Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors, AZD3759 or AZD9291, in Patients Who Have Advanced Non-Small Cell Lung Cancer

1. Obtained written informed consent

2. Male or female aged at least 18 years. Aged at least 20 if Japanese.

3. Histologically or cytologically confirmed diagnosis of NSCLC with single activating EGFR mutations (L858R or Exon19Del).

4. Eastern Cooperative Oncology Group performance status of 0 to1. For LM patients, 0 to 2 is acceptable.

5. In Part A, prior treatment with at least one line of a single agent EGFR TKI and at least 1 line of chemotherapy.

6. In Part B-BM expansion, patients must have not received any EGFR TKI and have asymptomatic brain metastasis, either found during screening process which does not require local treatment in the opinion of the investigator or local treatment has been given (surgery or radiation), patient must be stable without corticosteroid and/or anti-convulsants treatment for at least 2 weeks before study enrollment. For Part B-LM expansion, patients who received previous EGFR TKI treatment must have stable extracranial disease;EGFR TKI treatment naïve patients can also be enrolled into AZD9291 cohorts, or AZD3759 cohorts if efficacy signal seen in Part A and agreed by Safety Review Committee.

7. For patients with neither LM nor measurable BM: At least one measurable extracranial lesion. For patients with measurable BM but without LM: at least one measurable intracranial lesion

8. For patients with LM: Confirmed diagnosis of LM by positive CSF cytology.

9. Male patients should be willing to use barrier contraception, i.e., condoms, until 3 months after last study drug is taken.

10. Females should agree to use 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

11. In Part B-AZD9291 LM expansion (sub-cohort of T790M+ LM patients), patients must have central confirmation of T790M+ mutation status from a sample taken after documented progression on the last treatment administered prior to enrolling in the study. Patients must have received prior therapy with an EGFR TKI and may also have received additional lines of treatment. Stable extracranial disease is not required.

What this study is about