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dc.contributor.authorCarducci, M.-
dc.contributor.authorShaheen, M.-
dc.contributor.authorMarkman, B.-
dc.contributor.authorHurvitz, S.-
dc.contributor.authorMahadevan, D.-
dc.contributor.authorKotasek, D.-
dc.contributor.authorGoodman, O.-
dc.contributor.authorRasmussen, E.-
dc.contributor.authorChow, V.-
dc.contributor.authorJuan, G.-
dc.contributor.authorFriberg, G.-
dc.contributor.authorGamelin, E.-
dc.contributor.authorVogl, F.-
dc.contributor.authorDesai, J.-
dc.identifier.citationInvestigational New Drugs, 2018; 36(6):1060-1071-
dc.description.abstractBackground 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 ( : 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.-
dc.description.statementofresponsibilityMichael Carducci, Montaser Shaheen, Ben Markman, Sara Hurvitz, Daruka Mahadevan, Dusan Kotasek ... et al.-
dc.rights© 2018, Springer Nature-
dc.subjectAMG 900; antimitotic; Aurora kinase; pan-Aurora kinase inhibitor-
dc.titleA phase 1, first-in-human study of AMG 900, an orally administered pan-Aurora kinase inhibitor, in adult patients with advanced solid tumors-
dc.typeJournal article-
Appears in Collections:Aurora harvest 4
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