequent assessments at their scheduled visits. 
This schedule is to be followed in order to minimize any unintentional bias caused by some 
patients being assessed at a different frequency than other patients.
Additional assessments will be performed post objective disease progression for patients 
remaining on treatment, or until subsequent cancer therapy according to the clinical study 
protocol.
CCI

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F 4.2
Target lesions
F 4.2.1
Documentation of target lesions
A maximum of 5 measurable lesions, with a maximum of 2 lesions per organ (including 
lymph nodes collectively considered as a single organ), representative of all lesions involved, 
should be identified as TLs at baseline. Target lesions should be selected on the basis of their 
size (longest diameter for non-nodal lesions or short axis diameter for nodal lesions), but in 
addition should be those that lend themselves to reproducible repeated measurements. It may 
be the case that, on occasion, the largest lesion does not lend itself to reproducible 
measurement, in which circumstance the next largest lesion, which can be measured 
reproducibly, should be selected.
The site and location of each TL should be documented as well as the longest diameter for 
non-nodal lesions (or short axis for lymph nodes). All measurements should be recorded in 
millimeters. At baseline, the sum of the diameters for all TLs will be calculated and reported 
as the baseline sum of diameters. At follow-up visits, the sum of diameters for all TLs will be 
calculated and reported as the follow-up sum of diameters.  
Special Cases:
!
For TL measurable in 2 or 3 dimensions, always report the longest diameter. For 
pathological lymph nodes measurable in 2 or 3 dimensions, always report the short axis 
diameter. 
!
If the CT/MRI slice thickness used is > 5 mm, the minimum size of measurable disease at 
baseline should be twice the slice thickness of the baseline scan.
!
If a TL has completely disappeared, the diameter should be recorded as 0 mm for the 
current and all subsequent scans. If a lesion appears in the same location on a subsequent 
scan, it will be recorded as a New Lesion.
!
If a TL splits into 2 or more parts, then record the sum of the diameters of those parts. 
!
If 2 or more TLs merge, then the sum of the diameters of the combined lesion should be 
recorded for one of the lesions and 0 mm recorded for the other lesion(s).  
!
If a TL is believed to be present and is faintly seen but too small to measure, a default 
value of 5 mm should be assigned. If an accurate measure can be given, this should be 
recorded, even if it is below 5 mm.
!
If a TL cannot be measured accurately due to it being too large, provide an estimate of the 
size of the lesion, and the overall visit assessment will be designated as PD. 
!
When a TL has had any intervention, e.g., definitive radiotherapy, embolization, surgery, 
etc., during the study, the size of the TL should still be provided where possible and the 
intervention recorded in the RECIST case report form for that time point and in all 

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subsequent TL assessments (see ‘Not evaluable’ below). If a TL has been completely 
removed (surgery) or disappears following an intervention, the diameter should be 
recorded as 0 mm.
F 4.2.2
Evaluation of target lesions
This section provides the definitions of the criteria used to determine objective tumor visit 
response for TL (Table 25).
Table 25
Evaluation of Target Lesions
Complete response (CR)
Disappearance of all TLs since baseline. Any pathological lymph nodes 
selected as TLs must have a reduction in short axis diameter to < 10 mm
Partial response (PR)
At least a 30% decrease in the sum of the diameters of TL, taking as 
reference the baseline sum of diameters
Stable disease (SD)
Neither sufficient decrease in sum of diameter to qualify for PR nor 
sufficient increase to qualify for PD
Progression of disease 
At least a 20% increase in the sum of diameters of TLs, taking as 
reference the smallest previous sum of diameters (nadir) - this includes 
the baseline sum if that is the smallest on study. In addition to the 
relative increase of 20%, the sum must also demonstrate an absolute 
increase of at least 5 mm from nadir.
Not evaluable (NE)
Only relevant if any of the TLs at follow-up were not assessed or not 
evaluable (e.g., missing anatomy) or had a lesion intervention at this 
visit.
Note: If the sum of diameters meets the progressive disease criteria, 
progressive disease overrides not evaluable as a TL response
CR = Complete response; PR = Partial response; PD = Progressive disease; NE = Not evaluable; SD = Stable 
disease; TL = Target lesion.
F 4.3
Non-target lesions
F 4.3.1
Evaluation of non-target lesions
All other lesions (or sites of disease) not recorded as TL should be identified as NTL at 
baseline. Measurements are not required for these lesions, but their status should be followed 
at subsequent visits. At each visit, an overall assessment of the NTL response should be 
recorded by the . This section provides the definitions of the criteria used to determine and 
record overall response for NTL at the investigational site at each visit (Table 26).

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Table 26
Evaluation of Non-target Lesions
Complete response (CR)
Disappearance of all NTLs since baseline. All lymph nodes must be non-
pathological in size (< 10 mm short axis).
Non-CR/non-PD
Persistence of one or more NTL.
Progression 
Unequivocal progression of existing NTLs. Unequivocal progression 
may be due to an important progression in one lesion only or in several 
lesions. In all cases, the progression MUST be clinically significant for 
the physician to consider changing (or stopping) therapy.
Not evaluable (NE)
Only relevant when one or some of the NTLs were not assessed and, in 
the investigator’s opinion, they are not able to provide an evaluable 
overall NTL assessment at this visit.
Note: For patients without TLs at baseline, this is relevant if any of the 
NTLs were not assessed at this visit and the progression criteria have not 
been met.
CR = Complete response; PR = Partial response; PD = Progressive disease; NE = Not evaluable; NTL = Non-
target lesion; TL = Target lesion.
To achieve ‘unequivocal progression’ on the basis of NTLs, there must be an overall level of 
substantial worsening in non-target disease such that, even in presence of stable disease or 
partial response in TLs, the overall tumor burden has increased sufficiently to merit 
discontinuation of therapy. A modest increase in the size of one or more NTLs is usually not 
sufficient to qualify for unequivocal progression status.
F 4.4
New lesions
Details of any new lesions will also be recorded with the date of assessment. The presence of 
one or more new lesions is assessed as progression. 
The finding of a new lesion should be unequivocal: ie, not attributable to differences in 
scanning technique, change in imaging modality, or findings thought to represent something 
other than a tumor.
If a new lesion is equivocal, e.g., because of its small size, the treatment and tumor 
assessments should be continued until the previously new lesion has been assessed as 
unequivocal and then the progression date should be declared using the date of the initial scan 
when the new lesion first appeared.
A lesion identified at a follow-up assessment in an anatomical location that was not scanned at 
baseline is considered a new lesion and will indicate disease progression.

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F 4.5
Symptomatic deterioration
Symptomatic (clinical) deterioration is not a descriptor of an objective response: It is a reason 
for stopping study therapy.
Patients with ‘symptomatic deterioration’ requiring discontinuation of treatment without 
objective radiologic evidence of disease progression at that time should continue to undergo 
tumor assessments where clinically feasible.
F 4.6
Evaluation of overall visit response
The overall visit response will be derived using the algorithm shown in Table 27.
Table 27
Overall Visit Response
Target lesions
Non-target lesions
New lesions
Overall response
CR
CR
No
CR
CR
NA
No
CR
NA
CR
No
CR
CR
Non-CR/Non-PD 
No
PR
CR
NE
No 
PR
PR
Non-PD or NE
No
PR
SD 
Non-PD or NE
No
SD
NA
Non-CR/Non-PD
No
SD (Non-CR/non-PD)
NE
Non-PD or NE
No
NE
NA
NE
No
NE
NA
NA
No 
NED
PD
Any
Yes or No
PD
Any
PD
Yes or No
PD
Any
Any
Yes
PD
CR = Complete response; NA = Not applicable (relevant when no TLs or NTLs are present at baseline); NE = 
Not evaluable; NED = No Evidence of Disease (relevant when neither TLs nor NTLs are present at baseline); 
NTL = Non-target lesion; PD = Progressive disease; PR = Partial response; SD = Stable disease; TL = Target 
lesion. 
F 5
Confirmation of Radiological Progression
A follow-up scan is collected after the initial RECIST v1.1-defined PD, preferably at the next 
(and no later than the next) scheduled imaging visit, and no less than 4 weeks after the prior 
assessment of PD, and the Confirmation of Radiological Progression criteria described below 
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continue to receive study treatment at the discretion of the investigator and patient (following 
consultation with AstraZeneca) can receive treatment until no longer having clinical benefit.
Confirmation of radiological progression guidelines are set for the following reasons: 
!
For patient management and treatment decisions
!
In the absence of significant clinical deterioration, to promote the collection of additional 
scans after the first radiologic RECIST v1.1 assessment of PD in order to distinguish 
pseudoprogression from true radiologic progression. 
Confirmation of Radiological Progression Criteria:
Confirmation of radiological progression guidelines are used to evaluate scans subsequent to a 
prior radiological PD. An immediate prior RECIST v1.1-defined radiologic PD would be 
considered confirmed if any of the following criteria are met in a subsequent follow-up scan 
(acquired preferably at the next regularly-scheduled imaging visit but no sooner than 4 weeks 
after RECIST v1.1-defined PD scan):
!
≥20% increase in the sum of diameters of TLs compared with the nadir at 2 consecutive 
visits, each with an absolute increase of at least 5 mm in sum of diameters compared to 
nadir (as per RECIST v1.1 definition)
!
and/or significant progression (worsening) of NTLs at the follow-up scan time point 
compared with the immediate prior time point (as per RECIST v1.1 definition) 
!
and/or significant progression (worsening) of pre-existing new lesions at the follow-up 
scan time point compared with the immediate prior time point (Note: Pre-existing new 
lesions are evaluated as NTLs at the confirmatory scan time point)
!
and/or additional (brand) new unequivocal lesions at the follow-up scan time point (as per 
RECIST v1.1 definition).
NOTE: In order to have confirmed radiological progression, there should be 2 consecutive 
assessments meeting the PD definition, the first PD by RECIST v1.1 and the second PD using 
the confirmation of radiological progression criteria (above). If the first assessment fulfilling 
the PD definition by RECIST v1.1 is not confirmed, the patient may continue with 
assessments until the next PD by RECIST v1.1, which will also require a follow-up scan 
evaluated using the Confirmation of Radiological Progression criteria. If the first PD (by 
RECIST v1.1) is not confirmed by the immediate next scan, then the investigator should 
not change the PD assessment of the first scan.

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If a patient discontinues treatment (and/or receives a subsequent anticancer therapy) prior to 
radiologic progression, then the patient should still continue to be followed until objective 
disease progression.
F 6
Central Review
All images will be collected, quality checked, and stored centrally by an Imaging Contract 
Research Organization (CRO) appointed by AstraZeneca. Guidelines for image acquisition, 
storage at the investigative site as source data, and transfer to the imaging CRO will be 
provided in a separate document.
F 7
Specifications for Radiological Imaging
These notes are recommendations for use in clinical studies. The use of standardized protocols 
for CT and MRI allows comparability both within and between different studies, irrespective 
of where the examination has been undertaken. 
If specified, all images will be collected, quality checked, and stored centrally by the imaging 
CRO appointed by AstraZeneca. Guidelines for image acquisition, anonymization, storage at 
the investigative site as source data, and transfer to the imaging CRO will be provided in a 
separate document. The management of patients will be based solely upon the local 
assessments conducted by the investigator.
F 7.1
CT Scan
Computed tomography scans of the chest and abdomen (and pelvis when indicated) should be 
contiguous throughout all the anatomical region of interest.  
The most critical CT image acquisition parameters for optimal tumor evaluation using 
RECIST v1.1 are anatomic coverage, contrast administration, slice thickness, and 
reconstruction interval.
F 7.1.1
Anatomic coverage
Optimal anatomic coverage for most solid tumors is the chest and abdomen (and pelvis if 
indicated). Coverage should encompass all areas of known predilection for metastases in the 
disease under evaluation and should additionally investigate areas that may be involved based 
on signs and symptoms of individual patients. Because a lesion later identified in a body part 
not scanned at baseline would be considered as a new lesion representing disease progression, 
careful consideration should be given to the extent of imaging coverage at baseline and at 
subsequent follow-up time points. This will enable better consistency not only of tumor 
measurements but also identification of new disease.

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F 7.1.2
Contrast administration
Optimal visualization and measurement of metastases in solid tumors requires consistent 
administration (dose and rate) of IV contrast as well as timing of scanning. Typically, most 
abdominal imaging is performed during the portal venous phase and (optimally) about the 
same time frame after injection on each examination. An adequate volume of a suitable 
contrast agent should be given so that the metastases are demonstrated to best effect and a 
consistent method is used on subsequent examinations for any given patient. It is very 
important that the same technique be used at baseline and on follow-up examinations for a 
given patient. For patients who develop contraindications to contrast after baseline contrast 
CT is done, the decision as to whether non-contrast CT or MRI (enhanced or non-enhanced) 
should be performed should also be based on the tumor type, anatomic location of the disease, 
and should be optimized to allow for comparison to the prior studies if possible. Each case 
should be discussed with the radiologist to determine if substitution of these other approaches 
is possible and, if not, the patient should be considered not evaluable from that point forward. 
Care must be taken in measurement of TLs on a different modality and interpretation of non-
target disease or new lesions, since the same lesion may appear to have a different size using a 
new modality. Oral contrast is recommended to help visualize and differentiate structures in 
the abdomen.
If iodine contrast media is medically contraindicated at baseline or at any time during the 
course of the study, then the recommended methods are: CT thoracic (Fry et al, 2016)
examination without contrast and abdominal (and pelvis) MRI with contrast. If MRI cannot be 
performed, then CT without IV contrast is an option for the thorax and abdomen (and pelvis 
examination). For brain imaging, MRI with IV contrast is the preferred method.
F 7.1.3
Slice thickness and reconstruction interval
It is recommended that CT scans be performed at 5 mm contiguous slice thickness, and this 
guideline presumes a minimum 5 mm thickness in recommendations for the measurable lesion 
definition. Exceptionally, particular institutions may perform medically acceptable scans at 
slice thicknesses greater than 5 mm. If this occurs, the minimum size of measurable lesions at 
baseline should be twice the slice thickness of the baseline scans.
All window settings should be included in the assessment, particularly in the thorax where 
lung and soft tissue windows should be considered. When measuring lesions, the TL should 
be measured on the same window setting for repeated examinations throughout the study. All 
images from each examination should be included in the assessment and not “selected” 
images of the apparent lesion.

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F 7.2
MRI Scan
Magnetic resonance imaging has excellent contrast, spatial, and temporal resolution; however, 
there are many image acquisition variables involved in MRI, which greatly impact image 
quality, lesion conspicuity, and measurement. Furthermore, the availability of MRI is variable 
globally. The modality used at follow-up should be the same as was used at baseline and the 
lesions should be measured/assessed on the same pulse sequence. Generally, axial imaging of 
the abdomen and pelvis (and other anatomies, e.g., neck) with T1 and T2 weighted imaging 
along with gadolinium-enhanced imaging can be performed. The field of view, matrix,
number of excitations, phase encoding steps, use of fat suppression, and fast sequences should 
be optimized for the specific body part being imaged as well as the scanner utilized. 
Computed tomography of the chest is typically recommended over MRI due to significant 
motion artifacts (heart, major blood vessels, and breathing) associated with MRI. It is beyond 
the scope of this appendix to prescribe specific MRI pulse sequence parameters for all 
scanners, body parts, and diseases. Ideally, the same type of scanner should be used and the 
image acquisition protocol should be followed as closely as possible to prior scans. Body 
scans should be performed with breath-hold scanning techniques if possible. 
For these reasons, CT is the imaging modality of choice.
F 8
REFERENCES
Eisenhauer et al 2009
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):228-47.  

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Appendix G
Patient-Reported Outcomes: EORTC QLQ-C30, EORTC 
QLQ-LC13

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Appendix H
Changes Related to Mitigation of Study Disruptions Due to 
Cases of Civil Crisis, Natural Disaster, or Public Health 
Crisis
Note: Changes below should be implemented only during study disruptions due to any of or a 
combination of civil crisis, natural disaster, or public health crisis (e.g., during quarantines and 
resulting site closures, regional travel restrictions, and considerations if site personnel or study 
participants become infected with SARS-CoV-2 or similar pandemic infection) during which 
participants may not wish to or may be unable to visit the study site for study visits. These 
changes should only be implemented if allowable by local/regional guidelines and following 
notification from the Sponsor, and instructions on how to perform these procedures will be 
provided at the time of implementation.  
H 1
Reconsent of Study Participants During Study Interruptions 
During study interruptions, it may not be possible for the participants to complete study visits 
and assessments on site and alternative means for carrying out the visits and assessments may 
be necessary, eg, remote visits. Reconsent should be obtained for the alternative means of 
carrying out visits and assessments and should be obtained prior to performing the procedures 
described in Sections H 2 to H 5. Local and regional regulations and/or guidelines regarding 
reconsent of study participants should be checked and followed. Reconsent may be verbal if 
allowed by local and regional guidelines (note, in the case of verbal reconsent the ICF should 
be signed at the participant’s next contact with the study site). Visiting the study sites for the 
sole purpose of obtaining reconsent should be avoided. 
H 2
Rescreening of Participants to Reconfirm Study Eligibility
Additional rescreening for screen failure due to study disruption can be performed in 
previously screened participants. The investigator should confirm this with the designated 
Study Physician.
In addition, during study disruption, there may be a delay between confirming eligibility of a 
participant and either enrollment into the study or commencing of dosing with investigational 
product. If this delay is outside the screening window specified in Section 1.3, the participant 
will need to be rescreened to reconfirm eligibility before commencing study procedures. This 
will provide another opportunity to re-screen a participant in addition to that detailed in 
Section 5.5. The procedures detailed in Section 1.3 must be undertaken to confirm eligibility 
using the same enrollment number as previously assigned to the participant.
H 3
Home or Remote Visit to Replace On-site Visit (where applicable)
A qualified Health Care Professional (HCP) from the study site or third-party vendor (TPV) 
service will visit the participant’s home or other remote location as per local standard 

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operating procedures, as applicable. Supplies will be provided for a safe and efficient visit. 
The qualified HCP will be expected to collect information per the Clinical Study Protocol. If 
applicable, assessments will be performed according to a revised Schedule of Activities.
H 4
Telemedicine Visit to Replace On-site Visit (where applicable)
In this appendix, the term telemedicine visit refers to remote contact with the participants 
using telecommunications technology, including phone calls, virtual or video visits, and 
mobile health devices.
During a civil crisis, natural disaster, or public health crisis, on-site visits may be replaced by 
a telemedicine visit if allowed by local/regional guidelines. Having a telemedicine contact 
with the participants will allow adverse events, concomitant medication, etc to be reported and 
documented. If applicable, safety procedures and blood sample collection will be performed 
according to the revised SoA.
H 5
Data Capture During Telemedicine or Home/Remote Visits
Data collected during telemedicine or home/remote visits will be captured by the qualified 
HCP from the study site or TPV service, or by the participants themselves, e.g., patient 
reported outcomes.
H 6
COVID-19 Risk Assessment 
The safety of participants is of primary importance. Any potential risks of participating in the 
study, particularly with the added challenges due to COVID-19 outbreak, should be weighed 
against the anticipated benefit (see also principle 2.2 of ICH GCP). Investigators are advised 
to use clinical judgment in determining infection prevention precautions for study participants.
The emergence of SARS-CoV-2 presents a potential safety risk for cancer patients. 
Participants enrolling in this study may require more frequent visits to the site for study 
treatment administration and for study assessments compared to participants receiving 
standard of care. Therefore, several risk mitigation factors have been implemented related to 
study conduct during the COVID-19 outbreak, for patient management in an event of 
COVID-19, and actions to be taken on study treatment (see Section H 9). With these measures 
in place, it is considered that the anticipated potential benefits for the participants enrolled in 
this study outweigh the potential risks. All implemented measures prioritise trial participant 
safety and data validity; in case these two conflict with each other, trial participant safety 
should always prevail (see also European Medicines Agency Guidance on the management of 
clinical trials during the COVID-19 [coronavirus] pandemic [EMA 2020]). 
Notably, participants with active COVID-19 infection confirmed by local laboratory testing
will not be eligible for study enrolment (see CSP Section 5.2, Exclusion Criterion 1). 

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H 7
Potential Risks during COVID-19
Every effort should be made to follow the CSP. Section H 10 provides a dose modification 
and management plan for participants with confirmed or suspected COVID-19 who are being 
treated with study intervention durvalumab. The risk-benefit assessment should be carefully 
considered for each participant enrolling in the study based on the known safety risks related 
to COVID-19, individual needs, and local guidelines and restrictions. Investigators must 
continue to use their best clinical judgment in determining the most optimal care for 
participants and utmost diligence in determining their eligibility for study participation, 
continued study treatment, and overall assessment of benefit/risk of study treatment or 
participation.
The sponsor must be promptly notified of a site’s inability to perform study activities due to 
COVID-19 outbreak in order to minimise any potential risks.
H 8
New Participant Enrolment
Study sites may continue to recruit new participants into the study provided the following 
activities to preserve study integrity can be met:
!
Upon discussion with the site monitor, the study site has confirmed the ability to enrol 
and manage new participants effectively and in compliance with the protocol.
!
Data will continue to be entered into the eCRF and queries resolved in a timely manner. 
Per CSP Exclusion Criterion 1 (see CSP Section 5.2), participants with uncontrolled 
intercurrent illness, including but not limited to, ongoing or active infection are not eligible for 
the study participation and hence such participants (including those who have confirmed 
COVID 19) should not be included for study participation.
H 9
Study Treatment Administration
If an AE or SAE is associated with COVID-19, the investigator should determine whether the 
participants’ treatment with investigational product should continue, be interrupted, or be 
discontinued in accordance with the CSP.
AEs, SAEs, cycle delays and/or treatment suspensions associated with COVID-19 along with 
logistical issues should be reported according to the eCRF Completion Guidelines. 
For dosing discontinuations, where applicable, the dosing discontinuation guidelines should 
be followed, and the End of Treatment Form(s) completed

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H 10
Ongoing Participants
Participants receiving study intervention should continue to undergo safety assessments prior 
to dosing in accordance with the CSP. In case it is not feasible to perform safety assessments, 
study intervention should be interrupted until such assessments can be completed.
H 10.1
If a Participant has an Event Suspected to be COVID-19
Delay or omit study intervention as appropriate and test for COVID-19 per local health 
authority or institutional guidance. 
∀
Signs and symptoms of COVID-19 include but are not limited to new onset of fever, 
new or worsening cough, shortness of breath, difficulty breathing and sometimes 
abnormal chest imaging and may be similar to those of an imAE. 
∀
In accordance with the CSP and the TMGs for imAEs, thorough evaluation should be 
performed to accurately identify the underlying pathology in case an AE is 
encountered for a participant. 
∀
If COVID-19 is ruled out, study intervention may be resumed per the CSP.
∀
If COVID-19 is confirmed or diagnosis still suspected after evaluation, manage 
COVID-19 per local guidance until full recovery. 
H 10.2
Participants with Confirmed COVID-19
Participants with confirmed COVID-19 (by local laboratory testing and/or combination of 
key symptoms) should have study intervention withheld and COVID-19 managed per local 
guidance.
In case of confirmed COVID-19 and a simultaneous imAE requiring treatment, investigators 
are advised to apply clinical judgement regarding the use of corticosteroids as per the 
durvalumab/tremelimumab TMGs. This includes also the consideration of alternate 
immunosuppressive agents other than corticosteroids for imAE management, depending on 
the individual participant’s presentation (Curigliano et al 2020).
H 10.3
Restarting Study Intervention
Study intervention must not be resumed until recovery from COVID-19 (eg, confirmed by 
imaging, lab testing and/or absence of symptoms) and COVID-19-specific treatment has been 
completed per local guidance.
The study clinical lead should be contacted if any additional guidance or clarification is 
needed.

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H 10.4
Vaccination Against COVID-19
Protocol restrictions applying to live attenuated vaccines are relevant for live attenuated 
COVID-19 vaccines as well. Investigators should apply their discretion assessing the 
risk-benefit of other types of COVID-19 vaccines for participants in clinical trials. Ideally, 
administration of the vaccine should be done on a different day other than the day of study 
drug administration to differentiate any potential AEs seen from the vaccine and study drug. 
The administration of the vaccine and any potential AEs associated with the vaccine are to be 
documented on the concomitant medication and AE eCRFs, respectively.
H 11
References
Curigliano et al 2020 
Curigliano G, Banerjee S, Cervantes A, Garassino M, Garrido P, Girard N. Managing cancer 
patients during the COVID-19 pandemic: an ESMO multidisciplinary expert consensus. Ann 
Oncol 2020;31(10):1320-35.
EMA 2020
EMA, Clinical Trials Facilitation and Coordination Group, European Commission. Guidance 
on the Management of Clinical Trials during the COVID-19 (Coronavirus) pandemic, 
Version 2, 27 March 2020. Available from: URL: 
https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-
10/guidanceclinicaltrials_covid19_en.pdf. Accessed: 17 December 2020.

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Appendix I
Abbreviations
Abbreviation or special term
Explanation
1L
first line
AE
adverse event
AESI
adverse event of special interest
ALP
alkaline phosphatase
ALT
alanine aminotransferase/transaminase
ANC
absolute neutrophil count
APF6
proportion of participants alive and progression free at 6 months from  
treatment assignment(ie, PFS rate at 6 months)
APF9
proportion of participants alive and progression free at 9 months from  
treatment assignment (ie, PFS rate at 9 months)
APF12
proportion of participants alive and progression free at 12 months from 
treatment assignment (ie, PFS rate at 12 months)
AST
aspartate aminotransferase/transaminase
CD
cluster of differentiation
CI
confidence interval
CL
clearance
CNS
central nervous system
CR
complete response
CRO
Contract Research Organization
CRP
C-reactive protein
CSA
Clinical Study Agreement
CSP
Clinical Study Protocol
CSR
Clinical Study Report
CT
computed tomography
CTCAE
Common Terminology Criteria for Adverse Events
DILI
Drug Induced Liver Injury
DLT
dose-limiting toxicity
DNA
deoxyribonucleic acid 
DoR
duration of response
DUS
disease under study
ECG
electrocardiogram
ECOG
Eastern Cooperative Oncology Group
CCI
CCI
CCI

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Appendix I
Abbreviations
Abbreviation or special term
Explanation
eCRF
electronic Case Report Form
EDC
electronic data capture
EORTC
European Organization for Research and Treatment of Cancer
EOT
end of treatment
EP
etoposide and platinum-based chemotherapy
ePRO
electronic handheld device for participants to record patient-reported 
outcomes
ES-SCLC
extensive-stage small cell lung cancer
EU
European Union
FDA
United States Food and Drug Administration
G-CSF
granulocyte colony stimulating factor
GCP
Good Clinical Practice
HbsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCP
Health Care Professional
HCV
hepatitis C virus
HIV
human immunodeficiency virus
HL
Hy’s Law
HRCT
high-resolution computed tomography
IB
Investigator’s Brochure
ILD
interstitial lung disease
IXRS
interactive voice/web response system
IATA
International Airline Transportation Association
ICF
informed consent form
ICH
International Conference for Harmonisation
IEC
Independent Ethics Committee
imAE
immune-mediated adverse event
IP
investigational product
IRB
Institutional Review Board
IRT
Interactive Response Technology
IV
intravenous
LRV
lower reference value
mAb
monoclonal antibody
CCI

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Appendix I
Abbreviations
Abbreviation or special term
Explanation
MDR
Medical Device Regulation
MedDRA
Medical Dictionary for Regulatory Activities
MRI
magnetic resonance imaging
NCI
National Cancer Institute
NE
not evaluable
NP
nanoparticle
NTL
non-target lesion
ORR
objective response rate
OS
overall survival
OS12, OS15, OS18
participants alive at 12, 15, 18 months
PD
progressive disease
PD-1
programmed cell death-protein 1
PD-L1
programmed cell death-ligand 1
PD-L2
programmed cell death-ligand 2
PEG
polyethylene glycol
PFS
progression-free survival
PFS2
progression-free survival after subsequent anticancer therapy
PHL
Potential Hy’s Law
PI
Principal Investigator 
PK
pharmacokinetic(s)
PNS
paraneoplastic syndrome
PR
partial response
PRO
patient-reported outcomes
PS
performance status
Q6W
every 6 weeks
Q8W
every 8 weeks
QLQ-C30
30-item Core Quality of Life Questionnaire
QLQ-LC13
13-item Lung Cancer Quality of Life Questionnaire
QoL
quality of life
QTcF
Fridericia’s Correction Formula
RECIST
Response Evaluation Criteria in Solid Tumors
RR
respiratory rate
RTSM
Randomization and Trial Supply Management
CCI

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Appendix I
Abbreviations
Abbreviation or special term
Explanation
SAE
serious adverse event 
SAP
statistical analysis plan
SCLC
small-cell lung cancer
SD
stable disease
SoA
Schedule of Activities
SOC
standard of care
SpO2
saturation of peripheral oxygen
SRC
Safety Review Committee
T3
triiodothyronine
T4
thyroxine
TBL
total bilirubin
TEAE
treatment-emergent adverse event
TL
target lesion
TMG
toxicity management guidelines
TPV
third-party vendor
TV
target value
ULN
upper limit of normal
WHO
World Health Organization
CCI

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