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

To assess the efficacy and safety of AZD9291 versus a standard of care epidermal growth factor receptor tyrosine kinase inhibitor in patients with locally advanced or Metastatic Non Small Cell Lung Cancer

Inclusion Criteria

• 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

Exclusion Criteria

• 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 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.
• 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).
• 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.
• 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.
• Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
• Involvement in the planning and/or conduct of the study

This is a Phase III, double-blind, randomised study assessing the efficacy and safety of

AZD9291 (80 mg orally, once daily) versus a standard of care (SoC) Epidermal Growth Factor

Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) (either gefitinib [250 mg orally, once daily]

or erlotinib [150 mg orally, once daily]) in patients with locally advanced or metastatic

Non-small Cell Lung Cancer (NSCLC) that is known to be EGFR sensitising mutation (EGFRm)

positive, treatment-naïve and eligible for first-line treatment with an EGFR-TKI.

Trial Phase Phase III

Trial Type Treatment

Lead Organization
AstraZeneca Pharmaceuticals LP

• Primary ID D5160C00007
• Secondary IDs NCI-2015-00219, U1111-1160-2242, 2014-002694-11
• Clinicaltrials.gov ID NCT02296125