A Phase III, double-blind, randomized, placebo-controlled multi-centre, study to assess the efficacy and safety of AZD9291 versus Placebo, in patients with Epidermal Growth Factor Receptor Mutation Positive stage IB-IIIA non-small cell lung carcinoma, following complete tumour resection with or without adjuvant chemotherapy (ADAURA)

1. Provision of informed consent prior to any study specific procedures, sampling, and
analyses
2. Male or female, aged at least 18 years.
3. Histologically confirmed diagnosis of primary non small lung cancer (NSCLC) on
predominantly non-squamous histology
4. MRI or CT scan of the brain must be done prior to surgery as it is considered standard of
care. Patients in whom this was not done prior to surgery may still be enrolled if
appropriate imaging is performed prior to randomization, i.e. MRI or CT of brain.
5. Patients must be classified post-operatively as Stage IB, II or IIIA on the basis of
pathologic criteria. Staging will be according to the TNM staging system for lung cancer
(7th edition)
6. Confirmation by the central laboratory that the tumour harbours one of the 2 common
EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R),
either alone or in combination with other EGFR mutations including T790M.
7. Complete surgical resection of the primary NSCLC is mandatory. All gross disease must
have been removed at the end of surgery. All surgical margins of resection must be
negative for tumour. Resection may be accomplished by open or Video Associated
Thoracic Surgery (VATS) techniques
- Refer to section 4.1.2 for additional guidance
8. Complete recovery from surgery and standard post-operative therapy (if applicable) at the
time of randomization. Treatment cannot commence within 4 weeks following surgery.
No more than 10 weeks may have elapsed between surgery and randomization for patients
who have not received adjuvant chemotherapy; no more than 26 weeks may have elapsed
between surgery and randomization for patients who received adjuvant chemotherapy.
- Complete post-operative wound healing must have occurred following any surgery
- For patients who received post-operative adjuvant platinum-based chemotherapy, a
minimum of 2 weeks must have elapsed (but no more than 10 weeks) from the last
administered dose of chemotherapy to the date of randomization.
Patients must have recovered from all toxicities of prior therapy greater than CTCAE
Grade 1 at the time of starting study treatment with the exception of alopecia and
Grade 2 prior platinum therapy related neuropathy.
9. World Health Organization Performance Status of 0 to 1
10. Female patients should be using adequate contraceptive measures, should not be breast
feeding, and must have a negative pregnancy test prior to first dose of study drug; or
female patients must have an evidence of non-child-bearing potential by fulfilling one of
the following criteria at screening:
- Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12
months following cessation of all exogenous hormonal treatments.
- Women less than50 years old would be consider postmenopausal if they have been
amenorrheic for 12 months or more following cessation of exogenous hormonal
treatments and with luteinizing hormone (LH) and follicle-stimulating hormone (FSH)
levels in the post-menopausal range for the institution.
- Documentation of irreversible surgical sterilisation by hysterectomy, bilateral
oophorectomy, or bilateral salpingectomy but not tubal ligation.
- Male patients should be willing to use barrier contraception, i.e., condoms (see
section3.8).
11. For inclusion in the optional genetics research study, patients must provide informed
consent for genetic research.

1. Previous randomization and treatment in the present study
2. Treatment with any of the following:
- Pre-operative or post-operative or planned radiation therapy for the current lung cancer
- Pre-operative (neo-adjuvant) platinum based or other chemotherapy
- Any prior anticancer therapy
- Prior treatment with neoadjuvant or adjuvant EGFR-TKI at any time
- Major surgery (including primary tumour surgery, excluding placement of vascular access within 4 weeks of the first dose of study drug
- Patients currently receiving (or unable to stop use prior to receiving the first dose of
study treatment) medications or herbal supplements known to be potent inducers of CYP3A4 (at least 3 week
prior)
- Treatment with an investigational drug within five half-lives of the compound or any of its related material.
3. Patients who have had only segmentectomies or wedge resections
4. History of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer, or other solid tumours curatively treated with no evidence of disease for 5 years following the end of treatment.
5. Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of
starting study treatment with the exception of alopecia and Grade 2, prior platinum-therapy
related neuropathy.
6. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled
hypertension and active bleeding diatheses ; or active infection including hepatitis B, hepatitis C and human
immunodeficiency virus (HIV). Active infection will include any patients receiving
intravenous treatment for infection; active hepatitis B infection will, at a minimum, include
all patients who are hepatitis B surface antigen positive (HbsAg positive) based on
serology assessment. Screening for chronic conditions is not required.
7. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of AZD9291.
8. Any of the following cardiac criteria:
- Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 ECGs, using the screening clinic ECG machine-derived QTc value.
- Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG.
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval.
9. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
10. Inadequate bone marrow reserve or organ function as demonstrated by any of the
following laboratory values:.
- Absolute neutrophil count <1.5 x 109 /L.
- Platelet count <100 x 109 /L.
Haemoglobin <90 g/L.
- Alanine aminotransferase (ALT) >2.5x the upper limit of normal (ULN) .
- Aspartate aminotransferase (AST) >2.5xULN.
- Total bilirubin >1.5xULN or >3xULN in the presence of documented Gilbert*s
Syndrome (unconjugated hyperbilirubinaemia).
- Creatinine >1.5xULN concurrent with creatinine clearance <50 mL/min (measured or
calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is
only required when creatinine is >1.5xULN.
11. Women who are breast feeding.
12. History of hypersensitivity to active or inactive excipients of AZD9291 or drugs with a
similar chemical structure or class to AZD9291.;In addition, the following are considered criteria for exclusion from the exploratory genetic
research only:
1. Prior allogeneic bone marrow transplant.
2. Non-leukocyte depleted whole blood transfusion within 120 days of genetic sample
collection.