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

Description

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.