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FDA advisory committee calls for more data on selinexor for relapsed multiple myeloma
An FDA advisory committee determined the approval of selinexor for treatment of patients with heavily pretreated multiple myeloma should be delayed until results of a pivotal phase 3 trial are available.
The Oncologic Drugs Advisory Committee — which makes recommendations about new cancer drugs — supported the delay by an 8 to 5 vote. Some committee members who voted in favor of the delay raised questions about whether available data sufficiently support the agent’s risk-benefit profile.
The FDA often follows the advisory committee’s recommendation but is not obligated to do so.
Selinexor (KPT-330, Karyopharm Therapeutics) is a first-in-class, oral selective inhibitor of nuclear export compound.
The drug binds with and inhibits the nuclear export protein XPO1, leading to the accumulation of tumor suppressor proteins in the cell nucleus. The goal of treatment is selective induction of apoptosis in cancer cells while sparing healthy cells.
Karyopharm officials submitted a new drug application seeking approval of selinexor in combination with dexamethasone for treatment of patients with myeloma who received at least three prior therapies, and whose disease was refractory to at least one proteasome inhibitor, at least one immunomodulatory agent and an anti-CD38 monoclonal antibody.
The FDA previously granted fast track, priority review and orphan drug designations to selinexor for this indication based on results of the multicenter, single-arm, phase 2b STORM study.
The study included 122 patients with heavily pretreated penta-refractory myeloma who received 80 mg oral selinexor twice weekly plus 20 mg low-dose dexamethasone twice weekly.
Overall response rate served as the primary endpoint. Secondary endpoints included duration of response and clinical benefit rate.
The company released initial topline data in April 2018.
Updated results — presented in December at ASH Annual Meeting and Exposition — showed a 26.2% overall response rate, which included two stringent complete responses, six very good partial responses and 24 partial responses.
Median duration of response was 4.4 months. Median survival was 8.6 months among the entire cohort, 15.6 months among those who achieved minimal response or better, and 1.7 months among those whose disease progressed or who were not evaluable.
The most common adverse events included thrombocytopenia (all-grade, 67%; grade 3/grade 4, 53%), nausea (67%; 10%), fatigue (68%; 21%), anorexia (50%; 2%), anemia (46%; 28%) and weight loss (46%; 0%).
Four patients died on treatment. These included one death each due to sepsis, respiratory failure and pulmonary embolism. One patient died of an unspecified but unrelated cardiac event.
Karyopharm is conducting the pivotal randomized phase 3 BOSTON study, which will evaluate the addition of selinexor to bortezomib (Velcade, Takeda/Millennium) and dexamethasone.
The multicenter, open-label trial is designed to enroll approximately 360 patients. PFS and ORR will serve as primary endpoints. Secondary endpoints include duration of response and OS.
Topline data from BOSTON are expected by the end of this year.