Karyopharm Therapeutics Inc. has initiated 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 cancers. The research project, 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, both located in Denmark.
Selinexor described as 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.” According to Karyopham, the drug was found to have single-agent activity against a variety of ovarian cancer cell lines and murine xenografts across a variety of genetic backgrounds in several pretrial laboratory tests. In addition. During Phase 1 studies (which are still continuing) Selinexor showed evidence of anti-cancer activity across several solid tumor types, including patients with gynecologic malignancies.
“The 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," explained 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."
Patients will receive Selinexor at a dose of 50mg/m2, twice a week during the Phase 2 trials as a means of “determining the disease control rate assessed according to RECIST criteria. The secondary goal of the study is to evaluate safety and tolerability,” she added.
Quality of life.
Karyopharm Therapeutics is a clinical-stage pharmaceutical firm devoted to the discovery and development of novel first-in-class drugs directed against nuclear transport targets for the
treatment of cancer and other major diseases. To date, more than 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.