Massachusetts–based Karyopharm Therapeutics announced that the first patient was dosed in its pivotal BOSTON Phase 3 clinical trial designed to evaluate selinexor (KPT-330) in combination with Velcade (bortezomib) and dexamethasone for the treatment of relapsed or refractory multiple myeloma.
This pivotal, multicenter, randomized, open-label trial (NCT03110562) is currently recruiting participants, and is projected to complete enrollment in 2018. Top-line data should be released in 2019.
Selinexor is Karyopharm’s new lead oral selective inhibitor of nuclear export (SINE) compound. It functions by binding to and inhibiting the nuclear export protein SPO1, causing accumulation of tumor-suppressing proteins in the cell nucleus. This reinitiates and boosts the tumor suppressor function and is believed to lead to the selective induction of death in cancer cells while largely sparing normal cells.
The study is designed to enroll approximately 360 patients who received one to three prior lines of therapy, and will evaluate the safety and efficacy of selinexor in combination with Velcade and low-dose dexamethasone (SVd), compared to Velcade and low-dose dexamethasone alone (Vd).
The study allows patients on the control arm to cross over to the active arm after disease progression. The company expects to include over 100 trial sites worldwide.
The study will assess the time to disease progression or death from any cause as its primary endpoint. Secondary endpoints include duration of response (DOR) and overall survival (OS), among others.
The BOSTON study is supported by comprehensive clinical data from the ongoing Phase 1b/2 STOMP study (NCT02343042), where the SVd combination achieved high response rates in patients with heavily pretreated multiple myeloma.
“Based on clinical and preclinical data to date, we believe that the combination of selinexor, Velcade and dexamethasone (SVd) could have multiple benefits for patients,” Michael G. Kauffman, MD, PhD, chief executive officer of Karyopharm, said in a press release. “In the studies to date, the dosing schedule and regimen required fewer clinic visits for patients and had a manageable side effect profile, including rates of peripheral neuropathy, which have been significantly lower in SVd clinical data to date, compared to the historical rates of peripheral neuropathy in the standard Vd dosing regimen.”
“We also believe that the SVd combination may resensitize myeloma cells to Velcade and other proteasome inhibitors,” he added. “Clinical data to date have demonstrated a significantly higher response rate in patients who have been exposed to a proteasome inhibitor and then receive a combination of a proteasome inhibitor, selinexor and dexamethasone, compared to historical response rates with the retreatment of a proteasome inhibitor and dexamethasone alone.”