Aurora A Kinase Inhibitor + Osimertinib for Non-Small Cell Lung Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Third-generation EGFR TKI

Must not be taking: Aurora kinase inhibitors

Disqualifiers: Brain metastases, Uncontrolled hypertension, others

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

Compensation: Varies

Number of Visits: 1

Duration: 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with a specific type of lung cancer that has spread. The study examines how well an aurora A kinase inhibitor, LY3295668, works with osimertinib to block enzymes that promote tumor growth. The goal is to determine the optimal dose and assess whether this combination can control the cancer. This trial suits those with advanced non-small cell lung cancer with specific EGFR mutations who have previously tried similar treatments and experienced cancer progression. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial group, offering participants a chance to contribute to groundbreaking cancer therapy advancements.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor to get specific guidance.

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

Research has shown that the aurora A kinase inhibitor LY3295668 is generally well-tolerated when used alone. The most common side effects included mouth sores and other mild to moderate issues, indicating that the drug does not cause severe problems for most people.

Osimertinib has been widely studied and is known for its safety. In previous studies, serious side effects occurred in about 22% of patients, indicating that most people did not experience severe issues. It has been used to treat certain types of lung cancer and maintains a good safety record.

Current trials are combining both treatments to assess their combined efficacy. While combining drugs can sometimes alter their effects, existing research provides a positive outlook on their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Aurora A Kinase Inhibitor LY3295668 and Osimertinib for non-small cell lung cancer because it targets cancer cells in a novel way. Unlike standard treatments that often focus solely on blocking the epidermal growth factor receptor (EGFR), this combination adds a new dimension by inhibiting Aurora A Kinase, an enzyme that plays a crucial role in cell division and tumor growth. This dual-target approach could potentially enhance the effectiveness of treatment by disrupting cancer cell proliferation more comprehensively, which might lead to better outcomes for patients who have limited options with current therapies.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research has shown that the drug combination of LY3295668 and osimertinib, which participants in this trial will receive, might help treat non-small cell lung cancer. In a study with these drugs, some patients prevented their cancer from worsening for six months, with 37% experiencing this benefit. LY3295668 stops cancer cells from dividing, leading to their death. Osimertinib is already known for extending the lives of lung cancer patients, with some studies showing survival of nearly four years in certain cases. Together, these drugs attack cancer cells in different ways, potentially controlling the disease more effectively. ^{1 2 3 4 5}

Who Is on the Research Team?

Xiuning Le, M.D., Ph.D.

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic non-squamous, EGFR-mutant non-small cell lung cancer who have progressed on osimertinib or similar treatments. They must be able to swallow pills, have measurable disease, and good organ function. Prior chemotherapy or immunotherapy is okay. Women of childbearing age and sexually active men must use contraception.

Inclusion Criteria

My lung cancer is advanced or has spread, and it's not the squamous type.

I am able to get out of my bed or chair and move around.

My NSCLC has a specific EGFR mutation.

Exclusion Criteria

I have been treated with aurora kinase inhibitors before.

I do not have any severe or uncontrolled illnesses.

My heart's electrical activity is normal and I don't have factors increasing my risk of irregular heartbeat.

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 and aurora A kinase inhibitor LY3295668 orally twice daily on days 1-28, repeated every 28 days for 24 cycles (2 years) in the absence of disease progression or unacceptable toxicity

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

30 days

1 visit (in-person) at 30 days, then every 4 months

What Are the Treatments Tested in This Trial?

Interventions

• Aurora A Kinase Inhibitor LY3295668
• Osimertinib

Trial Overview The trial tests the combination of LY3295668 (an aurora A kinase inhibitor) with osimertinib to see if they can better control tumor growth in patients by blocking enzymes needed for cell growth. It's a phase Ib/II study that also looks at side effects and the best dose.

How Is the Trial Designed?

Group I: Treatment (osimertinib, aurora A kinase inhibitor LY3295668) Experimental Treatment 2 Interventions

Patients receive osimertinib PO QD and aurora A kinase inhibitor LY3295668 PO BID on days 1-28. Treatment repeats every 28 days for 24 cycles (2 years) in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. esmoopen.com esmoopen.com/article/S2059-7029(24)00363-6/fulltext

16P A phase Ib/II trial to evaluate safety and efficacy of ... The RP2D was determined at LY3295668 25mg BID plus osimertinib 80mg daily. In the efficacy cohort (n=27), 6-month PFS rate was 37% (10/27). Three partial ...

2. aacrjournals.org aacrjournals.org/mct/article/18/12/2207/92720/Aurora-A-Selective-Inhibitor-LY3295668-Leads-to

Aurora A–Selective Inhibitor LY3295668 Leads to Dominant ... Aurora A–Selective Inhibitor LY3295668 Leads to Dominant Mitotic Arrest, Apoptosis in Cancer Cells, and Shows Potent Preclinical Antitumor Efficacy.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05017025

Aurora Kinase Inhibitor LY3295668 in Combination With ... Giving aurora A kinase inhibitor LY3295668 in combination with osimertinib may help control EGFR-mutant non-squamous non-small cell lung cancer. Detailed ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8345130/

Selective Inhibition of Aurora Kinase A by AK-01/LY3295668 ... In this study, we tested a promising drug based on genomic information from MCC patient tumors. We found that it was highly effective in killing MCC cells and ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0045206825005139

Aurora kinases, emerging critical targets for cancer ... Aurora kinase inhibitors (AKIs) were developed and tested in clinical trials and effectively suppressed many cancer types, suggesting the potential for Aurora ...