Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/126763
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Type: Journal article
Title: A phase 1, first-in-human study of AMG 900, an orally administered pan-Aurora kinase inhibitor, in adult patients with advanced solid tumors
Author: Carducci, M.
Shaheen, M.
Markman, B.
Hurvitz, S.
Mahadevan, D.
Kotasek, D.
Goodman, O.
Rasmussen, E.
Chow, V.
Juan, G.
Friberg, G.
Gamelin, E.
Vogl, F.
Desai, J.
Citation: Investigational New Drugs, 2018; 36(6):1060-1071
Publisher: Springer
Issue Date: 2018
ISSN: 0167-6997
1573-0646
Statement of
Responsibility: 
Michael Carducci, Montaser Shaheen, Ben Markman, Sara Hurvitz, Daruka Mahadevan, Dusan Kotasek ... et al.
Abstract: Background Aurora kinase overexpression or amplifications are associated with high proliferation, poor prognosis, and therapeutic resistance in human tumors. AMG 900 is an investigational, oral, selective pan-Aurora kinase inhibitor. Methods This first-in-human trial included dose-escalation and dose-expansion phases ( ClinicalTrials.gov : NCT00858377). Dose escalation evaluated the safety, tolerability, and pharmacokinetics of AMG 900 in advanced solid tumors and determined the maximum tolerated dose (MTD) with/without granulocyte colony-stimulating factor (G-CSF) prophylaxis. Dose expansion evaluated clinical activity in three tumor types: taxane- and platinum-resistant ovarian cancer, taxane-resistant triple-negative breast cancer (TNBC), and castration-resistant and taxane- or cisplatin/etoposide-resistant prostate cancer (CRPC). AMG 900 was administered 4 days on/10 days off at 1-50 mg/day during escalation and at the MTD with G-CSF during expansion. Results AMG 900 showed rapid absorption with fast clearance, supporting once-daily dosing. The MTD was 25 mg/day, increasing to 40 mg/day with G-CSF. Grade ≥ 3 treatment-related adverse events included neutropenia (37%), anemia (23%), leukopenia (14%), and thrombocytopenia (12%). During dose expansion, 3/29 (10.3%, 95% CI: 2.0%-28.0%) evaluable patients with ovarian cancer experienced partial response by central imaging per RECIST 1.1; median duration of response was 24.1 weeks (95% CI: 16.1-34.1). Seven patients (24.1%, 95% CI: 10.3%-43.5%) experienced partial response per Gynecologic Cancer InterGroup criteria; 5/9 patients positive for p53 expression responded to treatment. No objective responses were observed in patients with TNBC or CRPC per RECIST 1.1. Conclusions AMG 900 40 mg/day with G-CSF had manageable toxicity and demonstrated single-agent activity in patients with heavily pretreated, chemotherapy-resistant ovarian cancer.
Keywords: AMG 900; antimitotic; Aurora kinase; pan-Aurora kinase inhibitor
Rights: © 2018, Springer Nature
DOI: 10.1007/s10637-018-0625-6
Appears in Collections:Aurora harvest 4
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