Adding Xpovio (selinexor) to Velcade (bortezomib) and low-dose dexamethasone significantly extends survival without signs of disease worsening in people with multiple myeloma who received one to three prior lines of therapy, top-line results from the BOSTON Phase 3 trial show.
The triple combo, given once per week, helped patients live without disease progression for a median of 14 months. That was 4.5 months longer than the period seen in people receiving the standard, twice-weekly Velcade-dexamethasone combo, according to Karyopharm Therapeutics, the therapy’s developer.
BOSTON has met its primary goal, demonstrating that the once-weekly Xpovio combo reduces the risk of disease worsening or death by 30%.
No new safety signs were reported in the triple combo arm, the researchers reported. Additional findings will be presented at upcoming medical meetings.
Karyopharm intends to submit the data to the U.S. Food and Drug Administration (FDA) as part of a supplemental new drug application seeking to expand XPOVIO’s approved use.
“We are thrilled to report these highly significant top-line results from the BOSTON study, the first randomized Phase 3 trial to demonstrate clinically and statistically significant activity of once-weekly Xpovio in combination with a current standard of care treatment in patients with myeloma after one to three prior therapies,” Sharon Shacham, PhD, MBA, president and chief scientific officer of Karyopharm, said in a press release.
“In the study, patients on the [triple-combo] regimen lived 47% longer without their disease worsening, which we believe represents an important improvement in the treatment of patients with relapsed or refractory multiple myeloma,” Shacham said.
Xpovio, Karyopharm’s lead compound, is a selective inhibitor of nuclear export. It suppresses the function of a protein called XPO1, often found at higher levels in tumor cells, which exports tumor suppressor proteins out of the cell’s nucleus. The therapy works by inducing the accumulation of these tumor suppressors in the nucleus, which leads to the selective death of tumor cells.
The FDA granted Xpovio accelerated approval, in combination with the corticosteroid dexamethasone, for treating people with multiple myeloma who had received at least four prior therapies and failed to respond to treatment.
Given in July 2019, that approval allows Xpovio’s use for people whose disease is resistant to several forms of treatment, including at least two proteasome inhibitors, two immunomodulatory agents, and an anti-CD38 monoclonal antibody. These antibodies work by improving host-anti-tumor immunity.
The accelerated approval was based on findings from the multicenter, single-arm, open-label STORM Phase 2b trial (NCT02336815), which showed that a quarter of these heavily treated myeloma patients responded to Xpovio treatment, and that responses lasted a median of 3.8 months.
The researchers note that treatments granted accelerated approval status require a further showing of efficacy in a confirmatory study. That was the main goal of the randomized BOSTON trial (NCT03110562).
BOSTON is assessing if adding Xpovio to treatment with Velcade and low-dose dexamethasone delays disease progression and extends the lives of patients with relapsed or refractory multiple myeloma (RRMM).
It has recruited about 402 participants who had received up to three prior lines of therapy, and randomly assigned them to receive the Xpovio combo, once-weekly, or standard Velcade and low-dose dexamethasone every two weeks.
Karyopharm is now planning to submit the data to the FDA in the first half of 2020, hoping to obtain a full approval for Xpovio and to extend its use as a second-line treatment for RRMM patients, Shacham said.
“If approved, the [Xpovio-Velcade-dexamethasone] regimen would be the first and only FDA-approved combination drug regimen that includes once-weekly Velcade therapy for relapsed myeloma,” she said.
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