06/19/2019 | Press release | Distributed by Public on 06/19/2019 09:43
Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a clinical-stage pharmaceutical company, today reported updated results from the Phase 2b SADAL (Selinexor Against Diffuse Aggressive Lymphoma) study evaluating selinexor, the Company's first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound, in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after at least two prior multi-agent therapies and who are ineligible for transplantation, including high dose chemotherapy with stem cell rescue and CAR-T (chimeric antigen receptor modified T cell) therapy. The data were highlighted in an oral presentation at the 2019 International Conference on Malignant Lymphoma (ICML) being held June 18-22, 2019, in Lugano, Switzerland.
Top-line results for the SADAL study were previously presented at the American Society of Hematology (ASH) 2018 Annual Meeting in December 2018. The results being presented at ICML remain consistent with those reported at ASH and include efficacy results from the final 12 patients who had not reached their first response assessment in time to be included in the previously released top-line efficacy analyses. For the SADAL study's primary endpoint, single-agent selinexor achieved an overall response rate (ORR) of 28.3%. Two additional patients achieved a complete response (CR) since the ASH presentation for a total of 13 CRs and a CR rate of 10.2% in these patients with heavily pretreated relapsed or refractory DLBCL. Key secondary endpoints included a median duration of response (DOR) in the responding patients of 9.2 months and median overall survival (OS) across the entire study population of 9.0 months.
'Single-agent oral selinexor continues to demonstrate encouraging response rates in these heavily pretreated patients with DLBCL who have received two or more prior therapies and are not eligible for transplantation or CAR-T therapy, and have limited therapies available to treat their disease,' said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. 'We look forward to sharing these data with the U.S. and European regulatory authorities and plan to seek regulatory approval of selinexor as a potential new therapeutic option for patients battling highly refractory DLBCL.'
Karyopharm expects to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) and a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in the first half of 2020. These submissions will include requests for accelerated approval and conditional approval, respectively, of selinexor as a treatment for patients with relapsed or refractory DLBCL after at least two prior multi-agent therapies and who are ineligible for stem cell transplantation, including CAR-T therapies. In addition to Orphan Drug Designation, selinexor was granted Fast Track designation by the FDA in 2018 for the patient population evaluated in the SADAL study.
Updated Phase 2b SADAL Results
Among the 127 patients (median of 2 prior treatment regimens with a range 1-6) who were evaluable for response, as adjudicated by an independent central radiological committee, 36 patients responded (13 CRs and 23 partial responses (PRs)) for an ORR of 28.3%. An additional 11 patients experienced stable disease (SD) for a disease control rate of 37.0%. Selinexor also demonstrated deep and durable responses in patients with either GCB or non-GCB subtypes of DLBCL: the ORR in the 59 patients with the GCB-subtype was 33.9% and the ORR was 20.6% in the 63 patients with the non-GCB subtype. In addition, there were 5 patients enrolled whose subtype was unclassified and 1 of these patients achieved a CR while 2 of these patients achieved a PR.
The median DOR across responding patients was 9.2 months and responses tended to occur rapidly. Median OS for the entire patient population was 9.0 months while median OS has not yet been reached in patients who achieved either a CR or PR. Patients whose disease progressed or had no response to selinexor had a median OS of 4.1 months, which is consistent with the expected poor prognosis for patients who have relapsed or refractory DLBCL and have been previously treated with 2 or more lines of therapy.
All 127 patients were included in the safety analyses. The most common treatment-related adverse events (AEs) were cytopenias along with gastrointestinal and constitutional symptoms and were generally reversible and managed with dose modifications and/or standard supportive care. The most common non-hematologic AEs were nausea (52.8%), fatigue (37.8%), and anorexia (34.6%) and were mostly Grade 1 and 2 events. As expected, the most common Grade 3 and 4 AEs were thrombocytopenia (39.4%), neutropenia (20.5%) and anemia (13.4%) and were generally not associated with clinical sequelae.
Details for the ICML 2019 oral presentation are as follows:
Title: A Phase 2b Study of Selinexor in Patients with Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL): SADAL Trial
Lead author: Nagesh Kalakonda, University of Liverpool
Abstract #: 031
Session: Focus On: Results from Single-Agent Trials
Date and Time: Wednesday, June 19, 2019; 17:25 - 17:45 CEST
Location: Auditorium (USI Università)