Karyopharm Therapeutics will soon present interim data from a Phase 2b clinical trial evaluating selinexor (KPT-330), an oral selective inhibitor of the nuclear export compound, in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
The presentation will take place at the European Hematology Association (EHA) 2017 Annual Congress, set for June 22–25 in Madrid, the company said in a press release. Titled “Single Agent Oral Selinexor Exhibits Durable Responses in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) of Both GCB and Non-GCB Subtypes: The Phase 2b SADAL Study,” it will be given by Marie Maerevoet, Institute Jules Bordet, Brussels, Belgium.
Selinexor is a selective inhibitor of the XPO1 protein, a nuclear export protein. Usually, cancer cells get rid of tumor suppressor proteins, because these proteins activate the apoptotic pathways of defective cells and destroy them. By inhibiting their transport, or export, selinexor allows XPO1 proteins to accumulate in the nucleus, leading to the selective induction of cell death in cancer cells.
The multicenter, open-label, randomized, two-arm Phase 2b study, called SADAL (NCT02227251), is still enrolling patients at 130 sites across the U.S. and Europe, and in Canada and Israel. The trial is designed to assess the safety and efficacy of oral selinexor in patients with relapsed or refractory de novo DLBCL, who have no other therapeutic options. In total, 200 patients will be randomized to receive selinexor twice weekly at a high dose (100 mg) or low dose (60 mg) in a 28-day treatment cycle for one year.
Patients are being grouped by the subtype of their DLBCL — germinal center B-cell (GCB) and non-GCB.
Recent data, presented in April at the American Association for Cancer Research (AACR) annual meeting in Washington, D.C., showed that selinexor monotherapy has potent anti-cancer activity in DLBCL patients, including in those with the GCB subtype.
Among the first 67 patients enrolled in the study, 21.5 percent responded to selinexor, with 12.3 percent showing complete response and 9.2 percent a partial response. Responders had a median of three prior treatment regimens.
Patients with GCB had better overall response rates than those with non-GCB (23.5% vs. 19.3%), as did those receiving low dose (26.4% vs. 16.1%), potentially because of better tolerability and lesser drug exposure time.
The most common treatment-related adverse events were nausea, anorexia, vomiting, and fatigue. Frequent grade 3-4 adverse events were fatigue, anemia, and low levels of platelets or of immune cells called neutrophils. More patients on the high-dose arm experienced grade 3-4 fatigue or low platelet levels.
In addition to EHA presentation, data from SADAL will also be presented at the 2017 International Conference on Malignant Lymphoma (ICML), in Lugano, Switzerland, on June 14.
Rene-Olivier Casanovas, Hematologie Clinique, CHU Dijon, France will be presenting the poster, titled “A Phase 2b Randomized Study of Single Agent Selinexor in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL).”
“DLBCL is the most common type of non-Hodgkin lymphoma among adults and there remains a high unmet medical need, particularly in the relapsed and refractory setting for patients who are not eligible for stem cell transplant or who relapse afterward,” said Sharon Shacham, president and chief scientific officer of Karyopharm. “Previously reported data from the ongoing Phase 2b SADAL study showed that treatment with single-agent oral selinexor resulted in robust response rates with prolonged durability in patients with heavily pretreated DLBCL … We look forward to sharing some further detail from the SADAL study with the medical community at EHA and ICML this year.”
Selinexor is being developed to potentially treat a variety of advanced hematologic and solid tumors.
