LY3295668

P1, N=71, Active, not recruiting, Eli Lilly and Company | Trial completion date: Aug 2025 --> Aug 2026

P1/2, N=32, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Jun 2025 --> Jun 2026

LY3295668 erbumine had a manageable safety profile as monotherapy and in combination therapy. Although proof-of-concept clinical responses were observed, future studies with biomarker-selected populations and/or novel combinations may yield higher response rates with Aurora kinase A inhibition.

P1, N=71, Active, not recruiting, Eli Lilly and Company | Trial completion date: Aug 2024 --> Aug 2025

It also evaluated the efficacy of the ABL TKI asciminib and the aurora kinase inhibitor LY3295668. Combining asciminib and aurora kinase inhibition enhanced the efficacy and is proposed as a new therapeutic option for patients with CML. These findings have clinical implications for a potential novel therapeutic strategy for CML patients.

P1, N=10, Active, not recruiting, Melbourne Health | Recruiting --> Active, not recruiting

P1/2, N=32, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

P2, N=95, Recruiting, AnHeart Therapeutics Inc. | Not yet recruiting --> Recruiting | Trial completion date: Feb 2027 --> Jul 2027 | Trial primary completion date: Jan 2026 --> Mar 2027

JHH6 cells, an undifferentiated HCC-derived in vitro model, were treated for 72 hours with two inhibitors of the kinase activity of AURKA (Alisertib and AK-01) and short interfering RNA (siRNA) targeting AURKA. AURKA is positively correlated with PD-L1 in both HCC and non-tumor tissues. The inhibition of kinase activity of AURKA enhances the number of polynucleated cells due to defects in chromosome separation and incorrect mitosis. The reduced expression of PD-L1 following AURKA inhibition highlights the potentiality of AURKA inhibitors in cancer therapy, possibly in combination with new immune checkpoint inhibitors.

P1a/1b, N=400, Recruiting, Eli Lilly and Company | Trial completion date: Nov 2023 --> Sep 2025 | Trial primary completion date: Nov 2023 --> Sep 2025

This study aims to evaluate the effects of two different AURKA inhibitors (Alisertib and AK-01) in liver cancer, focusing on the role of AURKA in the regulation of Programmed deathligand 1 (PD-L1) expression. This study underlines the relevance of AURKA as a key player in liver cancer thus suggesting possible future applications of AURKA inhibitors as therapy for liver cancer. In this regard, the link with PD-L1 may suggest a feasible strategy consisting of the use of AURKA inhibitors in combination with PD-1/PD-L1 inhibitors.

Key objectives of Phase 1b are to determine the safety and tolerability of LY3537982 monotherapy, and in combination with various agents: abemaciclib, erlotinib, cetuximab, an investigational ERK inhibitor (LY3214996), an investigational Aurora A kinase inhibitor (LY3295668), and an anti-PD1 antibody. Key exclusion criteria include presence of serious cardiac conditions, interstitial lung disease, symptomatic CNS malignancy, symptomatic CNS metastasis, or carcinomatous meningitis. The trial is currently enrolling patients (NCT04956640).