AZD9291 for Lung Cancer

(FLAURA Trial)

Not currently recruiting at 183 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: Gefitinib, Erlotinib

Must not be taking: CYP3A4 inducers

Disqualifiers: Active malignancy, Uncontrolled hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 18

Duration: 18 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, AZD9291, for individuals with advanced non-small cell lung cancer (NSCLC) that cannot be treated with surgery or radiation. Researchers aim to determine if AZD9291 is more effective and safer than current standard treatments, Erlotinib or Gefitinib, which also target specific lung cancer mutations. Participants will receive either AZD9291 or the standard treatment, with the option to switch to AZD9291 if their cancer progresses. The trial seeks individuals who have not yet received treatment for their advanced lung cancer but have a specific mutation in their cancer cells. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants access to potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you are taking medications or supplements that strongly affect a liver enzyme called CYP3A4. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that AZD9291, also known as osimertinib, has been tested for safety in treating lung cancer patients. Results indicate a manageable safety profile, with side effects usually mild and treatable in medical settings. Common side effects may include mild skin rashes or diarrhea, but these are typically not severe.

For erlotinib and gefitinib, also compared in this trial, previous research has shown they are generally well-tolerated. Some patients might experience mild skin reactions or diarrhea, similar to AZD9291. Overall, the treatments in this trial have been found to be generally safe for patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lung cancer?

AZD9291 is unique because it specifically targets and inhibits the mutated EGFR (epidermal growth factor receptor) often found in lung cancer patients, while sparing the normal EGFR found in healthy cells. This selectivity helps reduce side effects compared to traditional treatments like Erlotinib and Gefitinib, which target both mutated and normal EGFR. Additionally, AZD9291 has shown promise in overcoming resistance to first-generation EGFR inhibitors, offering new hope for patients who no longer respond to standard therapies. Researchers are excited about AZD9291 because it could potentially improve treatment outcomes and quality of life for lung cancer patients by offering a more precise and effective approach.

What evidence suggests that this trial's treatments could be effective for lung cancer?

Research has shown that AZD9291, also known as osimertinib, effectively treats advanced non-small cell lung cancer (NSCLC) in patients with specific genetic changes. One study found that patients with these changes who took AZD9291 lived for an average of 9.6 months without their cancer worsening, giving them more time before progression compared to others. Another study demonstrated that osimertinib remained effective even after other treatments failed, outperforming similar treatments and leading to better patient outcomes. In this trial, participants may receive AZD9291 plus a placebo or standard care treatments such as Erlotinib or Gefitinib plus a placebo for AZD9291. Overall, these findings suggest that AZD9291 is a promising option for those with advanced NSCLC. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with advanced non-small cell lung cancer that can't be treated with surgery or radiation. Participants must have specific EGFR mutations, no prior treatment for metastatic NSCLC, and a good performance status. They should not have severe diseases, uncontrolled heart conditions, or a history of certain lung issues.

Inclusion Criteria

Provision of informed consent prior to any study specific procedures, sampling, and analysis

I can provide a sample of my tumor for EGFR mutation testing.

My lung cancer is confirmed to be adenocarcinoma.

Exclusion Criteria

Your heart's electrical activity (QT interval) is too long when measured on an ECG.

I haven't had extensive radiation to my bone marrow or wide field radiation in the last 4 weeks.

I am receiving a non-standard treatment for my cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AZD9291 or a standard of care EGFR-TKI (gefitinib or erlotinib) as first-line treatment for locally advanced or metastatic NSCLC

18 months

Every 6 weeks for the first 18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Every 12 weeks until progression

Open-label extension (optional)

Participants in the Standard of Care arm may opt to receive open-label AZD9291 after disease progression

What Are the Treatments Tested in This Trial?

Interventions

• AZD9291
• Erlotinib
• Gefitinib

Trial Overview The study tests the effectiveness and safety of AZD9291 compared to standard treatments Erlotinib or Gefitinib in patients with advanced NSCLC. It involves taking either AZD9291 with placebo or one of the standard drugs alone.

How Is the Trial Designed?

Group I: AZD9291+ placebo Experimental Treatment 3 Interventions

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.

Group II: Standard of Care + placebo AZD9291 Active Control 3 Interventions

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).

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Parexel

Industry Sponsor

Trials

322

Recruited

137,000+

Peyton Howell

Parexel

Chief Executive Officer

Master of Healthcare Administration from The Ohio State University, Bachelor of Arts in Health Communications from the University of Illinois

Dr. Austin Smith

Parexel

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Published Research Related to This Trial

ZD1839 ('Iressa') is a selective inhibitor of the epidermal growth factor receptor that effectively blocks cancer cell growth and survival, showing promising results in preclinical studies with various tumor cell lines and human tumor xenografts.

Preliminary phase I trials indicate that ZD1839 is well-tolerated and shows clinical efficacy, especially in non-small cell lung cancer (NSCLC), leading to its ongoing phase III development for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ZD1839 ('Iressa') as an anticancer agent. Baselga, J., Averbuch, SD.[2018]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa1411817

AZD9291 in EGFR Inhibitor–Resistant Non–Small-Cell ... The median progression-free survival was 9.6 months (95% CI, 8.3 to not reached) in EGFR T790M–positive patients and 2.8 months (95% CI, 2.1 to ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11304135/

Real-world efficacy of low dose osimertinib as second-line ... Treatment with low dose osimertinib demonstrated good efficacy and tolerability in EGFR-mutated advanced NSCLC patients who failed first-line treatment.

3. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(25)00367-0/fulltext

Osimertinib plus consolidative radiotherapy for advanced ... To the best of our knowledge, this is the first study to evaluate the efficacy and tolerability of consolidation radiation therapy (RT) ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S246829422500036X

Real-world comparative outcomes of EGFR-TKIs for first- ... This study compared real-world clinical outcomes of 1L osimertinib versus 1st or 2nd generation EGFR-TKIs (1/2G-TKIs) in patients with EGFR+ mNSCLC.

5. jtocrr.org jtocrr.org/article/S2666-3643(24)00090-0/fulltext

The Whole Picture of First-Line Osimertinib for EGFR ... Results. A total of 583 patients received osimertinib. The median progression-free and overall survival were 20.0 (95% confidence interval [CI]: ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5672073/

Osimertinib (AZD9291) decreases programmed death ... Osimertinib (AZD9291) decreases programmed death ligand-1 in EGFR-mutated non-small cell lung cancer cells · Discussion. Osimertinib is a third-generation EGFR- ...

7. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.e21150

Efficacy and safety study of osimertinib in advanced non- ... Osimertinib presents an adequate safety profile for patients with G1, G2 toxicities, generally easy to manage in clinical practice.

8. lungcancerstoday.com lungcancerstoday.com/post/study-provides-safety-data-from-laura-trial-of-osimertinib-in-egfr-mutated-nsclc

Safety Data From LAURA Trial of Osimertinib in EGFR- ... Osimertinib demonstrated a manageable safety profile for the treatment of stage III epidermal growth factor (EGFR)-mutated advanced non-small cell lung cancer ...