Karyopharm initiates Phase 2 study of Selinexor in patients with hormone-refractory prostate cancer

NATICK, Mass.—Karyopharm Therapeutics Inc., 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, has initiated a Phase 2 trial of its novel, oral selective inhibitor of nuclear export (SINE) compound Selinexor (KPT-330) in patients with metastatic hormone-refractory prostate cancer (HRPC). The study, referred to as the SHIP (Selinexor in Hormone Refractory Indications in Prostate Cancer) study, is led by Dr. Christopher J. Logothetis and Dr. John Araujo of the M.D. Anderson Cancer Center at the University of Texas in Houston and is being funded in part by a grant from the Prostate Cancer Foundation.

"We recently presented data at ASCO showing an 88 percent disease control rate, meaning stable disease or better, in eight evaluable patients with heavily pretreated prostate cancer," stated Dr. Sharon Shacham, Karyopharm's founder, president and CSO. "These patients were treated in our Phase 1 clinical trial of Selinexor in advanced or metastatic solid tumors. All had progressive disease upon entering the study and had exhausted available therapies including taxane-based chemotherapy, and many had received newer agents such as enzalutamide and/or abiraterone. As a result of this encouraging data, we have initiated the SHIP study, a Phase 2 study to further evaluate Selinexor's potential in patients with treatment-resistant prostate cancer."

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.

Approximately 50 qualifying patients with metastatic HRPC following at least one of the recently approved agents (enzalutamide, abiraterone or radium 223) will receive 50 mg/m2 of Selinexor orally twice per week over each 28-day cycle. The primary goal of the study is to determine the disease-control rate assessed according to RECIST criteria and the prevention of new bone lesions. The secondary goal of the study is to evaluate the prostate-specific antigen (PSA) response relative to baseline. A full description of the study is available at www.clinicaltrials.gov (NCT02146833).

"Patients with hormone refractory prostate cancer have very limited options, particularly after their disease progresses on chemotherapy," commented Dr. Logothetis. "However, we are encouraged by Selinexor's disease control rate in the prostate cancer patients with significant bone disease in the ongoing Phase 1 study, as well as its single-agent activity against a variety of both localized and disseminated prostate cancer in preclinical mouse models. We look forward to assessing the treatment potential of Selinexor in this patient population where there is a high unmet need for further therapy to control their disease and to prolong their lives."

Approximately one in every seven men in North America will be diagnosed with prostate cancer during his lifetime, according to the American Cancer Society. In men, it is the most common malignancy other than skin malignancies, and the second most common cause of cancer death in North American males. Worldwide, prostate cancer ranks third in cancer incidence and sixth in cancer mortality among men. Despite the recent approvals of novel agents, the American Cancer Society estimates that over 29,000 men in the United States will die of prostate cancer in 2014, indicating the clear medical need for additional novel therapies.

To date, over 300 patients have been treated with Selinexor in Phase 1 and Phase 2 clinical 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.

Karyopharm Therapeutics Inc. is 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. SINE compounds have shown biological activity in models of cancer, autoimmune disease, certain viruses, and wound-healing.