Phase I trial of SAR103168, a novel multi-kinase inhibitor, in patients with refractory/relapsed acute leukemia or high-risk myelodysplastic syndrome

• Type of Material: Article
• Authors: Gail J. Roboz, Weill Medical College of Cornell University; Hanna Khoury, Emory University; Elias Jabbour, The University of Texas MD Anderson Cancer Center; Wilena Session, Emory University; Ellen K. Ritchie, Weill Medical College of Cornell University; Harry Miao, Sanofi Oncology; Stefan Faderl, The University of Texas MD Anderson Cancer Center; Wei Zheng, Sanofi Oncology; Eric J Feldman, Weill Medical College of Cornell University; Martha Arellano, Emory University; J. Gilmour Morrison, Covance Laboratories; Farhad Ravandi, The University of Texas MD Anderson Cancer Center
• Language: English
• Date: 2015-02-01
• Publisher: Taylor & Francis
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 Informa UK, Ltd.
• Final Published Version (URL): http://dx.doi.org/10.3109/10428194.2014.918970
• Title of Journal or Parent Work: Leukemia & Lymphoma
• ISSN: 1042-8194
• Volume: 56
• Issue: 2
• Start Page: 395
• End Page: 400
• Keywords: ACUTE MYELOID-LEUKEMIA; AML; MDS; multi-kinase inhibitor; SAR103168; Science & Technology; Life Sciences & Biomedicine; Hematology; Oncology
• Research Categories: Health Sciences, Oncology; Health Sciences, Public Health

Abstract

There is no effective treatment for relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). We conducted a phase I dose escalation trial of SAR103168, a novel multi-targeted kinase inhibitor with activity against the Src kinase family, the BCR-Abl kinase and several angiogenic receptor kinases. Twenty-nine patients 18-83 years old were treated with SAR103168. Pharmacokinetics was characterized by plasma peak concentration (Cmax) at the end of the infusion, followed by a biphasic decline in the elimination profile. Adverse events were as expected for the patient population and there were no individual toxicities specific to SAR103168. Due to the unpredictable nature of drug exposure, the sponsor decided to discontinue the study prior to reaching the maximum tolerated dose.