Karyopharma Says Selinexor Shows 38% Disease Control & 13% Overall Response Rate

Karyopharm Therapeutics Inc. KPTI, a clinical-stage pharmaceutical company, today announced the presentation of positive clinical data for its lead product candidate, Selinexor (KPT-330), a first-in-class, oral Selective Inhibitor of Nuclear Export / SINE™ compound, at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting. In an ongoing Phase 2 clinical trial, single-agent oral selinexor demonstrated anti-tumor activity in patients with recurrent glioblastoma, including brain penetration at clinically relevant drug levels, with a 13% overall response rate and a 38% disease control rate. In an ongoing Phase 1b clinical study of single agent oral selinexor in patients with advanced sarcomas including liposarcoma, durable activity, including longer progression free survival than last prior regimen, was demonstrated. "These clinical data extend clinically relevant levels of selinexor in brain tumors, with tolerable and durable anti-cancer activity and disease control in recurrent glioblastoma, as well as durable stable disease in liposarcoma and other sarcomas. These data provide further support for our broad solid tumor development plans for selinexor as a single-agent and in combination with approved or experimental therapies," said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. In a poster presented on Monday, June 1, 2015, entitled, "A phase 2 study on efficacy, safety and intratumoral pharmacokinetics of oral selinexor (KPT-330) in patients with recurrent glioblastoma (GBM)," Dr. Ullrik Lassen of Rigshospitalet and colleagues described data from an ongoing Phase 2 study of single-agent selinexor in patients with glioblastoma that recurred after temozolomide and radiation therapy, including brain penetration at clinically relevant levels, leading to durable anti-cancer activity and disease control of up to 6 months. All data are as of May 10, 2015. Selinexor dosed twice weekly at 50 mg/m2 demonstrated anti-tumor activity with 13% ORR and 38% DCR in 16 surgically ineligible patients with glioblastoma that had been pretreated with temozolomide and radiation. Response data across these 16 patients were as follows: N DCR PR SD PD 16 6 (38%) 2 (13%) 4 (25%) 10 (62%) Responses allocated according to the Response Assessment in Neuro-Oncology (RANO). DCR=Disease Control Rate (PR+SD), PR=Partial Response, SD=Stable Disease, PD=Progressive Disease Selinexor reaches concentrations in glioblastoma tumors that are active in vitro against patient-derived glioblastoma cells. The most common adverse events were thrombocytopenia, fatigue, anorexia, and hyponatremia. In a poster presented on Sunday, May 31, 2015, entitled, "A phase 1b study with selinexor, a first in class selective inhibitor of nuclear export (SINE) in patients with advanced sarcomas: An efficacy analysis," Dr. Mrinal Gounder of Memorial Sloan Kettering Cancer Center and colleagues described the activity of single-agent selinexor in patients with advanced sarcomas in which durable stable-disease (including tumor shrinkage) was observed. All data are as of May 10, 2015. In 45 evaluable patients receiving single-agent selinexor dosed twice weekly, 27 patients (60%) across a variety of sarcoma types achieved stable disease. Sarcoma Type N SD (%) PD (%) Liposarcoma 18 14 (78%) 4 (22%) Leiomyosarcoma 8 5 (63%) 3 (37%) Others 19 8 (42%) 11 (58%) Total 45 27 (60%) 18 (40%) Responses adjudicated according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). SD=Stable Disease, PD=Progressive Disease Median progression free survival for selinexor was 136 days compared with last prior regimen of 54 days in 11 liposarcoma patients with known time to progression on last prior regimen. Selinexor was generally well tolerated with supportive care for anorexia and nausea. Selinexor was dosed twice-weekly at either 30 mg/m2 (~50 mg), 50 mg/m2 (~80 mg) or 60 mg flat dose. On-treatment biopsies demonstrated the pharmacological activity of selinexor based upon decreased tumor cell numbers, reduced proliferative rates and increased replacement of tumor with stromal tissue compared with pre-treatment biopsies.