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.
Selinexor (KPT-330) is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. Selinexor functions by binding with the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus, which subsequently reinitiates and amplifies their tumor suppressor function. This is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. To date, over 290 patients have been treated with Selinexor in Phase 1 trials in advanced hematologic malignancies and solid tumors. Additional Phase 1 and Phase 2 studies are ongoing or currently planned and three registration-directed clinical trials in hematological indications are expected to begin enrollment during 2014. The latest clinical trial information for Selinexor is available at www.clinicaltrials.gov.
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding the therapeutic potential of and potential clinical development plans for Karyopharm's drug candidates, including the timing of initiation of certain trials and of the reporting of data from such trials. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the company's current expectations. For example, there can be no guarantee that any of Karyopharm's SINE compounds, including Selinexor (KPT-330), or any other drug candidate that Karyopharm is developing will successfully complete necessary preclinical and clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: Karyopharm's results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the
Paul Brannellypaul@karyopharm.com 508-975-4820 Jennifer McNealeyjmcnealey@annesassociates.com 917-392-3400
Source: Karyopharm Therapeutics
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