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Osimertinib

Tyrosine Kinase Inhibitors

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Tyrosine

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.

Aurora A Kinase Inhibitor LY3295668

Xiuning Le

This phase Ib/II trial studies the side effects and best dose of aurora A kinase inhibitor LY3295668 when given together with osimertinib in patients with EGFR-mutant non-squamous non-small cell lung cancer that has spread to other places in the body (advanced or metastatic). Aurora A kinase inhibitor LY3295668 and osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving aurora A kinase inhibitor LY3295668 in combination with osimertinib may help control EGFR-mutant non-squamous non-small cell lung cancer.

PRIMARY OBJECTIVES:

I. To evaluate dose-limiting toxicity (DLT) and to establish the recommended phase II dose (RP2D) of aurora A kinase inhibitor LY3295668 (LY3295668) given in combination with osimertinib in patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC).

II. To preliminarily assess efficacy of LY3295668 plus osimertinib in advanced EGFR-mutant NSCLC who progressed on prior EGFR tyrosine kinase inhibitor (TKI). The co-primary endpoints are progression-free survival (PFS) at 6 months after treatment and best objective response rate (BRR) within 6 months after treatment.

SECONDARY OBJECTIVES:

I. Determine the objective response rate (ORR) with osimertinib LY3295668 combination.

II. Determine the overall survival (OS) with osimertinib LY3295668 combination. III. Determine the disease control rate (DCR) with osimertinib LY3295668 combination.

IV. Determine the safety and tolerability with osimertinib LY3295668 combination.

CORRELATIVE/EXPLORATORY OBJECTIVES:

I. Explore the association of baseline genomic profiles (from tumor, germline deoxyribonucleic acid \[DNA\], and circulating tumor \[ct\]DNA) with clinical benefit in patients treated with osimertinib LY3295668 combination.

II. Explore resistance mechanisms to osimertinib LY3295668 combination. III. Determine the immunomodulatory effects of osimertinib LY3295668 combination.

OUTLINE:

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

After completion of study treatment, patients are followed up at 30 days and then every 4 months thereafter.

Aurora Kinase Inhibitor LY3295668 in Combination With Osimertinib for the Treatment of Advanced or Metastatic EGFR-Mutant Non-squamous Non-small Cell Lung Cancer

A Phase Ib/II Trial to Evaluate Safety, Tolerability and Efficacy of Aurora Kinase Inhibitor LY3295668 in Combination With Osimertinib for Patients With EGFR-Mutant Non-Small Cell Lung Cancer

Adverse event data will be summarized by type and severity grade.

Will be estimated using the method of Kaplan and Meier. Will be provided with 95% confidence intervals.

Will be provided with 95% confidence intervals.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for aurora a kinase inhibitor ly3295668