Abstract CT083: A Phase I/II study of aurora kinase A inhibitor, LY3295668 erbumine (AK-01): Safety as monotherapy in patients with locally advanced or metastatic solid tumors
Authors: Chu Quincy , Bouganim Nathaniel , Fortier Caroline , Zaknoen Sara , Stille John R. , Kremer Jill D. , Yuen Eunice , Hui Yu-Hua , Peña Amparo de la , Lithio Andrew , Smith Patricia S. , Batist Gerald 
Published: August 2019

Abstract
Background: LY3295668 erbumine (AK-01) is a selective, reversible, ATP-competitive small molecule inhibitor of aurora kinase A (AurA). LY3295668 erbumine treatment in xenograft and patient-derived xenograft models resulted in tumor growth arrest or regression of several tumor types with an acceptable safety profile. This study evaluated dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and safety of LY3295668 erbumine monotherapy in patients with locally advanced or metastatic solid tumors.
Methods: This ongoing phase I/II, open-label, multicenter study enrolled patients with locally advanced or metastatic solid tumors, ECOG PS 0-1, estimated life expectancy ≥ 12 weeks, adequate organ function, disease progression after 1 - 4 regimens for locally advanced or metastatic disease and no history of clinically significant cardiac disease. The primary objective was to determine MTD; secondary objectives included evaluation of tolerability and overall safety profile of LY3295668 erbumine. All patients received oral, twice daily (BID) doses of LY3295668 erbumine in cycles of 21 days in a multiple ascending dose schedule. Adverse events (AEs) were graded per NCI CTCAE v4.03.
Results: Twelve patients median age of 60 (range 39-74, 5 male and 7 female) were enrolled in the phase I study at the following dose levels: 25 mg (n=8); 50 mg (n=2); 75 mg (n=2). One patient in the 25 mg cohort experienced a DLT of grade (G) 3 mucositis. One patient in the 50 mg cohort experienced a DLT of G3 mucositis and G3 diarrhea. Both patients in the 75 mg cohort experienced DLTs (1=G3 mucositis, 1=G4 mucositis and G3 corneal deposits). The treatment-related AEs (TRAEs) observed in each cohort were as follows: in the 25 mg treatment group, six patients experienced various G1/2 TRAEs with only mucositis reported in &gt; one patient (n=2); G3 TRAEs were anemia (n=1) and mucositis (n=1). In the two patients receiving 50 mg, G3 TRAEs were: mucositis (n=1), diarrhea (n=1), and upper chest rash (n=1). In the two patients receiving 75 mg, G3/4 TRAEs were: mucositis (n=2), corneal deposits (n=1), neutropenia (n=1) and diarrhea (n=1). There were no treatment-related deaths. During this study, three patients died due to disease progression: one patient died &lt; 30 days and two patients died &gt; 30 days after the last treatment dose. At the time of data lock, two of the eight patients in the 25 mg BID phase I cohort remained on treatment for ≥ 8 months. In addition to the 12 patients in phase I, one patient was enrolled in phase II after the MTD was determined, totaling 13 patients who received treatment in the entire study.
Conclusion: The MTD of LY3295668 erbumine was determined to be 25 mg BID and found to be well tolerated in patients with locally advanced or metastatic solid tumors.
Trial Registration: NCT03092934
Citation Format: Quincy Chu, Nathaniel Bouganim, Caroline Fortier, Sara Zaknoen, John R. Stille, Jill D. Kremer, Eunice Yuen, Yu-Hua Hui, Amparo de la Peña, Andrew Lithio, Patricia S. Smith, Gerald Batist. A Phase I/II study of aurora kinase A inhibitor, LY3295668 erbumine (AK-01): Safety as monotherapy in patients with locally advanced or metastatic solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT083.