Karyopharm Initiates Third Registration-Directed Clinical Trial of Oral Selinexor

Karyopharm Therapeutics Inc.

, a clinical-stage pharmaceutical company, today announced the initiation of the SADAL study, (Selinexor and Dexamethasone in Aggressive Lymphoma), a registration-directed, Phase 2b study of Selinexor (KPT-330), in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). This randomized, multi-center study of Selinexor, one of the company's novel, oral Selective Inhibitor of Nuclear Export/SINE™ compounds, is being evaluated as a single agent in combination with dexamethasone for supportive care and is expected to enroll approximately 200 patients in approximately 90 sites worldwide. Karyopharm has received Orphan Drug Designation from the U.S Food and Drug Administration (FDA) and European Medicines Agency (EMA) for Selinexor for the treatment of patients with DLBCL. This open-label Phase 2b study will evaluate the safety and efficacy of high dose (100 mg) versus mid dose (60 mg) Selinexor in combination with low dose (8-12 mg) dexamethasone for supportive care, each given orally to approximately 200 patients (100 per arm) with relapsed/refractory DLBCL. Overall response rate (ORR) is the primary endpoint. The study is expected to take approximately two years to complete and is intended to support accelerated regulatory approval. This study was designed in consultation with the FDA and on the basis of data from Karyopharm's ongoing Phase 1 study of Selinexor in patients with advanced hematologic malignancies. In that ongoing Phase 1 study, as of December 1, 2014, data from heavily pretreated patients with relapsed/refractory DLBCL and other types of non-Hodgkin's lymphoma (NHL) show: median duration of response (DOR) of approximately 7 months for Selinexor in patients with NHL; a 40% ORR in aggressive B-cell NHL, including four of 10 partial responses (PRs), in patients treated with high-dose (≥ 60 mg/m2 equivalent to >100 mg) Selinexor, and a 37% ORR, including four complete responses (CRs) and three PRs, in patients treated with mid-dose (20-50 mg/m2 equivalent to ~60mg) Selinexor; and anti-tumor activity across DLBCL subtypes, including 36% and 40% ORRs in patients known to have the Germinal Center B-Cell like (GCB) or non-GCB subtypes, respectively, as well as a 50% ORR (1 CR, 1 PR) in four patients with "double-hit" DLBCL. "This study in DLBCL is the third registration-directed study initiated for Selinexor this year. In June we initiated a registration-directed study evaluating Selinexor in patients with acute myeloid leukemia and in November we initiated a registration-directed study evaluating Selinexor in patients with Richter's Transformation," said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. "We are very encouraged by the responses and durability demonstrated to-date in patients with DLBCL and look forward to continuing to evaluate Selinexor in this patient population. Our goal is to accelerate development of Selinexor in severe hematologic indications with great unmet need while simultaneously broadening the scope of our development efforts in other hematologic and solid tumor indications."