Open Label, Prospective Study to Investigate Efficacy and Safety of AZD9291 in BM From NSCLC Patients With EGFR T790M

Inclusion Criteria: 1. Provision of signed and dated written informed consent by the patient or legally acceptable representative prior to any study-specific procedures 2. Metastatic (stage IV) EGFRm NSCLC, not amenable to curative surgery or radiotherapy, with confirmation of the presence of the T790M mutation. 3. For patients with LM: Confirmed diagnosis of LM by positive CSF cytology. Diagnosis by MRI only is not eligible for study entry. At least one site of CNS leptomeningeal disease that can be assessed by magnetic resonance imaging (MRI) and which is suitable for repeat assessments. Measurable CNS or extracranial disease is not required. 4. For patients with measurable BM but without LM: At least one measurable intracranial lesion that, if previously irradiated, has progressed or not responded to radiation therapy, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter by magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements. Measurable extracranial disease is not required. 5. Prior therapy with an EGFR-TKI. Patients may have also received additional lines of treatment. 6. World Health Organization (WHO) performance status 0-2 with no deterioration over the previous 2 weeks and a minimum life expectancy of 3 months. 7. Adequate bone marrow reserve and organ function as demonstrated by complete blood count, biochemistry in blood and urine at baseline. 8. ECG recording at baseline showing absence of any cardiac abnormality as per exclusion criterion #10. 9. Female patients of childbearing potential must be using adequate contraceptive measures (see Restrictions, Section 3.5), must not be breast feeding, and must have a negative pregnancy test prior to start of dosing. Otherwise, they must have evidence of nonchild bearing potential as defined below: 1. Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments 2. Women less than 50 years would be consider post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution 3. Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation 10. Male patients must be willing to use barrier contraception, i.e., condoms. Exclusion Criteria: Subjects should not enter the study if any of the following exclusion criteria are fulfilled: 1. Previous (within 6 months) or current treatment with AZD9291 2. Patients currently receiving (or unable to stop use at least 1 week prior to receiving the first dose of AZD9291) any treatment known to be potent inhibitors or inducers of cytochrome P450 (CYP) 3A4 (Appendix B) 3. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, active infection\* including hepatitis B, hepatitis C and human immunodeficiency virus, or significantly impaired bone marrow reserve or organ function, including hepatic and renal impairment, which in the investigator's opinion would significantly alter the risk/benefit balance. \* active infection will include any patients receiving intravenous treatment for any infection and patients with hepatitis B or C surface antigen (+) - Patients receiving oral antiviral suppressive therapy for hepatitis B or C will be permitted to enrol in the study. 4. Patient with symptomatic central nervous system (CNS) metastases who is neurologically unstable or has required increasing doses of steroids to manage CNS symptoms within the 2 weeks prior to start AZD9291 administration. 5. Prior whole brain radiation therapy. 6. Known intracranial hemorrhage which is unrelated to tumor. 7. For patients with LM and/or BM, CNS complications that require urgent neurosurgical intervention (e.g. resection or shunt placement). 8. For patients with LM, inability to undergo collection of CSF. 9. Past medical history of ILD, drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD 10. Any of the following cardiac criteria: 1. Mean resting corrected QT interval (QTcF) \> 470 ms using Fredericia's formula : 2. 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) 3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events 11. Any unresolved toxicity from prior therapy CTCAE \> grade 3 at the time of starting treatment 12. History of hypersensitivity to excipients of AZD9291 or to drugs with a similar chemical structure or class to AZD9291 13. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: * Absolute neutrophil count \< 1.5 x 10\^9/L * Platelet count \< 100 x 10\^9/L * Haemoglobin \< 90 g/L * 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. Total bilirubin \>3 times the ULN in patients with documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia) or in the presence of liver metastases * 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. * If bone metastases are present and liver function is otherwise considered adequate by the investigator then elevated ALP will not exclude the patient.