The U.S. Food and Drug Administration has granted fast track status to Karyopharm Therapeutics‘ investigational oral therapy selinexor for people with diffuse large B-cell lymphoma (DLBCL) who have received two or more prior therapies and are not eligible for stem cell transplant or CAR T-cell therapy.
The designation is meant to speed the development and review of potential therapies for serious conditions with the aim of filling an unmet medical need. It enables more frequent communication with the FDA regarding clinical trials’ designs and collection of all data needed for regulatory approval. Treatment candidates on fast track status also may benefit from accelerated approval and priority review.
“The receipt of Fast Track designation from the FDA for selinexor in relapsed DLBCL underscores the great unmet medical need for this aggressive form of lymphoma,” Sharon Shacham, PhD, founder, president and chief scientific officer of Karyopharm, said in a press release.
The agency’s decision follows review of the open-label SADAL Phase 2b study (NCT02227251), where selinexor induced partial or complete tumor responses in more than one-third of heavily treated DLBCL patients.
The trial included 110 patients who had received two to five prior treatments and were not eligible for a stem cell transplant. Participants — half of whom had germinal center B-cell (GCB) DLBCL — are receiving oral selinexor, 60 mg twice weekly, until their disease progresses or signs of toxicity appear.
SADAL’s primary objective is to determine the proportion of patients who respond to selinexor, with duration of response a key secondary measure.
An interim analysis including 32 patients showed that 11 (34.4%) responded to treatment, including five complete responses. Those responses lasted a median 8.4 months, with some lasting more than 24 months.
Responses were similar among DLBCL subgroups, with 33.3% of patients in the GCB group achieving a partial or complete response after selinexor treatment, versus 35.3% in the non-GCB group.
Patients lived for a median of nine months, but while those who achieved stable disease or disease progression lived only a median 4.1 months, more than half of patients with a complete or partial response were still alive.
The treatment was well-tolerated, with all adverse events successfully managed via dose reductions and supportive care. The most common side effects were fatigue, low platelet levels, anorexia, low neutrophil levels, and anemia.
Researchers will present updated results from SADAL at the American Society of Hematology (ASH) 2018 Annual Meeting, Dec. 1-4 in San Diego, California. Marie Maerevoet, MD, from the Institute Jules Bordet, Brussels, Belgium, will present the poster, “Single Agent Oral Selinexor Demonstrates Deep and Durable Responses in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) in Both GCB and Non-GCB Subtypes: The Phase 2b Sadal Study”
“Pending positive results from the Phase 2b SADAL study, we plan to submit a second [new drug application] to the FDA in the first half of 2019, with a request for accelerated approval, for oral selinexor as a potential new treatment for patients with relapsed or refractory DLBCL,” Shacham said.
Selinexor is a selective inhibitor of nuclear export, or SINE, meant to keep tumor suppressor proteins inside the nucleus. These proteins prevent the abnormal proliferation or induce the death of abnormal cells, and their accumulation leads to the selective death of cancer cells, while sparing normal ones.
The treatment has already received fast track designation for multiple myeloma patients with penta-refractory disease, and Karyopharm has recently asked the U.S. Food and Drug Administration to grant it accelerated approval for this indication. A decision is expected by April.