AZD9291 Versus Gefitinib or Erlotinib in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer
- 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
- 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
AstraZeneca Pharmaceuticals LP
- Primary ID D5160C00007
- Secondary IDs NCI-2015-00219, 2014-002694-11, U1111-1160-2242
- Clinicaltrials.gov ID NCT02296125