A Study of Osimertinib With or Without Chemotherapy as 1st Line Treatment in Patients With Mutated Epidermal Growth Factor Receptor Non-Small Cell Lung Cancer (FLAURA2)

Inclusion Criteria:

1. Male or female, at least 18 years of age; patients from Japan at least 20 years ofage.

2. Pathologically confirmed non-squamous Non-Small Cell Lung Cancer (NSCLC). NSCLC ofmixed histology is allowed.

3. Newly diagnosed locally advanced (clinical stage IIIB, IIIC) or metastatic Non-SmallCell Lung Cancer (NSCLC) (clinical stage IVA or IVB) or recurrent Non-Small CellLung Cancer (NSCLC) not amenable to curative surgery or radiotherapy.

4. The tumor harbors 1 of the 2 common epidermal growth factor receptor (EGFR)mutations known to be associated with Epidermal growth factor receptor tyrosinekinase inhibitors (EGFR-TKI) sensitivity (Ex19del or L858R), either alone or incombination with other epidermal growth factor receptor (EGFR) mutations, which mayinclude T790M.

5. Patients must have untreated advanced Non-Small Cell Lung Cancer (NSCLC) notamenable to curative surgery or radiotherapy.

6. WHO PS of 0 to 1 at screening with no clinically significant deterioration in theprevious 2 weeks.

7. Life expectancy >12 weeks at Day 1.

8. Willing to use contraception as appropriate during the study and for a period oftime after discontinuing study treatment.

Exclusion Criteria:

1. Spinal cord compression; and unstable brain metastases, with stable brain metastaseswho have completed definitive therapy, are not on steroids, and have a stableneurological status for at least 2 weeks after completion of the definitive therapyand steroids can be enrolled. Patients with asymptomatic brain metastases can beeligible for inclusion if in the opinion of the Investigator immediate definitivetreatment is not indicated

2. Past medical history of Interstitial Lung Disease (ILD), drug-induced InterstitialLung Disease, radiation pneumonitis that required steroid treatment, or any evidenceof clinically active Interstitial Lung Disease.

3. Any evidence of severe or uncontrolled systemic diseases, including uncontrolledhypertension and active bleeding diatheses, which in the Investigator's opinionmakes it undesirable for the patient to participate in the trial or which wouldjeopardize compliance with the protocol, or active infection including Hep. B, Hep.C and HIV. Screening for chronic conditions is not required. Active infection willinclude any patients receiving treatment for infection.

4. QT prolongation or any clinically important abnormalities in rhythm.

5. Inadequate bone marrow reserve or organ function as demonstrated by any of thefollowing laboratory values:

• Absolute neutrophil count below the lower limit of normal (<LLN)

• Platelet count below the LLN

• Hemoglobin <90 g/L. The use of granulocyte colony stimulating factor support,platelet transfusion and blood transfusions to meet these criteria is notpermitted.

• ALT >2.5 x the upper limit of normal (ULN) if no demonstrable liver metastasesor >5 x ULN in the presence of liver metastases

• AST >2.5 x ULN if no demonstrable liver metastases or >5 x ULN in the presenceof liver metastases

• Total bilirubin >1.5 x ULN if no liver metastases or >3 x ULN in the presenceof documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or livermetastases

• Creatinine clearance <60 mL/min calculated by Cockcroft and Gault equation or 24 hour urine collection (refer to Appendix I for appropriate calculation)

6. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability toswallow the formulated product, or previous significant bowel resection that wouldpreclude adequate absorption of osimertinib.

7. Prior treatment with any systemic anti-cancer therapy for advanced Non-Small CellLung Cancer (NSCLC) not amenable to curative surgery or radiation includingchemotherapy, biologic therapy, immunotherapy, or any investigational drug. Prioradjuvant and neo-adjuvant therapies (chemotherapy, radiotherapy, immunotherapy,biologic therapy, investigational agents), or definitive radiation/chemoradiationwith or without regimens including immunotherapy, biologic therapies,investigational agents are permitted as long as treatment was completed at least 12months prior to the development of recurrent disease.

8. Prior treatment with an Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI).

9. Major surgery within 4 weeks of the first dose of investigational product (IP).Procedures such as placement of vascular access, biopsy via mediastinoscopy orbiopsy via video assisted thoracoscopic surgery are permitted.

10. Radiotherapy treatment to more than 30% of the bone marrow or( with a wide field ofradiation within 4 weeks of the first dose of investigational product (IP).

11. History of hypersensitivity to active or inactive excipients of investigationalproduct (IP) or drugs with a similar chemical structure or class to investigationalproduct (IP).