FDA Grants Accelerated Approval to Selinexor for Multiple Myeloma
On July 3, 2019, the U.S. Food and Drug Administration (FDA) granted accelerated approval to selinexor (XpvioTM) in combination with dexamethasone for adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody.
Efficacy was evaluated in 122 patients enrolled in part two of STORM (KCP-330-012; NCT02336815), a multicenter, single-arm, open-label study of patients with RRMM who had previously received three or more anti-myeloma treatment regimens including an alkylating agent, glucocorticoids, bortezomib, carfilzomib, lenalidomide, pomalidomide, and an anti-CD38 monoclonal antibody. In addition, the disease was refractory to glucocorticoids, a proteasome inhibitor, an immunomodulatory agent, an anti-CD38 monoclonal antibody, and to the last line of therapy. These patients were treated with selinexor (80 mg) in combination with dexamethasone (20 mg) on days one and three of every week.
The approval was based on efficacy and safety in a prespecified subgroup analysis of 83 patients whose disease was refractory to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab. The overall response rate was 25.3% (95% CI: 16.4, 36), with one stringent complete responses (CR), no CR, four very good partial responses and 16 partial responses. The median time to first response was four weeks (range: 1 to 10 weeks). The median response duration was 3.8 months (95% CI: 2.3, not estimable). The efficacy evaluation was supported by additional information from an ongoing, randomized trial in patients with multiple myeloma.
Common adverse reactions reported in at least 20% of patients include thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection.
The recommended selinexor dose is 80 mg in combination with dexamethasone taken orally on days one and three of each week.
As a condition of accelerated approval, further clinical trials may be required to verify and describe selinexor’s benefit. FDA granted this application fast track designation and orphan drug designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics).
Project Facilitate: The Oncology Center of Excellence program for Expanded Access—For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 1-800-FDA-1088.
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