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

AstraZeneca

Status and phase: Active, not recruiting; Phase 3

Conditions: Locally Advanced or Metastatic EGFR Sensitising Mutation Positive Non Small Cell Lung Cancer

Treatments: Drug: Erlotinib 150/100 mg; Drug: AZD9291 80 mg/40 mg + placebo; Drug: Placebo Erlotinib 150/100mg; Drug: Gefitinib 250 mg; Drug: Placebo AZD9291 80 mg/ 40 mg; Drug: Placebo Gefitinib 250 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT02296125

D5160C00007

2014-002694-11 (EudraCT Number)

U1111-1160-2242 (Other Grant/Funding Number)

Details and patient eligibility

About

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

Full description

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.

Enrollment: 674 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Male or female, aged at least 18 years.
2. Pathologically confirmed adenocarcinoma of the lung.
3. Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy.
4. The tumour harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R).
5. Mandatory provision of an unstained, archived tumour tissue sample in a quantity sufficient to allow for central analysis of EGFR mutation status.
6. 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).
7. Provision of informed consent prior to any study specific procedures, sampling, and analysis.
8. 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

1. 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.

2. Any concurrent and/or other active malignancy that has required treatment within 2 years of first dose of study drug.

3. 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.

4. 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).

5. 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.

6. 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.

7. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.

8. Involvement in the planning and/or conduct of the study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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674 participants in 2 patient groups

AZD9291+ placebo

Experimental group

Description:

AZD9291 (80 mg or 40 mg orally, once daily) plus placebo Erlotinib (150mg or 100mg orally, once daily) or placebo Gefitinib (250 mg orally, once daily), in accordance with the randomization schedule.

Treatment:

Drug: Placebo Gefitinib 250 mg

Drug: Placebo Erlotinib 150/100mg

Drug: AZD9291 80 mg/40 mg + placebo

Standard of Care + placebo AZD9291

Active Comparator group

Description:

Erlotinib (150 mg or 100 mg orally, once daily) or placebo Gefitinib (250 mg orally, once daily) plus placebo AZD9291 (80 mg or 40 mg orally, once daily), in accordance with the randomisation schedule. Following objective disease progression according to RECIST 1.1, as per investigator assessment, patients who were randomized to Standard of Care arm may have the option to receive open-label AZD9291 (crossover to active AZD9291).

Treatment:

Drug: Placebo AZD9291 80 mg/ 40 mg

Drug: Gefitinib 250 mg

Drug: Erlotinib 150/100 mg