Osimertinib + Chemotherapy for Non-Small Cell Lung Cancer

(FLAURA2 Trial)

Not currently recruiting at 177 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: EGFR-TKIs

Must not be taking: Steroids, Anti-cancer therapy

Disqualifiers: Uncontrolled hypertension, Active infection, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 19

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining the oral medication osimertinib with chemotherapy is more effective than using osimertinib alone for treating non-small cell lung cancer. The focus is on patients whose cancer has specific genetic mutations affecting a protein called EGFR, which can guide treatment choices. The researchers aim to determine if this combination can delay cancer progression. Individuals with newly diagnosed advanced non-small cell lung cancer and specific EGFR mutations might be suitable candidates for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients early access to potentially effective treatments.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on any systemic anti-cancer therapy for advanced Non-Small Cell Lung Cancer, you may need to stop, as prior treatment with such therapies is an exclusion criterion.

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

Research has shown that osimertinib, when used alone, is generally well-tolerated. In earlier studies, about 22% of patients experienced serious side effects, but these were mostly manageable.

When combined with chemotherapy, studies have found osimertinib safe enough for use. While side effects can occur, they are usually manageable. This combination has been used to treat non-small cell lung cancer with good results.

Overall, both treatments have shown promise in terms of safety, making them viable options for those considering participation in this clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Osimertinib with chemotherapy for non-small cell lung cancer because it offers a unique approach to treatment. Unlike standard chemotherapy alone, this combination uses Osimertinib, a targeted therapy that specifically inhibits the EGFR mutation often found in these cancers. This precision targeting can potentially improve effectiveness and minimize side effects compared to traditional chemotherapy. Furthermore, the integration of Osimertinib with platinum-based chemotherapy aims to enhance overall survival rates, providing a promising new avenue for patients who have limited options.

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

Research has shown that combining osimertinib with chemotherapy effectively treats advanced non-small cell lung cancer. In this trial, one group of participants will receive osimertinib with chemotherapy, which studies have found can help patients live for nearly four years on average, the longest survival time reported for this condition. Another group will receive osimertinib alone, which has been shown to control cancer longer than other treatments. Starting treatment with both osimertinib and chemotherapy has led to a much longer time before the cancer worsens compared to using osimertinib alone. These results suggest that the combination might help delay cancer resistance and improve patient outcomes. ^{2 6 7 8 9}

Who Is on the Research Team?

Pasi A. Jänne, MD

Principal Investigator

Dana Farber Cancer Institute, 450 Brookline Avenue, LC4114, Boston, MA 02215, USA

David Planchard, MD

Principal Investigator

Department of Medical Oncology - Institut Gustave Roussy (IGR) - Villejuif - France

Kunihiko Kobayashi, MD

Principal Investigator

Department of Respiratory Medicine, Saitama Medical University International Medical Center, Saitama, Japan

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive osimertinib alone or in combination with chemotherapy

12 months

Approximately 15 visits over the first 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 33 months

Approximately 4 visits per year

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cisplatin
• Osimertinib
• Pemetrexed

Trial Overview 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.

How Is the Trial Designed?

Group I: Osimertinib 80 mg QD and platinum-based chemotherapy Experimental Treatment 2 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 QD Active Control 1 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

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

Published Research Related to This Trial

Osimertinib is an oral medication specifically designed to target the EGFR T790M mutation in advanced non-small cell lung cancer (NSCLC), which helps overcome resistance to previous EGFR TKI therapies.

It received accelerated approval in the USA in November 2015 for patients with metastatic EGFR T790M mutation-positive NSCLC who have progressed after EGFR TKI treatment, and is currently undergoing further development for broader treatment applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib: First Global Approval. Greig, SL.[2022]

Osimertinib (Tagrisso) is a targeted therapy approved by the FDA for patients with metastatic non-small cell lung cancer (NSCLC) who have the EGFR T790M mutation and have progressed after previous treatments.

The drug received special designations from the FDA, including breakthrough therapy and priority review, highlighting its significance in treating resistant forms of NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting the Gatekeeper: Osimertinib in EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. Skoulidis, F., Papadimitrakopoulou, VA.[2022]

Osimertinib is a third-generation EGFR tyrosine kinase inhibitor that effectively targets specific mutations in advanced non-small cell lung cancer (NSCLC), including the T790M mutation, leading to significantly longer progression-free survival compared to first-generation EGFR TKIs like erlotinib or gefitinib.

The benefits of osimertinib in prolonging progression-free survival were consistent across all patient groups, regardless of the type of EGFR mutation or the presence of CNS metastases, and it has a generally manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib as first-line therapy in advanced NSCLC: a profile of its use. Scott, LJ.[2020]

Osimertinib (Tagrisso) is an approved adjuvant treatment for non-small cell lung cancer patients with specific tumor mutations, highlighting its targeted therapeutic approach.

Common side effects of osimertinib include blood-related issues like leukopenia and thrombocytopenia, as well as gastrointestinal and skin reactions, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Adjuvant Drug for Lung Cancer. Aschenbrenner, DS.[2023]

In a study of 240 advanced non-small-cell lung cancer (NSCLC) patients with acquired resistance to EGFR TKIs, 52.9% had the T790M mutation after rebiopsy, highlighting the mutation's prevalence in treatment resistance.

Patients with the T790M mutation who had previously used osimertinib experienced significantly longer post-progression survival (42.6 months) compared to those without osimertinib (18.0 months) or without the mutation (18.8 months), suggesting osimertinib's effectiveness as a standard treatment for T790M-positive NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Progression Survival in Secondary EGFR T790M-Mutated Non-Small-Cell Lung Cancer Patients With and Without Osimertinib After Failure of a Previous EGFR TKI. Chiang, CL., Huang, HC., Shen, CI., et al.[2022]

Osimertinib (TAGRISSO) received accelerated FDA approval for treating metastatic non-small cell lung cancer with the EGFR T790M mutation, showing significant tumor response rates of 57% and 61% in two major trials involving 411 patients.

While osimertinib demonstrated promising efficacy, common side effects included diarrhea (42%) and rash (41%), with 28% of patients experiencing severe adverse events, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib for the Treatment of Metastatic EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. Khozin, S., Weinstock, C., Blumenthal, GM., et al.[2022]

In a retrospective analysis of 32 patients with EGFR T790M-mutant non-small-cell lung cancer, osimertinib showed a 50% objective response rate and a median progression-free survival of 11.3 months, indicating its efficacy in clinical practice.

The median overall survival was 18.3 months, with better outcomes observed in patients without cerebral metastases and those with better performance status, highlighting the importance of these factors in treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of osimertinib in patients with lung adenocarcinoma in clinical practice - the Expanded Drug Access Program in Poland. Knetki-Wróblewska, M., Kowalski, DM., Czyżewicz, G., et al.[2022]

Osimertinib significantly improves disease-free survival (DFS) in adults with completely resected, early-stage EGFR mutation-positive non-small cell lung cancer (NSCLC), as shown in the pivotal ADAURA trial, regardless of prior adjuvant chemotherapy.

The treatment is well tolerated with a manageable safety profile, and it does not negatively impact health-related quality of life, making it a suitable option for adjuvant therapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib: A Review in Completely Resected, Early-Stage, EGFR Mutation-Positive NSCLC. Frampton, JE.[2022]

Osimertinib, an irreversible tyrosine kinase inhibitor, showed excellent activity in treating a 69-year-old man with metastatic EGFR-mutated non-small cell lung cancer, leading to a rapid treatment response despite initial severe pancytopenia.

After experiencing pancytopenia, the patient's dose of osimertinib was reduced from 80 mg to 40 mg daily, which allowed for continued effective treatment without further adverse events, demonstrating the potential for safe dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancytopenia During Osimertinib Treatment in a Patient with EGFR-Mutated Non-Small Cell Lung Cancer. Di Marino, P., Chiapperino, C., Primavera, FC., et al.[2022]

Citations

1. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/TAGRISSO-osimertinib-plus-chemotherapy-demonstrated-a-median-overall-survival-of-nearly-four-years-the-longest-benefit-ever-reported-in-a-global-Phase-III-trial-in-EGFR-mutated-advanced-lung-cancer.html

TAGRISSO® (osimertinib) plus chemotherapy ... TAGRISSO® (osimertinib) plus chemotherapy demonstrated a median overall survival of nearly four years, the longest benefit ever reported in a ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6519771/

Cost‐Effectiveness of Osimertinib in Treating Newly ... Osimertinib as first‐line treatment yielded the greatest health outcomes but is not a cost‐effective strategy for lung cancer in the US and China.

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

Real-world comparative outcomes of EGFR-TKIs for first- ... Patients treated with osimertinib had a prolonged time to progression and longer time maintain the treatment compared to 1/2G-TKI. This real-world evidence is ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2402614

Osimertinib after Chemoradiotherapy in Stage III EGFR- ... The percentage of patients who were alive and progression free at 12 months was 74% (95% CI, 65 to 80) with osimertinib and 22% (95% CI, 13 to ...

5. appliedclinicaltrialsonline.com appliedclinicaltrialsonline.com/view/astrazeneca-s-tagrisso-landmark-overall-survival-benefit-in-non-small-cell-lung-cancer

AstraZeneca's Tagrisso Shows Landmark Overall Survival ... Tagrisso plus chemotherapy survival benefit: Median overall survival (OS) of nearly four years in first-line EGFR-mutated non-small cell lung ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39576954

A Systematic Review and Single-Arm Meta-Analysis Osimertinib was well tolerated with a frequency of grade 3 or more adverse events of 21.77% (95% CI, 6.24 to 43.33). Conclusion: Osimertinib ...

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa2306434

Osimertinib with or without Chemotherapy in EGFR- ... Overall survival was 89% (95% CI, 84 to 92) in the osimertinib–chemotherapy group and 92% (95% CI, 88 to 95) in the osimertinib group at 12 ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.8518

Safety and efficacy of osimertinib plus consolidative ... The primary endpoint was progression-free survival (PFS); secondary endpoints included duration on osimertinib, toxicity, and overall survival ( ...

9. tagrisso.com tagrisso.com/late-stage-egfr-nsclc/about-tagrisso.html

Late-Stage EGFR+ NSCLC | About TAGRISSO In the clinical trial, half the adults who took TAGRISSO alone lived at least 18.9 months without their cancer growing or spreading and half the adults who took ...