Whole Genomic Landscape of Advanced EGFR-mutant NSCLC

Inclusion Criteria: 1. Provision of informed consent prior to any study specific procedures 2. Male or female must be \> 19 years of age 3. Female subjects should be using highly effective contraceptive measures, and must have a negative pregnancy test and not be breast-feeding prior to start of dosing if of child-bearing potential or must have 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 under 50 years old would be consider postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and 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 4. Male subjects should be willing to use barrier contraception (see Restrictions, Section 3.8) 5. Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy with local confirmation of the presence of EGFR TKI-sensitizing mutation (EGFR exon 19 deletion or L858R mutation), either alone or in combination with other EGFR mutations excluding EGFR exon 20 insertion mutation 6. Mandatory provision of fresh tumor sample before osimertinib via a biopsy or surgical resection 7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 8. Patients must have a life expectancy ≥ 12 weeks. 9. At least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements 10. Provision of informed consent for whole-genome and whole-exome sequencings Exclusion Criteria: 1. Involvement in the planning and/or conduct of the study 2. Previous treatment with an EGFR TKI 3. Patients with different kinds of cancers within 5 years or with malignants simultaneously (except completely cured skin basal cell carcinoma or uterine cervical cancer) 4. Treatment with an investigational drug within five half-lives or 3 months. Patients receiving an radiotherapy targeting brain metastasis or spinal cord compression within 2 weeks before the beginning of study treatment, receiving an wide field radiotherapy over 30% of spinal cord reactivity or who are unrecovered from radiotherapy toxicity 5. Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of CYP3A4 (at least 3 weeks prior). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4 6. 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 7. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required 8. Patients with spinal cord compression, symptomatic or unstable brain metastases except for those patients who have completed definitive therapy and have had a stable neurological status for at least 2 weeks after completion of definitive therapy. Patients who may be on corticosteroids to control brain metastases if they have been on a stable dose for 2 weeks (14 days) prior to the start of study treatment and are clinically asymptomatic are eligible 9. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of osimertinib 10. Any of the following cardiac criteria: * Mean resting corrected QT interval (QTc) \> 470 msec obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derived QTc value * Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block and second degree heart block. * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval and cause Torsades de Pointes. 11. Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease 12. 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 \>2.5 times ULN if no demonstrable liver metastases or \>5 times ULN in the presence of liver metastases; aspartate aminotransferase \>2.5 times ULN if no demonstrable liver metastases or \>5 times ULN in the presence of liver metastases; total bilirubin \>1.5 times ULN if no liver metastases or \>3 times ULN in the presence of documented Gilbert's Syndrome \[unconjugated hyperbilirubinaemia\] or liver metastases; serum creatinine \>1.5 times ULN 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 \>1.5 times ULN 13. History of hypersensitivity to any of the active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib 14. Patients who are pregnant or breast-feeding 15. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements 16. Previous allogeneic bone marrow transplant 17. Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection