Osimertinib for Non-Small Cell Lung Cancer

Recruiting at 377 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inducers, St John's wort

Disqualifiers: Interstitial lung disease, Brain metastases, Heart failure, others

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

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: 3

Duration: 21 days per cycle, ongoing until disease progression or unacceptable toxicity

46 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of osimertinib for certain types of advanced non-small cell lung cancer (NSCLC). It targets patients whose cancer has a specific gene change (EGFR exon 20 insertion mutation) and is either advanced or has recurred after previous treatment. Osimertinib may help by blocking enzymes that cancer cells need to grow. Suitable candidates have NSCLC with the mentioned mutation and have previously received cancer treatment. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for the trial?

The trial does not specify that you must stop all current medications, but you cannot take medications or supplements that strongly affect CYP3A4 enzymes. If you are on such medications, you need to stop them at least 3 weeks before starting the trial. It's best to discuss your current medications with the trial team to ensure they are safe to continue.

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

Research has shown that osimertinib is generally well-tolerated by patients with non-small cell lung cancer. Studies have demonstrated that it offers significant survival benefits and has a manageable safety profile. One study found that taking 80 mg of osimertinib daily was effective, even for patients whose cancer had spread to the brain.

While some side effects might occur, they are usually manageable. The FDA has already approved osimertinib for other uses, which adds to the confidence in its safety.

Overall, evidence suggests that osimertinib is a promising treatment option for patients, with a history of being well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Osimertinib is unique because it specifically targets a mutation in the EGFR gene, which is responsible for the growth of cancer cells in many non-small cell lung cancer (NSCLC) patients. Unlike traditional chemotherapy, which attacks rapidly dividing cells indiscriminately, osimertinib is a targeted therapy that hones in on these mutated cells, potentially reducing damage to healthy cells and improving patient outcomes. Researchers are excited about osimertinib because it has shown the ability to penetrate the central nervous system, offering hope for treating brain metastases in NSCLC patients, a challenge for many existing treatments.

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

Research shows that osimertinib, the treatment under study in this trial, effectively treats non-small cell lung cancer (NSCLC) when certain genetic changes are present. Studies have found that osimertinib helps patients live longer and is generally well-tolerated by those with advanced NSCLC. Specifically, patients with changes in the EGFR gene who took osimertinib after other treatments failed experienced positive outcomes. This treatment blocks proteins that aid cancer cell growth, potentially slowing or stopping the cancer. Overall, osimertinib has shown promising results for patients with specific genetic types of NSCLC. ^{4 6 7 8 9}

Who Is on the Research Team?

Zofia Piotrowska

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

Adults with stage IIIB-IV or recurrent non-small cell lung cancer and a specific mutation (EGFR exon 20 insertion) can join this trial. They must have had prior therapy, no other active cancers, controlled heart conditions, and not be on certain medications that affect the drug being tested. Pregnant or breastfeeding women are excluded, as well as those with symptomatic brain metastases.

Inclusion Criteria

I am not taking, nor can stop taking, strong CYP3A4 inducers 3 weeks before the study.

I have had at least one treatment for my advanced lung cancer.

Your kidney function is within the normal range based on recent tests.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive osimertinib orally once daily on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

21 days per cycle, ongoing until disease progression or unacceptable toxicity

Regular visits for ECHO or MUGA, MRI or CT with contrast, and blood sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and every 3 months for up to 5 years.

Up to 5 years

Follow-up visits every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Osimertinib

Trial Overview The trial is testing Osimertinib's effectiveness in treating advanced lung cancer with a particular genetic change. It involves collecting biological samples and using imaging tests like CT scans and MRIs to monitor the tumor's response to treatment.

How Is the Trial Designed?

Group I: Treatment (osimertinib) Experimental Treatment 6 Interventions

Patients receive osimertinib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA, MRI or CT with contrast, and collection of blood samples throughout the trial.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

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]

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 (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 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]

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]

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 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]

Citations

1. 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.

2. 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.

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

Cost‐Effectiveness of Osimertinib in Treating Newly ... The objective of this study was to assess cost and effectiveness of osimertinib in treating newly diagnosed advanced non‐small cell lung cancer with an ...

4. astrazeneca.com astrazeneca.com/content/astraz/media-centre/press-releases/2025/tagrisso-plus-chemotherapy-demonstrated-a-median-overall-survival-of-nearly-four-years.html

Tagrisso plus chemotherapy demonstrated a median ... Over the past decade, Tagrisso has consistently delivered strong survival benefits and tolerable safety across all stages of non-small cell lung ...

5. 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.

6. 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.

7. 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 ...

8. 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 ...

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

Osimertinib with or without Chemotherapy in EGFR- ... CNS efficacy of osimertinib in patients with T790M-positive advanced non-small-cell lung cancer: data from a randomized phase III trial (AURA3).