Karyopharm Initiates Phase 2 Study of Selinexor in Patients With Advanced Gynecologic Malignancies

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 2 trial of its novel, oral Selective Inhibitor of Nuclear Export (SINE) compound Selinexor (KPT-330) in patients with advanced gynecologic malignancies including cervical, ovarian and uterine carcinomas. The study, referred to as the SIGN Study, is being led by Ignace Vergote, MD, at the University Hospitals, Leuven, Belgium. SIGN is also open at Rigshospitalet in Copenhagen, Aalborg University Hospital, Aalborg, and Herlev Hospital, Herlev, all in Denmark. In this Phase 2 study, patients will receive Selinexor at a dose of 50mg/m2, twice a week. The primary goal of the study is to determine the disease control rate assessed according to RECIST criteria. The secondary goal of the study is to evaluate safety and tolerability. Quality of life will also be evaluated. A full description of the study is available at www.clinicaltrials.gov (NCT02025985). Dr. Vergote commented, "We are very excited to initiate this study with Selinexor in patients with relapsed or refractory carcinomas of the cervix, ovary or uterus. Selinexor has shown intriguing activity in various solid tumor malignancies in the ongoing Phase 1 studies, and we look forward to further evaluating its activity in these difficult-to-treat patients who have limited therapeutic options." "This Phase 2 study in patients with advanced gynecologic malignancies is designed to further characterize the single-agent activity of Selinexor following signals in our ongoing Phase 1 study," said Dr. Sharon Shacham, founder, President and Chief Scientific Officer of Karyopharm. "The activation of multiple tumor suppressor proteins by Selinexor is a mechanism broadly applicable across multiple cancer indications, and may be particularly suited to the complex genetic lesions present in ovarian and other gynecologic malignancies." Selinexor is a covalent inhibitor of the nuclear export protein XPO1 that enhances the accumulation and activation of multiple tumor suppressor proteins in the nucleus. This leads to induction of apoptosis in neoplastic cells, while largely sparing normal cells. Preclinical results from several laboratories have shown that Selinexor has single-agent activity against a variety of ovarian cancer cell lines and murine xenografts across a variety of genetic backgrounds. In an ongoing Phase 1 study in patients with a variety of solid tumors, Selinexor has shown evidence of anti-cancer activity across several tumor types, including patients with gynecologic malignancies. About Selinexor 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. Over 300 patients have been treated with Selinexor in Phase 1 and Phase 2 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.