Osimertinib for Lung Cancer

Recruiting at 1 trial location

Overseen By Pasi A Jänne, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must be taking: Osimertinib

Must not be taking: CYP3A4 inhibitors/inducers

Disqualifiers: CNS disease, Heart disease, Infections, 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: 2

Duration: 6 months

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Osimertinib, a targeted therapy, to determine its effectiveness in treating Non-Small Cell Lung Cancer (NSCLC) with a specific gene change called an EGFR mutation. Participants take Osimertinib as a pill once a day. The trial seeks individuals with stage IV NSCLC and certain EGFR mutations identified in their tumor tissue. Those with lung cancer and these specific gene changes might be suitable for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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 take medications or supplements that strongly affect the enzyme CYP3A4. Check with the study team to see if your medications are on the list of those that need to be stopped.

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

Research has shown that osimertinib, also known as Tagrisso, is safe for treating non-small cell lung cancer (NSCLC) with an EGFR mutation. Over the past ten years, studies have found that most patients tolerate osimertinib well. While it can cause some side effects, these are usually manageable. This treatment has proven effective in various stages of lung cancer, helping patients live longer. As a result, osimertinib presents a promising option for those considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lung cancer?

Osimertinib is unique because it specifically targets a mutation in the EGFR gene, which is found in some non-small cell lung cancers. This precision makes it different from traditional chemotherapy, which attacks all rapidly dividing cells, often leading to more side effects. Researchers are excited about Osimertinib because it can penetrate the blood-brain barrier, offering potential protection against brain metastases, a common concern in lung cancer patients. Additionally, its oral administration makes it more convenient for patients compared to intravenous chemotherapy.

What evidence suggests that Osimertinib might be an effective treatment for Non-Small Cell Lung Cancer?

Research has shown that Osimertinib, the treatment under study in this trial, is highly effective for Non-Small Cell Lung Cancer (NSCLC) with an EGFR mutation. Studies have found that it significantly extends patients' lives. For those with advanced NSCLC, Osimertinib remains effective even when other treatments have failed. On average, patients taking Osimertinib live nearly four years. The treatment is generally well-tolerated, allowing patients to manage side effects more easily. This makes Osimertinib a promising option for individuals with this specific type of lung cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Pasi Jänne, MD, PhD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

Adults with stage IV Non-Small Cell Lung Cancer (NSCLC) and specific EGFR mutations can join this trial. They must have good organ function, not be pregnant or breastfeeding, use contraception, and agree to biopsies. Excluded are those who've had certain cancer treatments or uncontrolled brain metastases.

Inclusion Criteria

I am a male willing to use contraception during the trial and for 4 months after, and will not donate sperm during this time.

I have a tissue sample from my diagnosis available for testing, or I've already had NGS testing before starting osimertinib.

I am not pregnant or breastfeeding and agree to use contraception during and after the study.

Exclusion Criteria

I have not had any radiation therapy, including for the brain, in the last 2 weeks.

I do not have serious heart issues, lung disease, bleeding disorders, severe infections, or specific genetic mutations.

I have not been treated with EGFR or ERBB family targeted therapies, except possibly osimertinib in the first 3 months.

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 a day, dosage determined per protocol

6 months

CT scans every 2 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Clinic visits or phone calls

Post-progression Biopsy

Genomic changes evaluated using targeted next generation sequencing in the post-osimertinib tumor

4 months

What Are the Treatments Tested in This Trial?

Interventions

• Osimertinib

Trial Overview The trial is testing Osimertinib (Tagrisso), a targeted therapy for NSCLC with an EGFR mutation. Participants will take the drug and may have started treatment within three months before joining the study if they meet all criteria.

How Is the Trial Designed?

Group I: Osimertinib Experimental Treatment 1 Intervention

Osimertinib: Oral, once a day, dosage determined per protocol

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?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

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 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 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]

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]

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]

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. 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.

3. 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.

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

Osimertinib after Chemoradiotherapy in Stage III EGFR- ... Interim overall survival data (maturity, 20%) showed 36-month overall survival among 84% of patients with osimertinib (95% CI, 75 to 89) and 74% ...

5. jtocrr.org jtocrr.org/article/S2666-3643(24)00090-0/fulltext

The Whole Picture of First-Line Osimertinib for EGFR ... Results. A total of 583 patients received osimertinib. The median progression-free and overall survival were 20.0 (95% confidence interval [CI]: ...

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4940973/

The safety and efficacy of osimertinib for the ... - PubMed Central We review the rapid clinical development and approval of the third-generation EGFR TKI osimertinib for treatment of NSCLCs with EGFR-T790M.

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa1713137

Osimertinib in Untreated EGFR-Mutated Advanced Non– ... Osimertinib showed efficacy superior to that of standard EGFR-TKIs in the first-line treatment of EGFR mutation–positive advanced NSCLC.

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.