A Study to Determine Safety of Durvalumab After Sequential Chemo Radiation in Patients With Unresectable Stage III Non-Small Cell Lung Cancer

This is a Phase II, open-label, multi-centre study to determine safety of a fixed dose of
Durvalumab (MEDI4736) (1500 mg) monotherapy in participants with unresectable Stage III NSCLC
who have not progressed following definitive, platinum-based sCRT. Approximately, 150
participants will be treated with the study drug in Europe and North America. Participants
will be in complete response (CR), partial response (PR), or have stable disease (SD)
following definitive, platinum-based sCRT, as assessed by the Investigator and further
supported by the screening imaging radiological assessment. Participants must not have
progressed following definitive, platinum-based sCRT; radiation therapy must be completed
within 28 days prior to first Investigational product (IP) dose administration. Participants
must have histologically- or cytologically-documented NSCLC and locally-advanced,
unresectable Stage III disease. Participants will be treated with the study drug in 2
cohorts: approximately 120 participants in the World Health Organization/Eastern Cooperative
Oncology Group Performance Status (WHO/ECOG PS) 0 to 1 Cohort and approximately 30
participants in the WHO/ECOG PS 2 Cohort.

Inclusion Criteria:

1. Capable of giving signed informed consent form (ICF), which includes compliance with
the requirements and restrictions listed in the ICF and in this protocol.

2. Provision of signed and dated, written ICF prior to any mandatory study specific
procedures, sampling, and analyses.

3. Provision of signed and dated written genetic informed consent prior to collection of
sample for genetic analysis (optional).

4.18 years or older at the time of signing the ICF. 5. Histologically or cytologically
documented NSCLC with locally advanced, unresectable Stage III disease (according to the
[International Association for the Study of Lung Cancer] {IASLC} Staging Manual Version 8
[IASLC 2016]).

6. Receipt of sCRT which must have been completed within 28 days prior to first IP dose
administration in the study.

7. Participants must not have progressed following platinum-based sCRT, as per
Investigator-assessed RECIST 1.1 criteria.

8. Must have a life expectancy of at least 12 weeks at enrolment. 9. WHO/ECOG PS ≤2. 10.
Adequate organ and marrow function at enrolment as defined below. These parameters should
be achieved without augmentation by growth factors, transfusions, or infusions within 14
days of screening unless required for SoC.

11. Body weight >30 kg at enrolment and first IP dose administration. 12. Male or female.
13. Evidence of post-menopausal status, or negative urinary or serum pregnancy test for
female pre-menopausal participants. Women will be considered post-menopausal if they have
been amenorrheic for 12 months without an alternative medical cause.

Exclusion Criteria:

1. Participants with locally-advanced NSCLC whose disease has progressed following
platinum-based sCRT.

2. Participants who have disease considered for surgical treatment as part of their care
plan, such as Pancoast or superior sulcus tumours.

3. Mixed small-cell lung cancer and NSCLC histology.

4. History of allogeneic organ transplantation.

5. Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [eg, 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, uveitis, etc]).

6. Uncontrolled intercurrent illness, including but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, Interstitial lung disease (ILD), serious chronic
gastrointestinal (GI) conditions associated with diarrhoea, 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.

7. History of another primary malignancy.

8. History of leptomeningeal carcinomatosis.

9. History of active primary immunodeficiency.

10. Active infection including tuberculosis, hepatitis B (known positive hepatitis B
surface antigen [HbsAg] result),hepatitis C virus (HCV), or human immunodeficiency
virus (HIV) (positive HIV 1/2 antibodies). Participants with a past or resolved
hepatitis B virus (HBV) infection (defined as the presence of hepatitis B core
antibody [anti-HBc] and absence of HbsAg) are eligible. Participants positive for
hepatitis C antibody are eligible only if polymerase chain reaction is negative for
HCV ribonucleic acid (RNA).

11. Any unresolved toxicity of National Cancer Institute (NCI) Common Terminology Criteria
for Adverse Event (CTCAE) Grade ≥2 from previous anticancer therapy with the exception
of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.

12. Known allergy or hypersensitivity to durvalumab (MEDI4736) or any of the IP
excipients.

13. Participants who have received cCRT for locally-advanced NSCLC, or who received sCRT
with at least 2 concomitant CRT cycles. Prior surgical resection (ie, Stage I or II)
is permitted.

14. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.

15. Major surgical procedure (as defined by the Investigator) within 28 days prior to the
first dose of IP.

16. Prior exposure to immune-mediated therapy, including but not limited to, other
anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies, excluding therapeutic
anticancer vaccines.

17. Current or prior use of immunosuppressive medication within 14 days before the first
dose of IP.

18. Previous IP assignment in the present study.

19. Concurrent enrolment in another clinical study, unless it is an observational
(noninterventional) clinical study or the follow-up period of an interventional study.

20. Participation in another clinical study with an IP during the 4 weeks prior to the
first IP dose administration.

21. Prior randomisation or treatment in a previous durvalumab (MEDI4736) ± tremelimumab
clinical study regardless of treatment arm assignment.

22. 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 90 days after the last dose of IP.

23. Judgment by the Investigator that the participant is unsuitable to participate in the
study and the participant is unlikely to comply with study procedures, restrictions,
and requirements.

24. Genetic research study (optional):

Exclusion criteria for participation in the optional (DNA) genetic research component of
the study include:

1. Previous allogeneic bone marrow transplant.

2. Non-leukocyte-depleted whole blood transfusion in 120 days of genetic sample
collection.