US-based clinical-stage pharmaceutical firm Karyopharm Therapeutics has started a Phase II trial of its novel, oral Selective Inhibitor of Nuclear Export (SINE) compound Selinexor (KPT-330) for treatment of patients with metastatic hormone-refractory prostate cancer (HRPC).
The company is focused on the discovery and development of new first-in-class drugs directed against nuclear transport targets for treatment of cancer and other major diseases.
Referred to as the SHIP (Selinexor in Hormone Refractory Indications in Prostate Cancer) study, the trial is led by doctors Christopher Logothetis and John Araujo of the MD Anderson Cancer Center at the University of Texas in Houston and is being funded in part by a grant from the Prostate Cancer Foundation.
Karyopharm founder, president and CSO Sharon Shacham said the company recently presented data at ASCO showing an 88% disease control rate, meaning stable disease or better, in eight evaluable patients with heavily pretreated prostate cancer.
"These patients were treated in our Phase I clinical trial of Selinexor in advanced or metastatic solid tumours," Shacham said.
"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 II study to further evaluate Selinexor’s potential in patients with treatment-resistant prostate cancer."
In the trial, a total of 50 qualifying patients with metastatic HRPC following at least one of the recently approved agents (enzalutamide, abiraterone or radium 223) will receive 50mg/m2 of Selinexor orally twice per week over each 28-day cycle.
The trial’s primary goal is to determine the disease control rate assessed according to RECIST criteria and the prevention of new bone lesions, while the secondary goal is to evaluate the prostate-specific antigen (PSA) response relative to baseline.
Logothetis said patients with hormone refractory prostate cancer have very limited options, particularly after their disease progresses on chemotherapy.
"We are encouraged by Selinexor’s disease control rate in the prostate cancer patients with significant bone disease in the ongoing Phase I study, as well as its single-agent activity against a variety of both localized and disseminated prostate cancer in preclinical mouse models," Logothetis said.
Selinexor is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound and it functions by binding with the nuclear export protein XPO1, leading to the accumulation of tumour suppressor proteins in the cell nucleus, which subsequently reinitiates and amplifies their tumour suppressor function.
Image: Micrograph of prostate adenocarcinoma, acinar type, the most common type of prostate cancer. Photo: courtesy of Nephron.