A Global Study to Assess the Effects of MEDI4736 (Durvalumab), Given as Monotherapy or in Combination With Tremelimumab Determined by PD-L1 Expression Versus Standard of Care in Patients With Locally Advanced or Metastatic Non Small Cell Lung Cancer

The study has an umbrella design with 2 sub-studies in: sub-study A (randomizing patients
with PD-L1 positive tumours 1:1 into MEDI4736 (durvalumab) vs. Standard of Care) and
sub-study B (randomizing patients with PD-L1 negative tumours 2:3:1:2 into MEDI4736
(durvalumab) vs. MEDI4736 (durvalumab) plus tremelimumab vs. tremelimumab vs. Standard of
Care. Two substudies may have different duration of recruitment period due difference in
patients population (PD-L1 expression). They may not run concurrently with start and
completion of recruitment potentially occuring at different time points.

Inclusion Criteria:

- Aged at least 18 years

- Documented evidence of NSCLC (Stage IIIB/ IV disease)

- Disease progression or recurrence after both a platinum-based chemotherapy regimen and
at least 1 additional regimen for treatment of NSCLC

- World Health Organization (WHO) Performance Status of 0 or 1

- Estimated life expectancy more than 12 weeks

Exclusion Criteria:

- Prior exposure to any anti-PD-1 or anti-PD-L1 antibody or anti CTLA4

- Brain metastases or spinal cord compression unless asymptomatic, treated and stable
(not requiring steroids)

- Active or prior documented autoimmune disease within the past 2 years

- Evidence of severe or uncontrolled systemic disease, including active bleeding
diatheses or active infections including hepatitis B, C and HIV

- Any unresolved toxicity CTCAE (Common Terminology Criteria of Adverse Events) >Grade 2
from previous anti-cancer therapy

- Known EGFR TK activating mutations or ALK rearrangements

- Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous
immunotherapy agent, or any unresolved irAE >Grade 1

- Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative
colitis)