A Study to Evaluate the Efficacy of Osimertinib With Early Intervention SRS Treatment Compared to the Continuation of Osimertinib Alone, in Patients With EGFR Mutated NSCLC and Asymptomatic Brain Metastases

Inclusion Criteria:

1. Newly diagnosed metastatic NSCLC, not amenable to curative surgery or curativeradiotherapy.
2. Documented EGFR mutation (at any time since the initial diagnosis of NSCLC) known tobe sensitive to Osimertinib - These include exon 19 del; L858R (exon 21); G719X (exon 18); L861G (exon 21); S768I (exon 20) and T790M (exon 20) NOTE: Mutation analysis isto be done as per local practice.
3. An MRI showing brain metastases. At randomization, number of brain lesions is under
4. Patients with over 20 brain lesions at randomization MRI will be suitable forwhole brain radiation, and will not be randomized.
5. Brain metastases are asymptomatic or with minor symptoms (ECOG≤2) at studyrandomization.
6. ECOG performance status ≤2 and a minimum life expectancy of at least 6 months
7. Must be eligible and receive Osimertinib as their anti EGFR TKI at time ofrandomization.
8. Must be eligible for SRS treatment at time of randomization.
9. Provided written informed consent.
10. Be male or female and at least 18 years of age on the day of signing informed consent.
11. Female patients:
12. Willing to use adequate contraceptive measures until 6 weeks after the final doseof study treatment
13. Not breast feeding
14. Have a negative pregnancy test prior to the start of dosing if of childbearingpotential or have evidence of non-childbearing potential by fulfilling one of thefollowing criteria at screening:
15. Post-menopausal, defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments ii. Womenunder 50 years old would be considered postmenopausal if they have beenamenorrheic for 12 months or more following cessation of exogenous hormonaltreatments and with Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) levels in the post-menopausal range for the institution iii. Documentationof irreversible surgical sterilization by hysterectomy, bilateral oophorectomy orbilateral salpingectomy but not tubal ligation
16. Male patients who are willing to use barrier contraception (i.e. condoms) until 4months after the final dose of study treatment.

Exclusion Criteria:

• a. Prior treatment with:

1. Anti EGFR TKI treatment.
2. Checkpoint inhibitors immunotherapy for metastatic NSCLC.
3. Whole brain radiation (WBRT) and/or Stereotactic Radiosurgery (SRS).
4. Medications or herbal supplements known to be potent inducers of CYP3A4 and areunable to stop use within the recommended wash out period prior to receiving thefirst dose of Osimertinib.
5. An investigational drug within five half-lives of the compound.
6. Any other cytotoxic chemotherapy, investigational agents or other anticancerdrugs from a previous treatment regimen or clinical study within 14 days of entryto the study. b. Systemic progression under Osimertinib treatment between screen andrandomization systemic scan, per RECIST1.1. c. Spinal cord compression unless asymptomatic and stable. d. Leptomeningealdisease. e. Moderate or severe symptomatic brain metastases defined as perRadiation Therapy Oncology Group acute morbidity grade 3 to 4. NOTE: Grade 3 refers to neurological findings requiring hospitalization forinitial management. Grade 4 refers to serious neurological impairment includingparalysis, coma or seizures more than three times per week despite medication andrequires hospitalization. f. Any evidence of severe or uncontrolled systemic diseases, includinguncontrolled hypertension and active bleeding diatheses, which in theinvestigator's opinion makes it undesirable for the patient to participate in thetrial or which would jeopardize compliance with the protocol, or active infectionincluding hepatitis B, hepatitis C and human immunodeficiency virus (HIV).Screening for chronic conditions is not required. g. Refractory nausea and vomiting, chronic gastrointestinal diseases, inabilityto swallow the formulated product or previous significant bowel resection thatwould preclude adequate absorption of Osimertinib. h. Involvement in the planning and conduct of the study i. Judgement by theinvestigator that the patient should not participate in the study if the patientis unlikely to comply with study procedures, restrictions and requirements.