Study of Osimertinib and Stereotactic Ablative Radiation (SABR) in EGFR Mutant NSCLC

Inclusion Criteria * Written informed consent * Age \> 18 years * Advanced EGFR exon 19 or 21 mutant NSCLC, not amenable to curative surgery or radiotherapy. EGFR mutations may be demonstrated by standard, clinically accepted methods, including direct gene sequencing, PCR, and NextGen sequencing. * World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status 0-2. * Patients must have a life expectancy ≥ 12 weeks. * Females should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test 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 * Male patients should be willing to use barrier contraception. * Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. * At least one lesion, not previously irradiated, that can be accurately assessed at baseline with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements. * Adequate 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 \>9.0 g/dL (transfusion is permitted to achieve Hgb ≥9.0 g/dL) * Alanine aminotransferase \<2.5 times the upper limit of normal (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 hyperbilirubinemia) 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. Exclusion Criteria * Involvement in the planning and/or conduct of the study (applies to both sponsor staff and/or staff at the study site). * Previous treatment with osimertinib or any EGFR TKI. * Previous treatment with immunotherapy or any check point inhibitors. * Treatment with an investigational drug within five half-lives of the compound * 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) (Appendix A). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4. * Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment with the exception of alopecia and grade 2, prior platinum-therapy related neuropathy. * 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. * Patients with symptomatic CNS metastases who are neurologically unstable * Past medical history of ILD, drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD * Any of the following cardiac criteria: * Mean resting corrected QT interval (QTc using Fredericia's formula) \> 470 msec * Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block) * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, 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 * 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 * History of hypersensitivity to osimertinib (or drugs with a similar chemical structure or class to osimertinib) or any excipients of these agents * Males and females of reproductive potential who are not using an effective method of birth control and females who are pregnant or breastfeeding or have a positive (urine or serum) pregnancy test prior to study entry * 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 In addition, the following is considered a criterion for exclusion from the exploratory genetic research: * Previous allogeneic bone marrow transplant. * Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection.