On October 21, 2021 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported dosing of the first patient in the Phase 2 expansion of an ongoing open-label Phase 1/2 study investigating eltanexor, a novel oral, Selective Inhibitor of Nuclear Export (SINE) compound, as a single-agent or in combination with approved and investigational agents in patients with several types of hematologic and solid tumor cancers (KCP-8602-801; NCT02649790) (Press release, Karyopharm, OCT 21, 2021, View Source [SID1234591692]). The Phase 2 expansion is designed to evaluate eltanexor monotherapy in patients with hypomethylating agents (HMA) refractory, intermediate or high-risk myelodysplastic syndrome (MDS). The primary endpoint for this Phase 2 expansion is overall response rate (ORR) with the secondary endpoints of determining progression-free and overall survival.
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Initiation of the Phase 2 expansion follows encouraging results from the Phase 1 portion of the study where single-agent eltanexor showed activity in patients with high-risk, relapsed MDS that was refractory to HMAs. In that study (Sangmin, et al. EHA (Free EHA Whitepaper) 2021), eltanexor demonstrated a 53% ORR and a median overall survival of 9.9 months, comparing favorably to historical controls. At the recommended Phase 2 dose of 10 mg, eltanexor monotherapy was well tolerated with low incidence and grade of gastrointestinal events. Exacerbation of cytopenias occurred in 20-40% of patients. Based on these promising signals, the study has been expanded to include an additional 83 patients with the first patient recently dosed.
"MDS is a group of diseases characterized by ineffective production of the components of the blood due to poor bone marrow function, leading to a high risk of transformation into acute leukemia. HMAs are the current standard of care for patients with newly diagnosed, higher-risk MDS, however only 40-60% patients respond, with these responses typically lasting less than two years. As such, prognosis in HMA refractory disease is poor, with a median overall survival of four to six months. With no agents currently approved for primary HMA refractory MDS, the need for novel, efficacious agents is critical. Based on the promising signal observed in the prior Phase 1 study, we are pleased to initiate dosing in the Phase 2 expansion and look forward to updating you on the progress of this important study in the future," said Sharon Shacham, PhD, MBA, Co-Founder and Chief Scientific Officer of Karyopharm.
About Eltanexor
Eltanexor (KPT-8602) is an investigational novel SINE compound that, like selinexor, functions by binding with, and inhibiting, the nuclear export protein, XPO1, leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells.
In preclinical models, eltanexor has a broad therapeutic window with minimal penetration of the blood brain barrier and, therefore, has the potential to serve as another SINE compound for cancer indications. Following oral administration, animals treated with eltanexor show lower percentage of body weight loss and improved food consumption than animals similarly treated with selinexor. This allows more frequent dosing of eltanexor, enabling a longer period of exposure at higher levels than is possible with selinexor. As a result, we believe that eltanexor represents another novel SINE compound and we are evaluating its safety, tolerability and efficacy in ongoing clinical studies.
Eltanexor is an investigational medicine and has not been approved by the United States Food and Drug Administration, Health Canada, the European Medicines Agency, or any other regulatory agency.