Date: 2015-03-28
Type of information: Initiation of the trial
phase: 2
Announcement: initiation of the trial
Company: Karyopharm Therapeutics (USA - MA)
Product: selinexor (KPT-330 - (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-N'-(pyrazin-2-yl)acrylohydrazide)
Action
mechanism: selective inhibitor of nuclear export/nucleoside analogue. Selinexor (KPT-330) is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. Selinexor functions by binding to the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus, which subsequently reinitiates and amplifies their tumor suppressor function. This is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. To date, over 300 patients have been treated with Selinexor in Phase 1 and Phase 2 clinical trials in advanced hematologic malignancies and solid tumors. Additional Phase 1 and Phase 2 studies are ongoing or currently planned and three registration-directed clinical trials in hematological indications are expected to begin enrollment during 2014.
Disease: multiple myeloma
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: The STORM study (Selinexor Treatment of Refractory Myeloma) is a multi-center, single-arm Phase 2 study of selinexor (KPT-330) in heavily-pretreated patients with quad-refractory multiple myeloma. Selinexor will be evaluated in combination with low-dose dexamethasone in multiple myeloma patients whose disease was refractory to treatment with bortezomib (Velcade®), lenalidomide (Revlimid®), carfilzomib (Kyprolis®) and pomalidomide (Pomalyst®). The first cohort will enroll approximately 80 patients at about 30 sites, primarily in the United States, with ~25% of the patients also having received treatment with an anti-CD38 monoclonal antibody such as daratumumab. The study will evaluate the safety and efficacy of a fixed dose of selinexor (80 mg) plus low dose dexamethasone (20 mg). Each compound will be given orally twice weekly to approximately 80 patients with multiple myeloma with quad-refractory multiple myeloma. In addition, patients will have received alkylating agents and glucocorticoids, and their myeloma must be refractory to their most recent therapy. Overall response rate (ORR) is the primary endpoint of the study and this endpoint has served as the basis for accelerated approvals in multiple myeloma for other agents. STORM was designed based on data from Karyopharm's Phase 1 study of selinexor in combination with low dose dexamethasone in relapsed/refractory multiple myeloma. (NCT02336815)
Latest
news: * On May 28, 2015, Karyopharm Therapeutics announced the initiation of the STORM study (Selinexor Treatment of Refractory Myeloma). Selinexor will be evaluated in combination with low-dose dexamethasone in multiple myeloma patients whose disease was refractory to treatment with bortezomib (Velcade®), lenalidomide (Revlimid®), carfilzomib (Kyprolis®) and pomalidomide (Pomalyst®). Depending on the results from this initial cohort, the trial may be expanded to include additional patients. As of December 1, 2014, Phase 1/2 data from ten heavily pretreated myeloma patients (median of seven prior therapies), nine of whom were evaluable for response, demonstrated a 67% ORR (partial response or better) and an 89% clinical benefit rate (minimal response or better). The overall median duration of response, measuring time from response to progression, is approximately seven months.
