Osimertinib for Early-Stage Non-Small Cell Lung Cancer

Not currently recruiting at 3 trial locations

Overseen By Lisa Tan

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, San Francisco

Must be taking: EGFR inhibitors

Must not be taking: QTc prolonging, CYP3A4 inducers

Disqualifiers: CNS metastases, Interstitial lung disease, HIV, Active second malignancy, 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: 30

Duration: 4-8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of osimertinib for individuals with a specific type of early-stage lung cancer, known as non-small cell lung cancer, before surgery. Osimertinib blocks signals that promote the growth of mutant cancer cells. The trial targets those with a particular mutation who plan to have their tumors surgically removed. Suitable candidates have a confirmed diagnosis of this lung cancer type and are eligible for surgery. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in cancer treatment.

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

The trial requires that you avoid certain medications that prolong the QT interval or are potent CYP3A4 inducers. If you are on these medications, you may need to stop or switch them before starting the trial. It's best to discuss your current medications with the trial team to see if any changes are needed.

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

Research shows that osimertinib is a promising and well-tolerated treatment for early-stage non-small cell lung cancer with specific genetic changes called EGFR mutations. Studies have consistently found that osimertinib extends patients' lives and has a safety profile that most can handle. Most patients can take the treatment without severe side effects. While some side effects might occur, they are usually manageable and not serious enough to outweigh the treatment's potential benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for early-stage non-small cell lung cancer, which often include surgery, chemotherapy, and radiation, osimertinib offers a targeted approach. Osimertinib is unique because it specifically targets and inhibits the epidermal growth factor receptor (EGFR) mutation, which is a common driver in some types of lung cancer. This precision targeting means it can potentially be more effective and have fewer side effects compared to traditional chemotherapy. Researchers are particularly excited about osimertinib because it has shown promise in shrinking tumors quickly before surgery, potentially improving surgical outcomes and sparing patients from more aggressive treatments.

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

Research shows that osimertinib, which participants in this trial will receive, is a promising treatment for early-stage non-small cell lung cancer (NSCLC) with specific genetic changes called EGFR mutations. Studies have found that osimertinib can greatly improve survival rates in patients whose cancer has been surgically removed and is in stages IB to IIIA. The treatment also reduces the chance of cancer returning after surgery. Additionally, osimertinib is generally well-tolerated, meaning it usually doesn't cause severe side effects for most people. This makes it an appealing option for managing cancer effectively. ^{1 2 3 4 6}

Who Is on the Research Team?

Collin Blakely, MD, PhD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

Adults over 18 with stage I-IIIA non-small cell lung cancer that has a specific EGFR mutation. They must be fit for surgery, have an ECOG Performance Status of 0-1, and meet certain blood test criteria. Excluded are those with advanced cancer stages, active second cancers, certain heart conditions, uncontrolled diseases or infections, pregnancy or breastfeeding women.

Inclusion Criteria

I don't have severe side effects from previous treatments.

My hemoglobin is at least 9 g/dL and I haven't had a blood transfusion in the last 28 days.

My kidney function is good, with a filtration rate over 50 mL/min.

Exclusion Criteria

I have another cancer, but it's completely treated.

Participation in another clinical study with an investigational product during the last 2 months or within five half-lives of the compound

Involvement in the planning and/or conduct of the study

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 for 28 days per cycle, up to 2 cycles, before surgery

4-8 weeks

Daily oral administration

Surgery

Participants undergo surgical resection of their cancer

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Follow-up at 30 days, then every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Osimertinib
• Therapeutic Conventional Surgery

Trial Overview The trial is testing the effectiveness of Osimertinib before surgery in patients with early-stage lung cancer that has a particular genetic change (EGFR mutation). The goal is to see if this drug can halt tumor growth by blocking the mutant proteins.

How Is the Trial Designed?

Group I: Treatment (osimertinib) Experimental Treatment 2 Interventions

Participants receive 80mg osimertinib orally, once a day (PO QD) on days 1-28. Treatment repeats every 28 days for a minimum of 1 cycle prior to surgery in the absence of disease progression or unacceptable toxicity. Investigators will have the option to give a second cycle of study drug prior to surgery if clinically indicated. Depending on the timing of the final scans, patients may ultimately receive up to two weeks additional therapy with study drug beyond end of cycle 1 (or cycle 2) while awaiting surgery. Patients then undergo surgical resection of their cancer. No treatment with the study drug will be given after surgery.

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?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

AstraZeneca

Industry 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]

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]

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]

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 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 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]

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]

Citations

1. 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 ...

2. 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 ...

3. 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.

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2304594

Overall Survival with Osimertinib in Resected EGFR ... Adjuvant osimertinib provided a significant overall survival benefit among patients with completely resected, EGFR-mutated, stage IB to IIIA NSCLC.

5. 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 ...

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

Osimertinib plus consolidative radiotherapy for advanced ... To the best of our knowledge, this is the first study to evaluate the efficacy and tolerability of consolidation radiation therapy (RT) ...