Karyopharm Reports Positive Top-Line Phase 2b SADAL Data for Selinexor in Patients with Diffuse Large B-Cell Lymphoma at the American Society of Hematology 2018 Annual Meeting
-- 29.6% Overall Response Rate Including 9.6% Complete Response Rate --
-- Amongst the Patients with Complete or Partial Response, Median Duration of Response was 9.2 Months and Median Overall Survival was 29.7 months --
-- Company Plans to Submit New Drug Application to the
Selinexor recently received Fast Track designation from the
Top-Line Phase 2b SADAL Results
Based on the modified intention-to-treat analysis from the first 115 of 127 patients (median of 2 prior treatment regimens with a range 1-6), as adjudicated by an independent central radiological committee, 34 patients responded (11 patients with a CR and 23 patients with a PR) for an ORR of 29.6%. An additional 8 patients experienced stable disease (SD) for a disease control rate of 36.5%. The median DOR across responding patients was 9.2 months and responses tended to occur rapidly. Patients with a CR had a median DOR of 23.0 months and patients with a PR had a median DOR of 7.8 months. As of the data cutoff date of
Among the patients evaluated for safety as of the data cutoff date, the most common treatment-related adverse events (AEs) were gastrointestinal and constitutional symptoms, along with cytopenias; most manageable with dose modifications and/or supportive care. The most common non-hematologic AEs were nausea (50.0%), fatigue (35.9%), and anorexia (32.0%) and mostly Grade 1 and 2 events. As expected, the most common Grade 3 and 4 AEs were thrombocytopenia (35.2%), neutropenia (20.3%), and anemia (10.9%) and were generally not associated with clinical sequelae. No significant major organ toxicities were observed, and bleeding and infection rates were low.
The median OS was 9.1 months for all patients in the study. As of the data cutoff date, median survival for the patients with a CR or PR was 29.7 months. The median survival for patients with best response of progressive disease or who were not evaluable for response was 3.2 months.
Selinexor showed robust, single-agent activity in patients with either GCB or non-GCB subtypes of DLBCL: of the 53 patients with the GCB-subtype, 18 responded (5 patients with a CR and 13 patients with a PR) for an ORR of 34.0%. Of the 57 patients with the non-GCB subtype, 12 responded (6 patients with a CR and 6 patients with a PR) for an ORR of 21.1%. In addition, there were 5 patients enrolled whose subtype was unclassified and 4 of these patients achieved a PR.
“The SADAL data presented at ASH this year demonstrate that oral selinexor, when administered as a single-agent, is clinically active and capable of producing durable responses associated with prolonged overall survival,” said Marie Maerevoet, MD, Institute Jules Bordet, “The 60mg twice weekly oral dose continues to be well tolerated with a low incidence of Grade 3 or greater adverse events, which were often manageable with dose modifications and supportive care. We are highly encouraged by the results of this single agent study in patients with heavily pretreated DLBCL who have limited available treatment options.”
Details for the Poster Presentation at ASH 2018:
Title: 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
Presenter: Marie Maerevoet, Institute Jules Bordet,
Abstract Number/Publication ID: 1677
Session: 626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Prospective Clinical Trials: Poster I
Date and Time:
Selinexor is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. To date, over 2,800 patients have been treated with selinexor. In April and
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding our expectations relating to submissions and to the review and potential approval of selinexor by regulatory authorities, including the anticipated timing of such submissions and actions, and the potential availability of accelerated approval pathways, the therapeutic potential of and potential clinical development plans for Karyopharm's drug candidates, especially selinexor, and the plans for commercialization. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm’s control, that may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no guarantee that regulators will agree that selinexor qualifies for accelerated approval in the U.S. or conditional approval in the E.U. as a result of the data from the STORM study in patients with penta-refractory myeloma or the SADAL study in patients with relapsed or refractory DLBCL or that any of Karyopharm's drug candidates, including selinexor, will successfully complete necessary clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: Karyopharm's results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the
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Source: Karyopharm Therapeutics Inc.