On April 10, the U.S. Food and Drug Administration (FDA) granted Fast Track designation to the oral selective inhibitor of nuclear export (SINE) compound selinexor for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy.
The FDA’s statement, consistent with the design of the phase IIb STORM study, noted that the three prior lines of therapy include regimens comprising an alkylating agent, a glucocorticoid, bortezomib (Velcade), carfilzomib (Kyprolis), lenalidomide (Revlimid), pomalidomide (Pomalyst), and daratumumab (Darzalex). In addition, the patient’s disease must be refractory to at least one proteasome inhibitor (bortezomib or carfilzomib), one immunomodulatory agent (lenalidomide or pomalidomide), glucocorticoids, and daratumumab, as well as to the most recent therapy. Topline data from the STORM study are expected to be reported at the end of April 2018.
The FDA’s Fast Track program facilitates the development of drugs intended to treat serious conditions and with the potential to address unmet medical needs. A drug program with Fast Track status is afforded greater access to the FDA for the purpose of expediting the drug’s development, review, and potential approval. In addition, the Fast Track program allows for eligibility for Accelerated Approval and Priority Review, if relevant criteria are met, as well as for Rolling Review.
About the STORM Study
In the multicenter, single-arm phase IIb STORM study, approximately 122 patients with heavily pretreated, pentarefractory myeloma receive 80 mg of oral selinexor twice weekly in combination with 20 mg of low-dose dexamethasone, also dosed orally twice weekly.
Overall response rate is the primary endpoint of the study, with duration of response and clinical benefit rate being secondary endpoints. All responses will be adjudicated by an independent review committee.
Selinexor (KPT-330) is a first-in-class, oral 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 2,300 patients have been treated with selinexor, and the drug is currently being evaluated in several mid- and later-phase clinical trials across multiple cancer indications, including in multiple myeloma in a randomized phase III study in combination with bortezomib and low-dose dexamethasone (BOSTON), in combination with low-dose dexamethasone (STORM), and as a potential backbone therapy in combination with approved therapies (STOMP), among others.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.