Osimertinib + Gefitinib for Lung Cancer

Not currently recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: CYP3A4 inhibitors, Warfarin

Disqualifiers: CNS disease, Heart disease, Active infection, others

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

Compensation: Varies

Number of Visits: 2

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining two drugs, Osimertinib (Tagrisso) and Gefitinib (Iressa), as a treatment for Non-Small Cell Lung Cancer (NSCLC) in patients with a specific EGFR mutation. The researchers aim to determine if these medications together can improve outcomes for this type of lung cancer. It targets individuals with stage IV NSCLC who have not yet received targeted therapy, chemotherapy, or immunotherapy. Participants must have specific genetic markers identified in their cancer to qualify. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this combination therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications or herbal supplements that are known to strongly inhibit CYP3A4, as well as warfarin. You should avoid any medications or foods that induce CYP3A4. Check with the trial team for a full list of medications to avoid.

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

Research has shown that both osimertinib and gefitinib are generally well-tolerated treatments for non-small cell lung cancer (NSCLC) with an EGFR mutation. Many studies over the years have found that osimertinib has manageable side effects. In some studies, researchers considered the side effects of osimertinib acceptable.

Gefitinib is also regarded as a safe option for treating NSCLC compared to osimertinib. Both drugs are often used as first-choice treatments, meaning they are among the initial options doctors try for this type of cancer. This indicates that their safety is well-understood, which can reassure patients considering participation in a clinical trial with these medications.

While side effects can occur with any medication, evidence so far suggests that using these two drugs together is generally safe for most patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Osimertinib and Gefitinib for treating lung cancer because it targets the disease in a unique way. Most treatments for lung cancer, like chemotherapy, work by killing rapidly dividing cells, which can harm healthy cells too. However, Osimertinib and Gefitinib are both targeted therapies that specifically block the signals of cancer cell growth. Osimertinib targets a mutation in the epidermal growth factor receptor (EGFR) that is often resistant to standard drugs, while Gefitinib also inhibits EGFR but at a different point in the signaling pathway. This dual approach could lead to more effective treatment by overcoming resistance and potentially improving patient outcomes.

What evidence suggests that this trial's treatments could be effective for Non-Small Cell Lung Cancer?

Research has shown that both osimertinib and gefitinib effectively treat non-small cell lung cancer (NSCLC) with an EGFR mutation. Studies have found that osimertinib extends patients' lives and is generally well-tolerated. Gefitinib also proves effective as the initial treatment for patients with this mutation. In this trial, participants will receive a combination of these two drugs, which might enhance their effectiveness due to their complementary actions. While the combination remains under study, each drug alone has successfully treated this type of lung cancer. ^{2 3 4 5 6}

Who Is on the Research Team?

Pasi Janne

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

Adults over 18 with advanced Non-Small Cell Lung Cancer and specific EGFR mutations, who haven't had prior treatments for lung cancer or recent major surgery. They must not be pregnant, agree to use contraception, have a life expectancy over 12 weeks, and good organ function. Those with unstable health conditions or taking certain drugs are excluded.

Inclusion Criteria

You must have a disease that can be measured using specific criteria.

Participants must have a life expectancy of greater than 12 weeks

My stage IV lung cancer has a specific EGFR mutation.

Exclusion Criteria

I haven't taken any chemotherapy or experimental drugs for my advanced lung cancer.

I am not taking any strong CYP3A4 inhibitors.

I have been treated with drugs targeting EGFR or similar proteins.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive combination therapy with gefitinib and osimertinib, either concurrently or on an alternating schedule, for 6 cycles of 28 days each

24 weeks

Visits every 2 cycles for CT scans

Follow-up

Participants are monitored for overall survival and progression-free survival with clinic visits or phone calls

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Gefitinib
• Osimertinib

Trial Overview The trial is testing Osimertinib (Tagrisso) combined with Gefitinib (Iressa) as a treatment for NSCLC patients who have never received EGFR inhibitors before. It aims to see if this drug combo can effectively treat the cancer.

How Is the Trial Designed?

Group I: Gefitinib + Osimertinib Experimental Treatment 2 Interventions

* Gerfitinib will administered orally at a pre determine dose daily * Osimertinib will administered orally at a pre determine dose daily

Gefitinib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Iressa for:

• Non-small cell lung cancer (NSCLC)

Approved in United States as Iressa for:

• Non-small cell lung cancer (NSCLC)

Approved in Canada as Iressa for:

• Non-small cell lung cancer (NSCLC)

Approved in Japan as Iressa for:

• Non-small cell lung cancer (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 significantly improves progression-free survival (PFS) in patients with metastatic non-small cell lung cancer (NSCLC) with the EGFR T790M mutation, showing a median PFS of 10.1 months compared to 4.4 months with chemotherapy in a trial of 419 patients.

The safety profile of osimertinib is favorable compared to other EGFR tyrosine kinase inhibitors and chemotherapy, with common side effects including diarrhea and rash, making it a viable treatment option for patients who have progressed on previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Benefit-Risk Assessment of Osimertinib for the Treatment of Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor T790M Mutation. Odogwu, L., Mathieu, L., Goldberg, KB., 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]

In a study of 46 treatment-naive patients with EGFR-mutated advanced non-small cell lung cancer, alternating therapy with osimertinib and afatinib resulted in a median progression-free survival of 21.3 months, indicating promising efficacy despite not meeting the primary endpoint of 12-month progression-free survival probability.

The treatment was generally well-tolerated, with common side effects including diarrhea (73.9%) and rash (63.0%), and only a few cases of serious pneumonitis, suggesting a manageable safety profile for this alternating therapy approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternating therapy with osimertinib and afatinib for treatment-naive patients with EGFR-mutated advanced non-small cell lung cancer: A single-group, open-label phase 2 trial (WJOG10818L). Hayashi, H., Yonesaka, K., Nakamura, A., et al.[2022]

Osimertinib, an irreversible tyrosine kinase inhibitor, showed excellent activity in treating a 69-year-old man with metastatic EGFR-mutated non-small cell lung cancer, leading to a rapid treatment response despite initial severe pancytopenia.

After experiencing pancytopenia, the patient's dose of osimertinib was reduced from 80 mg to 40 mg daily, which allowed for continued effective treatment without further adverse events, demonstrating the potential for safe dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancytopenia During Osimertinib Treatment in a Patient with EGFR-Mutated Non-Small Cell Lung Cancer. Di Marino, P., Chiapperino, C., Primavera, FC., et al.[2022]

Osimertinib is a third-generation EGFR tyrosine kinase inhibitor specifically designed to target the EGFR T790M mutation, which is a common cause of resistance to first-line EGFR TKIs in advanced non-small-cell lung cancer.

This review highlights the efficacy of osimertinib in clinical trials, demonstrating its ability to effectively treat patients with non-small-cell lung cancer harboring the T790M mutation while minimizing effects on normal EGFR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib making a breakthrough in lung cancer targeted therapy. Zhang, H.[2020]

Osimertinib (AZD9291) is effective in prolonging survival for non-small cell lung cancer patients with EGFR mutations, but resistance to the drug is a common issue, prompting the need to explore resistance mechanisms.

In this study, AZD9291-resistant NSCLC cell lines were established, revealing significant changes in circular RNA (circRNA) expression profiles, which may contribute to drug resistance and could serve as potential targets for future gene therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive analysis of circular RNA profiling in AZD9291-resistant non-small cell lung cancer cell lines. Chen, T., Luo, J., Gu, Y., et al.[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, a third-generation EGFR tyrosine kinase inhibitor, effectively inhibited the growth of a brain metastasis in a patient with lung adenocarcinoma that was resistant to both radiotherapy and surgery.

The case highlights the importance of re-biopsy in patients with EGFR-mutated non-small cell lung cancer who develop resistance to TKI treatments, as it can provide critical information for effective treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid Intracranial Response to Osimertinib in a Patient with Epidermal Growth Factor Receptor T790M-Positive Adenocarcinoma of the Lung. Reichegger, H., Jochum, W., Förbs, D., 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 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. clinicaltrials.gov clinicaltrials.gov/study/NCT02296125

NCT02296125 | AZD9291 Versus Gefitinib or Erlotinib in ... This is a Phase III, double-blind, randomised study assessing the efficacy and safety of AZD9291 (80 mg orally, once daily) versus a standard of care (SoC) ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39257317/

Efficacy and Safety of Osimertinib, Erlotinib, and Gefitinib ... The pooled analyses have shown that erlotinib, gefitinib, and osimertinib are safe and effective first-line treatment options for patients ...

3. 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 ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2212534524001497

Comparison of efficacy of gefitinib and osimertinib for ... Comparison of efficacy of gefitinib and osimertinib for untreated EGFR mutation-positive non-small-cell lung cancer in patients with poor performance status.

5. 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 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7049494/

New data highlighting the efficacy and safety outcomes ... Osimertinib was effective in the treatment of NSCLC patients with rare EGFR mutations and that the toxicities caused by the treatment were acceptable.