BR.31 A Phase III Prospective Double Blind Placebo Controlled Randomized Study of MEDI4736 in Completely Resected Non-Small Cell Lung Cancer

Planned sample size: 1100 patients Current schema Completely resected Stage IB ≥4 cm, II, IIIA NSCLC  REGISTER Central lab determination of PD-L1 status (PD-L1 ≥25% tumours only after 600 patients enrolled) RANDOMIZE* ARM A MEDI4736 20 mg/kg IV Day 1 every cycle q4 weekly Until 1 year from date of first treatment or earlier if disease relapse/new primary malignancy or unmanageable toxicity End of treatment assessments (4 and 12 weeks from date of last infusion) Follow up for disease event and survival** ARM B Placebo * Randomization will be 2:1 to the active treatment arm ** q12 weekly until 2 years from randomization, then q6 months in year 3, then annually until disease event. After disease event follow for survival q6 monthly until 3 years from randomization, then annually. Planned sample size: 1100 patients Stratification: Stage [IB (≥4 cm) vs. II vs. IIIA] Pre-treatment PD-L1 expression [A (≥50%) vs. B (25-49%) vs. C (1-24%) vs. D (<1%)] Adjuvant platinum-based chemotherapy [≥300 mg/m2 cisplatin or equivalent vs. <300 mg/m2 vs. no chemotherapy] Accruing centre Nodal sampling/dissection conducted in accordance with European Society of Thoracic Surgeons (ESTS) guidelines [yes vs. no] Endpoints: Primary endpoint: Disease free survival (DFS) for patients with NSCLC that is PD-L1 positive Secondary endpoints: DFS in all randomized patients, Overall survival (OS) for patients with NSCLC that is PD-L1 positive, OS for all randomized patients, Lung cancer specific survival for patients with NSCLC that is PD-L1 positive and all randomized patients, Adverse effects and tolerability of MEDI4736, Quality of life, Survival benefits participants judge necessary to make adjuvant immunotherapy worthwhile, Economic evaluation (cost effectiveness and cost utility), Evaluation of predictive/prognostic significance of PD-L1 expression, Evaluation of changes in plasma/serum cytokines and other blood and tissue based biomarkers after treatment with MEDI4736 and at disease event, Exploratory pharmacogenomic assays (baseline only)

Significant changes implemented with Amendment #3 Item Prior to Amendment #3 implementation With Amendment #3 implementation Mediastinal nodal sampling according to ESTS guidelines Required Strongly recommended Added as a stratification factor MEDI4736/placebo administration 10 mg/kg q2 weekly for 6 months (13 infusions), then: 20 mg/kg q4 weekly for 6 months (7 infusions) 20 mg/kg q4 weekly for 12 months (13 infusions) Unblinding requests Patients will not be unblinded for information only or to permit participation in another clinical trial On a case-by-case basis and at the request of the treating physician, patients may be unblinded post-progression to determine whether a patient is an appropriate candidate for a standard of care therapy

Active sites – Clinipace Country (Cooperative Group) Number of sites activated Number of sites pending activation China (CTONG) NA 25 (Start April 2017) Hungary (CEEOG) 1 Italy (NCI Naples) 24 Japan (WJOG) 17 3 Poland (CEEOG) 9 Singapore South Korea (KCSG) 10 Taiwan USA Current as of 30 May 2016

Active sites – Cooperative groups Country (Cooperative Group ) Number of sites activated Number of sites pending activation Australia + New Zealand (ALTG) 23 4 Canada (CCTG ) 29 France (IFCT) 48 12 The Netherlands (NVALT) 9 Spain (GECP) 17 OVERALL TOTAL 189 (81%) 44 Current as of 30 May 2016

BR.31 worldwide accrual to 2016May31 Per 15-12-16 Registratie: 417 Randomisatie: 279 Total registrations = 191 Total randomizations = 117

Registrations and Randomizations by Month Current as of 31 May 2016

Site Activity (1) A screen failure log has been implemented to capture data on all patients screened or approached for consent to participate on the BR.31 trial, but who were either found to be ineligible or were unwilling to participate Accrual and screening activity (a registration, randomization or screen failure log entry) was examined for all sites on 02May2016 Sites were divided into 3 categories: Site with activity Sites that have been open for 3-6 months with no activity Sites that have been open for more than 6 months with no activity

Site Activity (3) Country Total Number of Active Sites in Country Number of Sites With No Activity for 3-6 Months Number of Sites With No Activity for >6 Months Australia 21 3 Canada 30 1 France * 46 12 9 Hungary * Italy 25 2 Japan * 17 4 New Zealand Republic of Korea 10 Singapore * Spain * 7 Taiwan United States Total 188 29 * No screen failure survey entries for this country Responses received indicate continued interest in study

Review of Patients

Reported reasons patients have not been registered 513 entries in web-based screen failure log to 31 May 2016

Changes in submitted screen failure reasons over time

Improvements in screening success Screening success = # registered patients x 100% # registered patients + # reported screen failures Attrition = # reported as never going to be randomized x 100% # registered patients

Reasons registered patients were not randomized Number of patients Patient choice 10 Did not meet eligibility criteria or complete pre-randomization tests 8 Creatinine clearance <50mL/min 2 LVEF <50% QTc >470 msec 1 No clean head CT/MRI within protocol timelines ECOG >1 Relapse 5 Intercurrent illness Death 3 Total 28 Current as of 31 May 2016

Trial Management Updates

Patient reimbursement (1) Data from the screen failure log indicated 15% of patients were declining to participate due to expenses associated with travel to the treating site The Canadian investigator community voiced strong support for patient reimbursement and indicated that it could have a positive impact on accrual AstraZeneca provided C$1.1M (C$1000 per randomized patient) for patient reimbursement program Implemented in March 2016

Significant changes planned for Amendment #4 Item Prior to Amendment #4 implementation With Amendment #4 implementation Reason for change Dose modifications and consent risks Various Update To reflect latest AstraZeneca durvalumab protocols Sub-study for pharmacokinetic sampling and immunogenicity testing Add Response to FDA Letter of Advice Address issues related to type I error rates Assessment of amylase and lipase Not required Required Inclusion of CTONG (China) as collaborative group Accrual expansion Lung function tests Arterial blood gas required Accept pulse oximetry Acceptability of results from less invasive test Patients with history of chronic TB Ineligible Only active TB excluded

Status NVALT

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