Osimertinib + Selumetinib for Lung Cancer

Recruiting at 3 trial locations

Overseen By Pasi A Janne, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: CYP3A4 inhibitors, Vitamin E

Disqualifiers: Heart disease, CNS disease, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 2 years

25 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study is studying a combination of two targeted therapies as a possible treatment for Non-Small Cell Lung Cancer (NSCLC) with an EGFR mutation. The drugs involved in this study are: * Osimertinib (Tagrisso) * Selumetinib

Will I have to stop taking my current medications?

The trial requires that you stop taking medications that are potent inhibitors or inducers of CYP3A4, as well as high doses of supplemental vitamin E. If you are on these medications, you will need to follow specific washout times before participating.

What data supports the effectiveness of the drug combination Osimertinib and Selumetinib for lung cancer?

Osimertinib has shown effectiveness in treating non-small cell lung cancer (NSCLC) with specific mutations, improving disease-free survival and being well-tolerated. It targets mutations that often cause resistance to other treatments, making it a promising option for certain lung cancer patients. ^{1 2 3 4 5}

Is the combination of Osimertinib and Selumetinib safe for humans?

Osimertinib has been generally well tolerated in clinical trials for lung cancer, with common side effects including diarrhea, rash, dry skin, and nail issues. Serious side effects were less common, and the safety profile was considered manageable. ^{2 4 6 7 8}

How is the drug combination of Osimertinib and Selumetinib unique for lung cancer treatment?

The combination of Osimertinib and Selumetinib is unique because it targets specific mutations in lung cancer cells, with Osimertinib focusing on the EGFR mutation and Selumetinib inhibiting MEK1/2, potentially overcoming resistance to other treatments. This approach aims to improve effectiveness by addressing multiple pathways that cancer cells use to grow. ^{1 2 4 5 9}

Research Team

Pasi Janne

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for adults with stage IV Non-Small Cell Lung Cancer (NSCLC) who have specific EGFR mutations and are new to treatment. They must be in good physical condition, not pregnant or breastfeeding, willing to use contraception, and have no history of severe allergic reactions to similar drugs. Prior cancer treatments should not include EGFR-targeted therapy or chemotherapy for metastatic disease.

Inclusion Criteria

I have a tissue sample from my diagnosis available for advanced genetic testing.

I am not pregnant or breastfeeding and have confirmed this with a test or meet criteria proving I cannot become pregnant.

I am willing to use contraception or abstain from sex during and for 3 months after treatment.

Exclusion Criteria

I am allergic to medications similar to osimertinib or selumetinib.

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

I haven't had any cancer except for certain skin cancers or cervical cancer in situ in the last 3 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Osimertinib daily and Selumetinib intermittently (4 days on, 3 days off) to assess safety and effectiveness

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Clinic visits or phone calls

Treatment Details

Interventions

• Osimertinib
• Selumetinib

Trial Overview The study tests a combination of Osimertinib (Tagrisso) and Selumetinib as potential treatments for NSCLC with an EGFR mutation. It aims to see how well these two targeted therapies work together compared to current standard care.

Participant Groups

Group I: Osimertinib + Selumetinib Experimental Treatment 2 Interventions

* Selumetinib are to be administered orally intermittently (4 days on, 3 days off) * Osimertinib are to be administered orally on a daily basis

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+

National Comprehensive Cancer Network

Collaborator

Trials

121

Recruited

7,400+

Findings from Research

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 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, a treatment for metastatic EGFRm T790M non-small-cell lung cancer, has been analyzed using newly developed and validated LC-MC/MS methods across various biological matrices, including plasma, urine, and cerebrospinal fluid.

The assays demonstrated high selectivity, accuracy, and robustness, successfully analyzing over 20,000 clinical samples, which supports the effective clinical development of osimertinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of osimertinib in human plasma, urine and cerebrospinal fluid. Mitchell, R., Bailey, C., Ewles, M., 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, 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 (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 an approved adjuvant treatment for non-small cell lung cancer patients with specific tumor mutations, highlighting its targeted therapeutic approach.

Common side effects of osimertinib include blood-related issues like leukopenia and thrombocytopenia, as well as gastrointestinal and skin reactions, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Adjuvant Drug for Lung Cancer. Aschenbrenner, DS.[2023]

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]

The combination of osimertinib with selumetinib or savolitinib showed a promising objective response rate of around 42-44% in patients with advanced EGFR-mutant non-small-cell lung cancer, indicating potential efficacy of these combinations.

However, combining osimertinib with durvalumab was not feasible due to a higher incidence of interstitial lung disease, highlighting safety concerns with this particular combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TATTON: a multi-arm, phase Ib trial of osimertinib combined with selumetinib, savolitinib, or durvalumab in EGFR-mutant lung cancer. Oxnard, GR., Yang, JC., Yu, H., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Effectiveness of osimertinib in patients with lung adenocarcinoma in clinical practice - the Expanded Drug Access Program in Poland. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Osimertinib: First Global Approval. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Determination of osimertinib in human plasma, urine and cerebrospinal fluid. [2022]

4. France pubmed.ncbi.nlm.nih.gov

Osimertinib: A Review in Completely Resected, Early-Stage, EGFR Mutation-Positive NSCLC. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Pancytopenia During Osimertinib Treatment in a Patient with EGFR-Mutated Non-Small Cell Lung Cancer. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Osimertinib for the Treatment of Metastatic EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

New Adjuvant Drug for Lung Cancer. [2023]

8. England 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. [2022]

9. England pubmed.ncbi.nlm.nih.gov

TATTON: a multi-arm, phase Ib trial of osimertinib combined with selumetinib, savolitinib, or durvalumab in EGFR-mutant lung cancer. [2022]