NCT05017025

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

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 32 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed 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.

Conditions

• Advanced Lung Non-Squamous Non-Small Cell Carcinoma
• Metastatic Lung Non-Squamous Non-Small Cell Carcinoma
• Stage III Lung Cancer AJCC v8
• Stage IIIA Lung Cancer AJCC v8
• Stage IIIB Lung Cancer AJCC v8
• Stage IIIC Lung Cancer AJCC v8
• Stage IV Lung Cancer AJCC v8
• Stage IVA Lung Cancer AJCC v8
• Stage IVB Lung Cancer AJCC v8

Interventions

Type	Name	Description
DRUG	Aurora A Kinase Inhibitor LY3295668	Given PO
DRUG	Osimertinib	Given PO

Timeline

• Start date: 2022-02-17
• Primary completion: 2026-06-30
• Completion: 2026-06-30
• First posted: 2021-08-23
• Last updated: 2025-11-19

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study