AZD9291 Versus Gefitinib or Erlotinib in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer

Prior treatment

• Any concurrent and/or other active malignancy that has required treatment within 2 years of first dose of study drug.
• Spinal cord compression, symptomatic and unstable brain metastases, except for those patients who have completed definitive therapy, are not on steroids, have a stable neurologic status for at least 2 weeks after completion of the definitive therapy and steroids.
• Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of AZD9291.

Other illness

• Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses; or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV).
• Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.

Lab values

• Treatment with any of the following:
  • Prior treatment with any systemic anti-cancer therapy for locally advanced/metastatic NSCLC.
  • Prior treatment with an EGFR-TKI.
  • Major surgery within 4 weeks of the first dose of study drug.
  • Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug.
  • Patients currently receiving medications or herbal supplements known to be potent inducers of cytochrome P450 (CYP) 3A4.
  • Alternative anti-cancer treatment
  • Treatment with an investigational drug within five half-lives of the compound or any of its related material.
• Any of the following cardiac criteria:
  • Mean resting corrected QT interval (QTc) \>470 msec, obtained from 3 ECGs, using the screening clinic ECG machine-derived QTcF value.
  • Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG.
  • Any patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval.

Other

• Involvement in the planning and/or conduct of the study

• Male or female, aged at least 18 years.
• Pathologically confirmed adenocarcinoma of the lung.
• Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy.
• The tumour harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R).
• Mandatory provision of an unstained, archived tumour tissue sample in a quantity sufficient to allow for central analysis of EGFR mutation status.
• Patients must be treatment-naïve for locally advanced or metastatic NSCLC and eligible to receive first-line treatment with gefitinib or erlotinib as selected by the participating centre. Prior adjuvant and neo-adjuvant therapy is permitted(chemotherapy, radiotherapy, investigational agents).
• Provision of informed consent prior to any study specific procedures, sampling, and analysis.
• World Health Organization Performance Status of 0 to 1 with no clinically significant deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks