The US Food and Drug Administration (FDA) has granted orphan designation to selinexor (KPT-330) for the treatment of diffuse large B-cell lymphoma (DLBCL).
The drug elicited responses in patients with non-Hodgkin lymphoma (NHL), including DLBCL, in an ongoing phase 1 study.
Selinexor is a selective inhibitor of nuclear transport that functions by binding to the nuclear export protein XPO1 (also called CRM1). This leads to the accumulation of tumor suppressor proteins in the cell nucleus, which is thought to cause apoptosis in cancer cells while largely sparing normal cells.
The FDA grants orphan designation to promote the development of drugs that target conditions affecting 200,000 or fewer US patients annually and are expected to provide significant therapeutic advantage over existing treatments.
Selinexor’s orphan designation for DLBCL qualifies the drug’s developer, Karyopharm Therapeutics, Inc., for benefits that apply across all stages of development, including an accelerated approval process, 7 years of market exclusivity following marketing approval, tax credits on US clinical trials, eligibility for orphan drug grants, and a waiver of certain administrative fees.
The FDA has also granted selinexor orphan status for the treatment of acute myeloid leukemia.
Phase 1 study
Researchers evaluated selinexor in an ongoing phase 1 study of patients with NHL or chronic lymphocytic leukemia (CLL) and presented results at the 2013 ASH Annual Meeting (abstract 90).
At that time, the study included 18 patients with NHL or CLL. They had a median age of 66.5 years and had received a median of 4.5 prior treatment regimens.
Patients received selinexor at 6 different dose levels. There were no clinically significant cumulative toxicities or cases of major organ dysfunction, and the maximum-tolerated dose was not reached. Researchers continued dosing at 35 mg/m2 twice weekly.
Ten patients experienced drug-related grade 3/4 adverse events, including thrombocytopenia without bleeding (n=6), neutropenia (n=5), dehydration (n=1), syncope (n=1), hypotension (n=1), and fatigue (n=1).
The most common grade 1/2 events were anorexia (n=10), fatigue (n=9), diarrhea (n=6), vomiting (n=6), neutropenia (n=5), malaise (n=3), anemia (n=3), and weight loss (n=3).
Response was evaluable in 15 patients. Eighty percent of patients, all of whom had progressive disease on study entry, experienced tumor shrinkage or disease stabilization on selinexor. The other 20% of patients progressed.
Of 3 patients with DLBCL, 1 progressed, 1 had stable disease, and 1 achieved 93% tumor shrinkage.
“We are encouraged by the response data in patients with DLBCL who have received selinexor in our ongoing phase 1 clinical trial in advanced hematological malignancies,” said Michael G. Kauffman, MD, PhD, Karyopharm’s Chief Executive Officer.
“We plan to present updated clinical data for selinexor across multiple indications, including DLBCL, at ASCO 2014.”
