Osimertinib for Early Stage Non-Small Cell Lung Cancer

(ADAURA2 Trial)

Not currently recruiting at 167 trial locations

Overseen By AstraZeneca Lung Cancer Study Locator Service

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: CYP3A4 inducers

Disqualifiers: Mixed cancer history, Uncontrolled diseases, Prior NSCLC therapy, others

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: Unknown

Duration: 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called osimertinib to determine its effectiveness for people with non-small cell lung cancer (NSCLC). It targets those whose cancer has been fully removed through surgery and who have a specific gene mutation called EGFR. Participants will receive either osimertinib or a placebo to assess if the drug can prevent cancer recurrence. This trial suits individuals who have had complete tumor removal and tested positive for specific EGFR mutations. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking medications or herbal supplements that strongly induce CYP3A4, an enzyme that affects drug metabolism.

Is there any evidence suggesting that osimertinib is likely to be safe for humans?

Research has shown that patients generally tolerate osimertinib well. In past studies, it did not harm the quality of life for users. The safety profile of osimertinib is manageable, allowing control over any side effects. This medication has already received approval for other types of lung cancer, indicating it has passed safety checks for those uses. Overall, existing evidence supports osimertinib as a safe option for treating early-stage non-small cell lung cancer, with manageable side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Osimertinib stands out because it specifically targets and inhibits the mutated epidermal growth factor receptor (EGFR) often found in non-small cell lung cancer (NSCLC) patients. Unlike traditional chemotherapy, which can affect both cancerous and healthy cells, osimertinib is designed for precision, potentially reducing side effects and improving effectiveness. Researchers are excited about its ability to penetrate the central nervous system, offering hope for better management of brain metastases in NSCLC patients.

What evidence suggests that osimertinib might be an effective treatment for early stage non-small cell lung cancer?

Studies have shown that osimertinib, which participants in this trial may receive, is a promising treatment for early-stage non-small cell lung cancer (NSCLC) with specific changes in the EGFR gene. Research indicates that patients generally tolerate it well, and it can effectively target cancer cells with these changes. In more advanced stages of NSCLC, osimertinib has been linked to longer periods without cancer progression. Even at lower doses, osimertinib has demonstrated good effectiveness, especially for patients who did not respond to initial treatments. These findings suggest osimertinib could be a strong option for managing early-stage lung cancer with EGFR mutations. ^{4 6 7 8 9}

Who Is on the Research Team?

Jonathan W. Goldman

Principal Investigator

University of California, Los Angeles

Yasuhiro Tsutani, MD, PhD

Principal Investigator

Kindai University Facility of Medicine

Jie He, MD, PhD

Principal Investigator

The Cancer Institute and Hospital, Chinese Academy of Medical Sciences (CAMS)

Are You a Good Fit for This Trial?

This trial is for adults who've had a complete surgical removal of non-squamous NSCLC and are fully recovered from surgery. They should have stage IA2 or IA3 disease, good performance status, and specific EGFR mutations. Women must use effective contraception; men agree to barrier methods. Exclusions include severe diseases, certain heart risks, prior cancer treatments for NSCLC, or history of interstitial lung disease.

Inclusion Criteria

My lung cancer was completely removed by surgery.

My lung cancer is non-small cell and not squamous type.

I am fully active or able to carry out light work.

Exclusion Criteria

I don't have lasting side effects from previous treatments above mild level.

Any irregularities in your heart's electrical activity when measured at rest.

I have conditions that could affect my heart's rhythm.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive osimertinib or placebo once daily for up to 3 years

3 years

Follow-up

Participants are monitored for disease-free survival and overall survival

Up to 10 years

What Are the Treatments Tested in This Trial?

Interventions

• Osimertinib
• Placebo

Trial Overview The study tests the effects of Osimertinib against a placebo in patients with early-stage non-small cell lung cancer after tumor removal surgery. It aims to see if Osimertinib can prevent cancer recurrence better than no treatment post-surgery.

How Is the Trial Designed?

Group I: Osimertinib Experimental Treatment 1 Intervention

Osimertinib 80mg, orally, once daily (Dose may be reduced to 40 mg once daily if required at the discretion of the investigator)

Group II: Placebo Placebo Group 1 Intervention

Matching placebo for osimertinib, orally, once daily

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 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 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]

The study established an osimertinib-resistant cell line (HCC827/OSIR) from EGFR-sensitive HCC827 cells, demonstrating that these resistant cells have higher resistance to multiple EGFR tyrosine kinase inhibitors compared to the original cells.

Increased expression of IRE1α was identified as a potential mechanism for resistance to osimertinib, and targeting IRE1α with an inhibitor showed promise in reducing the number of viable resistant cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased Expression of IRE1α Associates with the Resistant Mechanism of Osimertinib (AZD9291)-resistant non-small Cell Lung Cancer HCC827/OSIR Cells. Tang, ZH., Su, MX., Guo, X., et al.[2022]

In a phase 2 study involving 210 patients with EGFR Thr790Met-positive non-small-cell lung cancer (NSCLC), osimertinib demonstrated significant efficacy, with 70% of patients achieving an objective response, including 3% with complete responses.

Osimertinib was found to have manageable side effects, although serious adverse events occurred in 25% of patients, with interstitial lung disease being the only fatal event possibly related to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study. Goss, G., Tsai, CM., Shepherd, FA., 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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11609331/

Osimertinib in Early-Stage EGFR-Mutated Non-small Cell ... Despite these challenges, osimertinib emerges as a promising and well-tolerated treatment option for patients with EGFR mutations in early-stage lung cancer.

2. sciencedirect.com sciencedirect.com/science/article/pii/S1525730425000543

Brief Report: The Effectiveness of Osimertinib in Advanced ... We conducted a retrospective study to assess the effectiveness of osimertinib in advanced NSCLC with various ex19del variants.

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

Osimertinib with or without Chemotherapy in EGFR- ... First-line treatment with osimertinib–chemotherapy led to significantly longer progression-free survival than osimertinib monotherapy among patients with EGFR- ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39118879/

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.

5. jto.org jto.org/article/S1556-0864(25)00699-9/fulltext

Overall Survival in EGFR-Mutant Advanced NSCLC ... Despite advances in tyrosine kinase inhibitor treatments, long-term survival of patients with advanced EGFRm NSCLC remains poor.

6. 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 ... Over the past decade, TAGRISSO has consistently delivered strong survival benefits and tolerable safety across all stages of non-small cell lung ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35713772/

A Review in Completely Resected, Early-Stage, EGFR ... Osimertinib adjuvant therapy did not adversely affect health-related quality of life and was generally well tolerated, with a manageable safety ...

8. tagrisso.com tagrisso.com/early-stage-nsclc.html

Treatment for Early-Stage EGFR+ NSCLC Find how TAGRISSO® (osimertinib) helps reduce the risk of lung cancer coming back after surgery in patients with EGFR+ NSCLC. Learn more about testing and ...

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

Osimertinib plus consolidative radiotherapy for advanced ... Osimertinib plus consolidative radiotherapy for advanced EGFR mutant non–small cell lung cancer: a multicentre, single-arm, phase 2 trial. Sagus ...