What side effects are associated with this type of intervention?

Common treatments for lung carcinoma, particularly those involving kinase inhibitors like Aurora A Kinase Inhibitor LY3295668 and EGFR inhibitors like Osimertinib, have several known side effects. Kinase inhibitors may cause fatigue, nausea, vomiting, diarrhea, and hematologic toxicities such as neutropenia. Osimertinib can lead to diarrhea, rash, dry skin, and nail toxicity, with severe side effects including interstitial lung disease, cardiomyopathy, and QT prolongation.

What prior FDA approvals exist?

For the treatment of lung carcinoma, several EGFR inhibitors have received FDA approval, including osimertinib, erlotinib, gefitinib, and afatinib. These drugs target the epidermal growth factor receptor (EGFR) and are used primarily in patients with EGFR-mutant non-small cell lung cancer (NSCLC). Additionally, other kinase inhibitors such as crizotinib, which targets ALK and ROS1, and dabrafenib in combination with trametinib, which targets BRAF V600E mutations, have also been approved for specific genetic profiles in lung cancer. These treatments are similar to the investigational combination of Aurora A Kinase Inhibitor LY3295668 and osimertinib, which aims to inhibit key enzymes involved in tumor growth.

What other types of research exist?

Promising novel alternatives for lung carcinoma patients include other EGFR inhibitors like afatinib and dacomitinib, which target EGFR mutations. Additionally, MET inhibitors (e.g., capmatinib, tepotinib) and RET inhibitors (e.g., selpercatinib, pralsetinib) are emerging as effective treatments for specific genetic alterations in lung cancer. Immunotherapy agents such as pembrolizumab and nivolumab, which target PD-1/PD-L1 pathways, also offer promising alternatives.

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Kinase Inhibitor

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

Phase 1 & 2

Waitlist Available

Led By Xiuning Le

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Histologically or cytologically confirmed non-squamous, non-small cell lung cancer locally advanced or metastatic disease.

Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

Must not have

Previous treatment with other aurora kinase inhibitors.

Any of the following cardiac criteria: Mean resting corrected QT interval (QTc using Fridericia's formula) > 470 msec, clinically important abnormalities in rhythm, conduction or morphology of resting ECG, factors that increase the risk of QTc prolongation or risk of arrhythmic events.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 30 days after last dose

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of two drugs, LY3295668 and osimertinib, in patients with advanced lung cancer that has a specific mutation and has spread. The drugs work by blocking enzymes and mutations that help cancer cells grow. Osimertinib is a third-generation treatment approved for advanced non-small cell lung cancer with specific mutations.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects include issues related to enzyme inhibition affecting cell growth which may lead to abnormal blood counts, digestive disturbances, fatigue, possible heart rhythm problems (QTc prolongation), and other common drug-related adverse events.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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

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My NSCLC has a specific EGFR mutation.

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I am 18 years old or older.

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I have a tumor larger than 10mm that hasn't been treated with radiation.

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I can swallow pills or capsules.

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I am a man who can father children and will use birth control.

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My blood, liver, and kidney tests are within normal ranges.

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I am not pregnant and agree to use birth control.

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I have been treated with a specific lung cancer medication and my cancer has progressed.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been treated with aurora kinase inhibitors before.

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

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I cannot take osimertinib due to severe nausea, vomiting, gut diseases, swallowing issues, or major bowel surgery.

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

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I am not using effective birth control, or I am pregnant or breastfeeding.

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My high blood pressure is not well-managed despite taking medication.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 30 days after last dose

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 30 days after last dose

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 30 days after last dose for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Dose-limiting toxicity and recommended phase 2 dose

Secondary study objectives

Best objective response rate

Progression-free survival

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (osimertinib, aurora A kinase inhibitor LY3295668)Experimental Treatment2 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Osimertinib

2017

Completed Phase 4

~1120

0 / 16Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Aurora A Kinase inhibitors, such as LY3295668, block the Aurora A Kinase enzyme, essential for cell division, thereby preventing tumor cell proliferation. Osimertinib inhibits the Epidermal Growth Factor Receptor (EGFR), which is often mutated in non-small cell lung cancer (NSCLC), disrupting the signaling pathways that promote tumor growth and survival. These targeted therapies are crucial for lung carcinoma patients as they aim to specifically disrupt cancer cell growth while minimizing damage to normal cells, potentially leading to more effective and less toxic treatment options.