A new pivotal phase 3 clinical trial assessing the safety and efficacy of selinexor in combination with ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis (MF) has started.
The initiation of the randomized, double-blind, placebo-controlled study is supported by results from the phase 1 portion of the study demonstrating a 78.6% reduction in patients’ spleen volume and a 58.3% symptom improvement in intent to treat patients at week 24 at a dose of 60 mg.
“We believe that an opportunity exists to expand upon the initial response, depth, and duration of JAK inhibitors to ultimately improve patient outcomes,” said Reshma Rangwala, MD, PhD, the chief medical officer of Karyopharm, the developers on the treatment in a press release from the company.
Read more about the treatment of MF
“This combination has the potential to become a cornerstone treatment in front-line myelofibrosis and we are excited to start this pivotal trial to deliver on our goal of bringing forward an innovative new approach for the treatment of myelofibrosis that can benefit MF patients.”
The phase 3 trial aims to enroll 306 patients, who are at least 18 years of age, with intermediate or high-risk MF who have never been treated with a JAK inhibitor previously.
Participants will randomly be divided into 2 groups at a 2 to 1 ratio. Those in the first group will receive ruxolitinib plus 60 mg selinexor while those in the second, will get ruxolitinib plus placebo in 28-day cycles. The dose of ruxolitinib will be determined by the investigators according to the patients’ platelet count at baseline.
The primary endpoints are the spleen volume response rate of at least 35% and symptom improvement of at least 50% at week 24. The key secondary endpoint is anemia response at week 24.
The trial is estimated to be completed by March 2028 with top-line data readout expected in 2025.
Selinexor, marketed under the brand name Xpovio® is a first-in-class, oral exportin 1 inhibitor and a selective inhibitor of nuclear export compounds. The treatment has already been approved in the United States for the treatment of many cancers on its own or other agents.
References
Karyopharm initiates pivotal phase 3 study of XPO1 inhibitor selinexor and ruxolitinib in JAK inhibitor (JAKi) naïve myelofibrosis. News release. Karyopharm Therapeutics; June 28, 2023.
Study of selinexor in combination with ruxolitinib in myelofibrosis. US National Library of Medicine. Updated July 3, 2023. Accessed July 10, 2023.
