Study to Assess the Effect of Rifampicin on Blood Levels and Safety of AZD9291, in Patients With EGFRm+ NSCLC

For inclusion in the study patient should fulfil the following criteria: 1\. Male or female, aged at least 18 years. 2. Histological or cytological confirmation diagnosis of NSCLC. 3. Radiological documentation of disease progression while on a previous continuous treatment with an EGFR TKI, eg gefitinib, erlotinib or afatinib. In addition, other lines of therapy may have been given. All patients must have documented radiological progression on the last treatment administered prior to enrolling in the study. 4\. Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q). 5\. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 with no deterioration over the previous 2 weeks (Appendix G). 6\. Patients must have a life expectancy of ≥12 weeks as estimated at the time of screening. 7\. Females should be using adequate contraceptive measures 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 amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments. Women under 50 years old would be considered post-menopausal if they have been amenorrhoeic 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. 8\. Male patients should be willing to use barrier contraception, ie, condoms, until 6 months after last study drug is taken. 9\. Contact lens wearers must be prepared to not wear contact lenses and wear glasses for the duration of the rifampicin dosing. 1. Participation in another clinical study with an IP during the last 14 days (or a longer period depending on the defined characteristics of the agents used). 2. Treatment with any of the following: Treatment with an EGFR TKI (eg, erlotinib or gefitinib) w/in 8 days or approx. 5 x half-life, whichever is the longer, of the first dose of study treatment; any cytotoxic chemo, investigational agents or other anticancer drugs from a previous treatment regimen w/in 14 days of the first dose of study treatment; major surgery (excluding placement of vascular access) w/in 4 weeks of the first dose of study treatment; radiotherapy with a limited field of radiation for palliation w/in 1 week of the first dose of study treatment, with the exception of patients receiving radiation to more than 30% of bone marrow or with a wide field of radiation which must be completed w/in 4 weeks of the first; patients currently receiving (or unable to stop use prior to receiving the first dose) medications or herbal supplements known to be potent inhibitors of CYP3A4 (at least 1 week prior) and potent inducers of CYP3A4 (at least 3 week prior). All patients must avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer/inhibitory effects on CYP3A4. 3. 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. 4. Any intake of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade, or other products containing grapefruit or Seville oranges within 7 days of the first administration of the IP until the final PK sample collection on Day 78 of Part A. 5. Spinal cord compression or brain metastases unless asymptomatic, stable and not requiring steroids for at least 4 weeks prior to start of study treatment. 6. 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 study or which would jeopardise compliance with the protocol, or active infection including hepatitis B, hepatitis C and HIV. Screening for chronic conditions is not required. 7. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: ANC \<1.5 x 10\^9/L; Platelet count \<100 x 10\^9/L; Haemoglobin \<90 g/L; ALT \>2.5 times the ULN if no demonstrable liver metastases or \>5 times ULN in the presence of liver metastases; AST \>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; 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. 8. Any of the following cardiac criteria: Mean resting corrected QT interval corrected for heart rate using Fridericia's correction factor (QTcF) \>470 msec obtained from 3 electrocardiograms (ECGs); any clinically important abnormalities in rhythm, conduction or morphology of resting ECG eg, complete left bundle branch block, third degree heart block, second degree heart block, PR interval \>250 msec; 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 or any concomitant medication known to prolong the QT interval. 9. Patients unable to swallow oral medication or patients with GI disorders or significant GI resection likely to interfere with the absorption of AZD9291. 10. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD. 11. Women who are breastfeeding. 12. Patients with a known hypersensitivity to AZD9291 or rifampicin or any of the excipients of the products. 13. Concomitant medication contraindicated for use with rifampicin (including, but not limited to): cisapride, oral midazolam, nisoldipine, pimozide, quinidine, dofetilide, triazolam, levacetylmethadol (levomethadyl), 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA)-reductase inhibitors metabolised by CYP3A4, such as lovastatin and simvastatin, ergot alkaloids metabolised by CYP3A4, such as dihydroergotamine, ergometrine (ergonovine), ergotamine and methylergometrine (methylergonovine). 14. For optional genetic research: .Previous allogenic bone marrow transplant or Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection.