AZD9291 for Non-Small Cell Lung Cancer

(ADAURA Trial)

Not currently recruiting at 257 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: CYP3A4 inducers, QT prolongers

Disqualifiers: Radiation therapy, Chemotherapy, Other malignancies, others

Stay on Your Current Meds You can continue your current medications while participating

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: 24

Duration: 96 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, AZD9291, to determine its effectiveness for people with non-small cell lung cancer (NSCLC) that has specific genetic changes (EGFR mutations) and has been surgically removed. Participants will receive either the drug or a placebo (a pill with no active drug) to compare effects. The study seeks individuals whose lung cancer has been completely removed through surgery and who have specific genetic markers. As a Phase 3 trial, this study 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 requires that you do not take medications or herbal supplements that are known to strongly affect a specific liver enzyme (CYP3A4). If you are on such medications, you may need to stop them before participating.

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

Research has shown that AZD9291, also known as osimertinib, is generally well-tolerated by patients with non-small cell lung cancer (NSCLC). In one study, patients taking 80 mg of osimertinib daily experienced significant benefits without many severe side effects. Another study found that 84% of patients survived for at least 36 months while on this treatment, indicating its effectiveness and manageability over time.

Additionally, researchers have successfully combined osimertinib with chemotherapy, offering extended survival benefits. This combination has not shown any unexpected safety issues, reassuring those considering the treatment.

Since AZD9291 is being studied in a late-phase clinical trial, a substantial amount of safety information is already available. Earlier phases of clinical trials focus heavily on safety, so reaching this phase suggests that previous results have demonstrated it to be safe enough for more extensive testing. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for non-small cell lung cancer?

AZD9291 is unique because it targets a specific mutation in non-small cell lung cancer (NSCLC) called the T790M mutation in the EGFR gene. This mutation often causes resistance to first-generation EGFR inhibitors like gefitinib and erlotinib. While traditional treatments for NSCLC include chemotherapy and earlier EGFR inhibitors, AZD9291 (also known as osimertinib) is designed to overcome this resistance with improved precision. Researchers are excited about AZD9291 because it offers a more tailored approach, potentially leading to better outcomes and fewer side effects for patients with this specific mutation.

What evidence suggests that AZD9291 might be an effective treatment for non-small cell lung cancer?

Research has shown that AZD9291, also known as osimertinib, effectively treats non-small cell lung cancer, particularly when certain genetic changes are present. In this trial, some participants will receive AZD9291, which studies have shown helps patients live for nearly four years on average. One study found that after one year, 74% of patients taking osimertinib were alive and their cancer had not worsened, compared to only 22% of those on other treatments. Additionally, osimertinib has proven effective even at lower doses for patients who did not respond to initial treatments. These findings suggest that AZD9291 is a promising option for patients with specific lung cancer mutations, offering longer survival and better disease management. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Stage IB-IIIA non-small cell lung cancer that's been surgically removed. They must have specific EGFR mutations, no major organ issues, and can't be on certain drugs or have had certain treatments. Women must not be pregnant and use birth control.

Inclusion Criteria

My lung cancer is confirmed to be non-small cell and mostly not squamous.

I have had a brain MRI or CT scan before surgery.

My cancer was classified as Stage IB, II, or IIIA after surgery.

Exclusion Criteria

Treatment with an investigational drug within five half-lives of the compound or any of its related material

Your heart's electrical activity, called QT interval, is longer than normal.

I do not have severe illnesses, uncontrolled high blood pressure, active bleeding, or infections like hepatitis or HIV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AZD9291 or placebo daily following randomization

96 weeks

Regular visits for dosing and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Every 24 weeks until study completion or disease recurrence

Long-term follow-up

Participants are monitored for overall survival and disease-free survival

Up to 7 years

What Are the Treatments Tested in This Trial?

Interventions

• AZD9291
• Placebo AZD9291 80 mg/40 mg

Trial Overview The trial tests the effectiveness of AZD9291 (a targeted cancer drug) against a placebo in patients who've had surgery for lung cancer. Some may also receive standard chemotherapy. The goal is to see if AZD9291 improves outcomes post-surgery.

How Is the Trial Designed?

Group I: AZD9291 Experimental Treatment 2 Interventions

AZD9291 (80 mg or 40 mg orally, once daily), in accordance with the randomization schedule.

Group II: Placebo AZD9291 Placebo Group 1 Intervention

Matching placebo for AZD9291 (80 mg or 40 mg orally, once daily), in accordance with the randomization schedule.

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

AZD9291, an irreversible EGFR tyrosine kinase inhibitor, significantly enhances the effectiveness of radiation therapy in non-small cell lung cancer (NSCLC) cells with the EGFR T790M mutation, suggesting its potential as a radiation sensitizer.

The combination of AZD9291 and radiation not only increases cell death by delaying DNA repair and inducing apoptosis in resistant cancer cells but also shows improved tumor growth inhibition in animal models, indicating a promising avenue for future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AZD9291 Increases Sensitivity to Radiation in PC-9-IR Cells by Delaying DNA Damage Repair after Irradiation and Inducing Apoptosis. Wu, S., Zhu, L., Tu, L., et al.[2022]

Shikonin, a natural compound that induces reactive oxygen species (ROS), enhances the antitumor effects of AZD9291 in non-small cell lung cancer (NSCLC) cells with wild-type EGFR, suggesting a potential new treatment strategy.

The combination of shikonin and AZD9291 increases apoptosis in NSCLC cells through ROS-mediated endoplasmic reticulum (ER) stress, indicating that targeting ROS could improve outcomes for patients with wtEGFR NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A natural anthraquinone derivative shikonin synergizes with AZD9291 against wtEGFR NSCLC cells through reactive oxygen species-mediated endoplasmic reticulum stress. Hu, X., Zhang, ZY., Wu, LW., et al.[2022]

AZD9291, an EGFR-TKI used for treating non-small cell lung cancer, has a rare but serious side effect of inducing interstitial lung disease (ILD).

The case presented highlights the potential severity of ILD associated with AZD9291 treatment, emphasizing the need for awareness and monitoring in patients receiving this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fatal interstitial lung disease associated with AZD9291. Deng, SM., Huang, JA., Chen, YB.[2022]

ZD1839, an epidermal growth factor receptor (EGFR) inhibitor, has demonstrated effectiveness in treating advanced non-small cell lung cancer (NSCLC), showing improvements in symptoms and quality of life in two large phase II trials.

The ongoing research into ZD1839 and other EGFR inhibitors suggests they will play a significant role in NSCLC treatment, highlighting the need for healthcare professionals, especially nurses, to be informed about these emerging therapies for effective patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of clinical trials with epidermal growth factor receptor inhibitors in advanced non-small cell lung cancer. Thomas, M.[2019]

ZD 1839, a treatment for Non-Small-Cell Lung Cancer (NSCLC), has shown activity against brain metastases in four reported cases, indicating potential efficacy in this challenging area.

The response of brain metastases to ZD 1839 suggests that it may be a promising therapeutic option for patients with NSCLC who develop brain metastases, although further studies are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ZD 1839 in patients with brain metastases from non-small-cell lung cancer (NSCLC): report of four cases. Cappuzzo, F., Calandri, C., Bartolini, S., et al.[2023]

ZD1839, a targeted therapy that inhibits EGFR-associated tyrosine kinase activity, has shown efficacy in treating advanced non-small cell lung cancer (NSCLC) by disrupting tumor growth and survival mechanisms.

Clinical trials of ZD1839 not only assessed response rates but also focused on improving symptoms and quality of life for patients, highlighting its potential benefits beyond traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of epidermal growth factor receptor and symptom improvement in advanced non-small cell lung cancer. Natale, RB.[2005]

AZD2171, a potent inhibitor of vascular endothelial growth factor receptors, can be safely combined with standard chemotherapy (carboplatin and paclitaxel) in patients with advanced non-small-cell lung cancer, showing no dose-limiting toxicities at doses of 30 mg or 45 mg per day.

The combination treatment resulted in a 45% response rate, with tumor shrinkage observed in nearly all patients, indicating promising antitumor activity despite some manageable side effects like fatigue and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetic study of daily oral AZD2171, an inhibitor of vascular endothelial growth factor tyrosine kinases, in combination with carboplatin and paclitaxel in patients with advanced non-small-cell lung cancer: the National Cancer Institute of Canada clinical trials group. Laurie, SA., Gauthier, I., Arnold, A., et al.[2015]

In a study of 32 patients with non-small-cell lung cancer (NSCLC) treated with ZD1839 for over 90 days, the drug achieved a disease control rate of 56.25%, with 18.75% experiencing partial remission.

ZD1839 was associated with manageable side effects, including acneiform rash (31.25%) and diarrhea (18.75%), but notably did not cause interstitial lung disease, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical observation of ZD1839 in treating 32 cases of non-small-cell lung cancer]. Zhang, L.[2018]

AZD9291 is highly effective against non-small cell lung cancer (NSCLC) cells with the EGFR(L858R/T790M) mutation, significantly inhibiting cell growth and EGFR signaling pathways, while also causing apoptosis.

In vivo studies showed that oral administration of AZD9291 led to tumor regression in a mouse model, indicating its potential as a treatment for patients with T790 M-positive EGFR resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AZD9291 overcomes T790 M-mediated resistance through degradation of EGFR(L858R/T790M) in non-small cell lung cancer cells. Ku, BM., Bae, YH., Koh, J., et al.[2022]

Citations

1. 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 ...

2. 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.

3. 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 ...

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. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/New-study-results-reinforce-TAGRISSO-osimertinib-as-the-backbone-therapy-for-EGFR-mutated-lung-cancer-across-stages-and-settings.html

New study results reinforce TAGRISSO® (osimertinib) as ... Median OS was 58.8 months (95% CI 54.1, not calculable [NC]) in patients treated with TAGRISSO versus 54.1 months with placebo (95% CI 42.1, NC) ...

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

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38828959/

Phase II Efficacy and Safety of 80 mg Osimertinib in ... The study demonstrates significant intracranial efficacy and survival benefits of 80 mg once daily osimertinib in NSCLC patients with LMs.

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

Safety and efficacy of osimertinib plus consolidative ... Osimertinib plus consolidative SABR appears to provide a PFS and OS benefit when considered against historical data with osimertinib alone.

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1525730425001299

Osimertinib as First-Line Treatment for Patients With ... This study supports the long-term efficacy of OSI, with PFS and OS comparable to those in the FLAURA trial in a Japanese real-world setting.