Karyopharm Announces Initiation of a Phase 1 Study of Decitabine (Dacogen) and Selinexor (KPT-330) in Acute Myeloid Leukemia (AML)

Karyopharm Therapeutics Inc. KPTI, a clinical-stage pharmaceutical company focused on the discovery and development of novel first-in-class drugs directed against nuclear transport targets for the treatment of cancer and other major diseases, today announced the initiation of a Phase 1 combination trial of its novel, oral Selective Inhibitor of Nuclear Export (SINE) compound Selinexor (KPT-330) in combination with the DNA methylation inhibitor decitabine (Dacogen®) in patients with relapsed or refractory acute myeloid leukemia (AML) and in patients age ≥60 years with newly diagnosed AML. The study is being conducted at The Ohio State University Comprehensive Cancer Center under the direction of principal investigator Ramiro Garzon, MD, Associate Professor. In this combination study, patients with relapsed and/or refractory AML or newly diagnosed AML patients ≥60 years of age ineligible for intensive chemotherapy will receive decitabine intravenously on days 1-10 and Selinexor orally twice weekly beginning on day 11 of each 31-day cycle. The primary goal of the study is to determine the maximum tolerated dose and the recommended Phase 2 dose of this combination in up to 42 patients. The secondary goal of the study is to determine the response rates and duration of leukemia control. A full description of the study is available at www.clinicaltrials.gov (NCT02093403). Dr. Garzon stated, "We are excited to initiate this study on the combination of the novel oral SINE compound Selinexor with decitabine in patients with relapsed or refractory AML and in elderly AML patients who are not fit for intensive chemotherapy, particularly because of the limited treatment options available to this patient population. We look forward to presenting the initial results of this study later this year." Preclinical results from Dr. Garzon's laboratory, as well as other laboratories, have shown that Selinexor, a SINE compound that covalently inhibits the nuclear export protein XPO1 (exportin 1, also called CRM1), has potent anti-AML activity in vitro and in vivo. This activity is associated with enhancement of nuclear levels of tumor suppressor proteins as well as down-regulation of oncogenic kinases such as FLT3 and c-KIT. Oral Selinexor has shown single agent anti-leukemic activity in patients with heavily pretreated, relapsed/refractory AML. Decitabine has well described anti-AML activity, and this activity correlates with levels of the microRNA miR-29b. Interestingly, XPO1 inhibition enhances nuclear levels of miR-29b, and the combination of Selinexor and decitabine has shown synergy with good tolerability in preclinical in vivo models of AML. Sharon Shacham, PhD, MBA, Karyopharm's founder, President and Chief Scientific Officer, commented, "This first combination study of Selinexor represents a significant milestone for the company as we look to broaden the scope of SINE compounds in the treatment of cancers. We are pleased to expand our relationship with Dr. Garzon and his team at The Ohio State University as we build on his preclinical work with Selinexor in combination with decitabine and its translation into the clinic."