What is Selinexor (KPT-330)?
Selinexor, also known as KPT-330, is a new oral novel agent being developed by Karyopharm Therapeutics. Selinexor is the first drug in a new class of agents known as Selective Inhibitor of Nuclear Export (SINE™) compounds. Selinexor works by inhibiting XPO1, a protein found in the nucleus of cancer cells, which activates tumor suppressors by retaining them in the nucleus of cancer cells. This results in apoptosis (death) of cancer cells, while largely sparing normal cells. Selinexor also reduces the levels of onco-proteins such as c-myc and bcl-2, thereby reducing the growth of cancer cells.
To date, over 1,200 patients with hematologic malignancies, including multiple myeloma, or with solid tumors have been treated with selinexor in clinical trials. Preliminary results from a phase I trial of selinexor in combination with dexamethasone in patients with relapsed multiple myeloma are encouraging. Sixty percent (6 out of 10) patients achieved a response (partial or better) with one patient achieving a complete remission. The most common side effects of selinexor include nausea, vomiting, anorexia and fatigue. These symptoms may be managed with standard anti-nausea medications and tend to lessen following the first 1 – 2 months of treatment. Additionally, patients may have a reduction in the number of platelets, although bleeding and bruising events are rare.
Several clinical trials investigating selinexor in multiple myeloma in combination with established therapies are ongoing.
- STORM Trial: is a multi-center trial enrolling in the U.S. and Canada to evaluate the safety and efficacy of selinexor plus dexamethasone in multiple myeloma patients who have previously received bortezomib, lenalidomide, carfilzomib and pomalidomide and are refractory to or relapsed on their last proteasome inhibitor and IMid therapies.
- STOMP Trial: is a multi-center trial in the U.S. and Canada to evaluate the safety and efficacy of selinexor plus dexamethasone in combination with bortezomib, lenalidomide or pomalidomide in patients who are refractory to or relapsed after previous proteasome inhibitor or IMid therapy.
The University of Chicago in collaboration with the NCI and in coordination with the MMRF/MMRC are also conducting a phase I trial to evaluate selinexor plus dexamethasone in combination with carfilzomib.
Contact the MMRF to learn more about these trials.