A phase 1 study of AMG 900, an orally administered pan‐aurora kinase inhibitor, in adult patients with acute myeloid leukemia. Issue 7 (5th June 2017)

• Record Type: Journal Article
• Authors: Kantarjian, Hagop M.; Schuster, Michael W.; Jain, Nitin; Advani, Anjali; Jabbour, Elias; Gamelin, Erick; Rasmussen, Erik; Juan, Gloria; Anderson, Abraham; Chow, Vincent F.; Friberg, Gregory; Vogl, Florian D.; Sekeres, Mikkael A.
• Is Part Of: American journal of hematology. Volume 92:Issue 7(2017:Jul.)
• Page Start: 660
• Page End: 667
• Publication Date: 2017-06-05
• Subjects: Hematology -- Periodicals; 616.15
• DOI: 10.1002/ajh.24736
• Languages: English
• ISSNs: 0361-8609

Abstract

Abstract: Aurora kinases are involved in the pathophysiology of several cancers including acute myeloid leukemia (AML). In this phase 1 study, we investigated the safety and efficacy of AMG 900, an orally administered, highly potent, selective, small‐molecule inhibitor of both Aurora kinase A and B, in patients with AML . Patients with pathologically documented AML who either declined standard treatments or had relapsed from or were refractory to previous therapies were enrolled. Two every‐2‐week dose‐escalation schedules using a modified 3 + 3 + 3 design were evaluated AMG 900 given daily for 4 days with 10 days off (4/10 schedule), and AMG 900 given daily for 7 days with 7 days off (7/7 schedule). Thirty‐five patients were enrolled at 9 different dose levels: 22 patients on the 4/10 schedule (doses from 15 to 100 mg daily), and 13 patients on the 7/7 schedule (doses from 30 to 50 mg daily). Both schedules were tolerated; nausea (31%), diarrhea (29%), febrile neutropenia (29%), and fatigue (23%) were the most common treatment‐related adverse events. Three patients (9%) achieved complete response with incomplete count recovery. Patients with higher baseline expression of a set of specific pathway‐related genes ( BIRC5, AURKA, TTK, CDC2, and CCNB1 ) were more likely to respond in an exploratory biomarker analysis. AMG 900 was tolerated in a general AML population, and pathway‐specific biomarkers identified a potential target population. Future research efforts will be directed toward further exploration of biomarkers of response and combination of AMG 900 with other anticancer agents.