Karyopharm Therapeutics announced detailed results from the pivotal, Phase 3 BOSTON study will be presented at the American Society of Clinical Oncology (ASCO) 2020 Virtual Scientific Program on May 29, 2020. The BOSTON study evaluated once-weekly XPOVIO (selinexor) in combination with once-weekly Velcade (bortezomib) and low-dose dexamethasone (40mg weekly) (SVd) compared to standard twice-weekly Velcade plus low-dose dexamethasone (80mg weekly) (Vd) in patients with multiple myeloma who have received one to three prior lines of therapy. The company previously reported the BOSTON study met its primary endpoint with a significant increase in median progression-free survival (PFS) in patients with multiple myeloma following one to three prior lines of therapy.
BOSTON was a Phase 3 randomized, active comparator-controlled, open-label, multicenter study designed to compare the efficacy, safety and certain health-related quality of life (HR-QoL) parameters of the triple therapy combination in 402 adult patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy. The primary endpoint of the study was progression-free survival (PFS) and key secondary endpoints included overall response rate (ORR), rate of peripheral neuropathy, and others.
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. The SVd group also demonstrated a significantly greater overall response rate (ORR) compared to the Vd group (76.4% vs. 62.3%). Importantly, SVd therapy compared to Vd therapy showed consistent PFS benefit and higher ORR across several important subgroups, including patients 65 years and older, patients who are frail, patients with high-risk cytogenetics, patients with moderate renal impairment and patients whose disease was refractory to bortezomib or lenalidomide, among others.
Data at the time of analysis showed a trend toward an overall survival (OS) benefit associated with SVd therapy with fewer deaths, numerically, reported on the SVd arm (47 vs. 62). Median OS for the SVd arm had not yet been reached as of the data cut-off date of February 18, 2020 while the median OS for the Vd arm was 25.0 months. The median OS for the SVd arm will be reported once it is reached and becomes available.
Peripheral neuropathy rates were significantly lower on SVd compared to Vd (32.3% vs. 47.1%).
The most common treatment-related adverse events (AEs) were cytopenias, along with gastrointestinal and constitutional symptoms.
A supplemental New Drug Application (sNDA) has been submitted to the U.S. Food and Drug Administration (FDA) requesting approval for XPOVIO in combination with Velcade and low dose dexamethasone as a new treatment for patients with previously treated multiple myeloma. The Company also plans to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) requesting approval for the same indication later this year.
About Once Weekly SVd
The once-weekly SVd regimen utilizes 40% less Velcade and 25% less dexamethasone and requires ~37% fewer clinic visits during the first 24 weeks of treatment compared to the standard Vd regimen. Because Velcade is given as a subcutaneous injection rather than as an infusion, clinic visits may be shorter with the SVd regimen than with other non-Velcade regimens that may be employed to treat relapsed multiple myeloma and require intravenous infusions.