Study to Assess the Blood Levels and Safety of AZD9291 in Patients With Advanced Solid Tumours and Normal Liver Function or Mild or Moderate Liver Impairment

Exclusion criteria

• . 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).
• . Treatment in the previous 3 months before dosing in this study with any drug known to have a well-defined potential for fulminant hepatotoxicity (eg, halothane and methotrexate).
• . Treatment with any of the following: an EGFR TKI w/in 8 days or approximately 5x half-life, whichever is the longer, of the first dose of study treatment; Any cytotoxic chemotherapy, investigational agents or other anticancer drugs 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; Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of study treatment, with the exception of patients receiving radiation to more than 30% of the bone marrow or with a wide field of radiation which must be completed within 4 weeks of the first dose of study treatment; 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 inhibitors of CYP3A4 (at least 1 week prior) and potent inducers of CYP3A4 (at least 3 week prior) (Appendix H). All patients in Part B and continued access must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known potent inducer/inhibitory effects on CYP3A4 (Appendix H).
• . 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.
• . 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 final PK sample collection on Day 22.
• . Spinal cord compression or brain metastases unless asymptomatic, stable and not requiring steroids for at least 4 weeks prior to start of study treatment.
• . 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 human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
• . Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: ANCless than1.5x10.9/L; platelet count less than100x10.9/L; haemoglobinless than90 g/L; Creatinine greater than1.5 x institutional ULN concurrent with creatinine clearance less than50 mL/min (measured or calculated by Cockcroft-Gault formula); confirmation of creatinine clearance is only required when creatinine is greater than1.5 x institutional ULN.