Researchers at the University of Utah’s Huntsman Cancer Institute discovered in laboratory studies that an experimental drug called selinexor may block a crucial survival pathway exploited by myelofibrosis cells. Their study was recently published in Clinical Cancer Research. Based on their preclinical findings, the Utah-based team designed a clinical trial now open at Huntsman to examine the drug’s effectiveness in patients with myelofibrosis.
TrialSite News provides a brief overview of the study but first a description of Myelofibrosis. For a deeper dive into the background as to how the Huntsman team uncovered selinexor follow the link below to the EurekAlert! press release.
What is Myelofibrosis?
Rare cancer that prevents the bone marrow from making healthy blood cells, Myelofibrosis is deadly. Most patients will not live beyond five years after the diagnosis. Huntsman Cancer Institute treats about 25 newly diagnosed patients per year.
Myelofibrosis is a progressive, chronic disease in which the bone marrow is replaced by fibrous tissue and blood is made in organs such as the liver and the spleen, instead of in the bone marrow. The disease is marked by an enlarged spleen and progressive anemia. Also called agnogenic myeloid metaplasia, chronic idiopathic myelofibrosis, idiopathic myelofibrosis, and myelosclerosis with myeloid metaplasia according to the NCI definition.
The one known curative treatment is allogeneic stem cell transplantation, but this approach involves significant risks. Other treatments are largely supportive and do not alter the course of the disorder (with the possible exception of ruxolitinib). Options to support the patient could include regular folic acid, allopurinol or blood transfusions. Lenalidomide and thalidomide may be used in its treatment, though peripheral neuropathy is a common troublesome side-effect.
Selinexor is being commercialized by Karyopharm Therapeutics. It is a first-in-class oral Selective Inhibitor of Nuclear Export (SINE) compound. It funds by binding with and inhibiting, the nuclear export protein, XPO1, leading the accumulation of tumor suppressor proteins in the cell nucleus. This reinstates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells reports Karyopharm Therapeutics.
FDA Recent Rejection for Multiple Myeloma—Need more Evidence
Recently the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted against a recommendation for selinexor (Karyopharm Therapeutics), which is seeking an indication for patients with relapsed-refractory multiple myeloma, due to committee members inability to determine whether the benefits outweighed the risks.
A Phase II, open-label, prospective, single-arm study, the sponsor (University of Utah Huntsman) and collaborator (Karyopharm Therapeutics Inc.) are evaluating the efficacy and safety of selinexor in patients with PMF or secondary MF (PPV-MF or PET-MF) who are refractory or intolerant to ruxolitinib and/or any other experimental JAK1/2 inhibitors.
The sponsor seeks 55 participants and will conduct the study all the way to March 2025.
Study Funding Support
The research is supported by the following:
- National Cancer Institute
- The Hope Foundation for Cancer Research (part of the SWOG Cancer Research Network)
- American Society of Hematology, Leukemia & Lymphoma Society
- Huntsman Cancer Foundation