Osimertinib + Chemotherapy for Non-Small Cell Lung Cancer
(FLAURA2 Trial)

Recruiting in Palo Alto (17 mi)

+151 other locations

Overseen byPasi A. Jänne, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Waitlist Available

Sponsor: AstraZeneca

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?The reason for the study is to find out if an experimental combination of an oral medication called osimertinib (TAGRISSO®) when used in combination with chemotherapy is more effective than giving osimertinib alone for the treatment of locally advanced or metastatic non-small cell lung cancer. Some lung cancers are due to mutations in the Deoxyribonucleic acid (DNA) which, if known, can help physicians decide the best treatment for their patients. One type of mutation can occur in the gene that produces a protein on the surface of cells called the Epidermal Growth Factor Receptor (EGFR). Osimertinib is an Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor (TKI) that targets Epidermal Growth Factor Receptor (EGFR) mutations. Unfortunately, despite the benefit observed for patients treated with osimertinib, the vast majority of cancers are expected to develop resistance to the drug over time. The exact reasons why resistance develops are not fully understood but based upon clinical research it is hoped that combining osimertinib with another type of anti-cancer therapy known as chemotherapy will delay the onset of resistance and the worsening of a patient's cancer. In total the study aims to enroll approximately 586 patients, consisting of approximately 30 patients who will participate in a safety run-in component of the trial, and approximately 556 who will receive osimertinib alone or osimertinib in combination with chemotherapy in the main trial. In the main part of the trial there is a one in two chance of receiving osimertinib alone, and the treatment is decided at random by a computer. The study involves a Screening Period, Treatment Period, and Follow up Period. Whilst receiving study medication, it is expected patients will attend, on average, approximately 15 visits over the first 12 months and then approximately 4 visits per year afterwards. Each visit will last about 2 to 6 hours depending on the arrangement of medical assessments by the study centre.

Eligibility Criteria

Adults with untreated advanced non-squamous Non-Small Cell Lung Cancer (NSCLC) that can't be removed by surgery or cured with radiotherapy. They must have a specific EGFR mutation, good performance status, and life expectancy over 12 weeks. Those from Japan must be at least 20 years old. Participants should agree to use contraception and not have had prior treatments for advanced NSCLC.

Inclusion Criteria

My tumor has a specific EGFR mutation sensitive to certain treatments.

Willing to use contraception as appropriate during the study and for a period of time after discontinuing study treatment

My lung cancer is non-squamous NSCLC, possibly with mixed types.

+5 more

Exclusion Criteria

I've had treatments for early-stage lung cancer but none for advanced NSCLC since it recurred.

I have been treated with EGFR-TKI before.

I don't have active spinal issues or unstable brain tumors, and if I had brain treatment, I've been stable for 2 weeks without steroids.

+8 more

Participant Groups

The trial is testing if osimertinib combined with chemotherapy (Pemetrexed/Carboplatin or Pemetrexed/Cisplatin) is more effective than osimertinib alone in treating locally advanced or metastatic NSCLC. Patients are randomly assigned to either treatment group, with visits expected every few months for assessments.

2Treatment groups

Experimental Treatment

Active Control

Group I: Osimertinib 80 mg QD and platinum-based chemotherapyExperimental Treatment2 Interventions

Osimertinib 80 mg in combination with pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) or carboplatin (AUC5) on Day 1 of 21day cycles (every 3 weeks) for 4 cycles, followed by Osimertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks. Dose may be reduced to allow for the management of IP related toxicity.

Group II: Osimertinib 80mg QDActive Control1 Intervention

Osimertinib (AZD9291) 80mg QD. All patients randomized into this will only receive Osimertinib 80mg. Dose may be reduced to allow for the management of IP related toxicity.

Osimertinib is already approved in United States, European Union for the following indications:

🇺🇸 Approved in United States as Tagrisso for:

Locally advanced or metastatic non-small-cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R mutations
Metastatic EGFR T790M mutation-positive NSCLC

🇪🇺 Approved in European Union as Tagrisso for:

Locally advanced or metastatic non-small-cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R mutations
Metastatic EGFR T790M mutation-positive NSCLC