Karyopharm announced positive top-line results from the randomized Phase 3 BOSTON study evaluating once-weekly Xpovio (selinexor) in combination with once-weekly Velcade (bortezomib) and low-dose dexamethasone (SVd) compared to standard twice-weekly Velcade plus low-dose dexamethasone (Vd) in patients with multiple myeloma who have received one to three prior lines of therapy. The BOSTON study met its primary endpoint of a statistically significant increase in progression-free survival (PFS).
BOSTON is a randomized, active comparator-controlled, open-label, multicenter study that is designed to compare the efficacy, safety, and certain health-related quality of life (HR-QoL) parameters. The study enrolled approximately 402 patients. The primary endpoint of the study is progression-free survival (PFS) and key secondary endpoints include overall response rate (ORR), among others. Additionally, the BOSTON study allows for patients on the Vd control arm to crossover to the SVd arm following objective (quantitative) progression of disease. The BOSTON study is being conducted at over 150 clinical sites internationally.
The median PFS in the SVd arm was 13.93 months compared to 9.46 months in the Vd arm, representing a 4.47 month (47%) increase in median PFS. There were no new safety signals on the SVd arm and no imbalance in deaths between the two arms in the study. The full top-line data will be submitted for presentation at upcoming medical meetings.
Regulatory submissions for Xpovio for patients with multiple myeloma who have received one to three prior lines of therapy are planned in 2Q 2020.
Xopvio received accelerated approval from the FDA in July of 2019 for the treatment of adult patients with relapsed or refractory multiple myeloma 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. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefits in a confirmatory trial. Karyopharm expects to submit data from the Phase 3 BOSTON study to serve as this confirmatory trial.
About Xpovio (selinexor)
Xpovio is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. Xpovio functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). Xpovio blocks the nuclear export of tumor suppressor, growth, regulatory, and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion.
About Multiple Myeloma
Multiple myeloma is the second most common hematologic malignancy, affecting more than 130,000 patients in the United States. Approximately 32,000 Americans are diagnosed with multiple myeloma each year. Despite available treatments, multiple myeloma remains an incurable malignancy, and is associated with significant patient burden.