The results bring hope to these difficult-to-treat patients whose disease continues to progress despite taking available therapies and have exhausted approved treatments.
Tumor suppressor proteins prevent the abnormal proliferation or induce the death of abnormal cells. To escape the effect of these proteins, tumors often increase the levels of XPO1, a protein that exports tumor suppressor proteins from the nucleus into the cytoplasm.
Selinexor, Karyopharm Therapeutics’ lead oral therapy under development, works against this tumor evasion mechanism by suppressing the function of XPO1 – called a Selective Inhibitor of Nuclear Export, or SINE.
This results in the accumulation of tumor-suppressor proteins inside the nucleus of the cell, leading to the selective induction of cell death in cancer cells while sparing normal ones.
Selinexor is being evaluated as a potential treatment for several cancers, namely multiple myeloma. The Phase 2b STORM trial (NCT02336815) was designed to evaluate selinexor in combination with low-dose dexamethasone in heavily treated patients with refractory multiple myeloma.
Its main goal is to determine the proportion of patients achieving a partial or complete response to treatment. The trial is still recruiting previously treated myeloma patients in the U.S., the E.U., and Greece. For information, visit the official clinical trial webpage here.
The first part of this open-label, multicenter study involved 78 patients, 48 of them with quad-refractory disease, and 30 with penta-refractory disease.
Quad-refractory patients are those who received prior treatment with two immunomodulatory drugs, Revlimid (lenalidomide) and Pomalyst (pomalidomide), and two proteasome inhibitors, Velcade (bortezomib) and Kyprolis (carfilzomib).
Also, quad-refractory patients’ disease does not respond to at least one proteasome inhibitor and one immunomodulatory drug, and has progressed following their most recent therapy.
Those with penta-refractory disease are similar to patients with quad-refractory disease, but are also refractory to an anti-CD38 monoclonal antibody, such as Darzalex (daratumumab), or isatuximab.
Initial results from the study have already shown that 21% of the quad-refractory patients and 20% of the penta-refractory patients responded to treatment, which consisted of 80 mg oral selinexor combined with 20 mg dexamethasone, both given twice weekly in each four-week cycles.
Since no other therapy had previously shown responses in penta-refractory multiple myeloma, Karyopharm expanded the STORM study to include 120 additional penta-refractory myeloma patients.
Now, Karyopharm announced top-line results of this second part of the STORM study.
Among patients with penta-refractory myeloma, 25.4% responded to treatment, including two complete responses and 29 partial or very good partial responses. The median duration of response, a key secondary goal, was 4.4 months.
The safety profile of oral selinexor was consistent with that from Part 1 of this study, and other previous studies. The most common adverse events were nausea, vomiting, reduced appetite, and fatigue, and were all manageable, according to the company.
“Penta-refractory myeloma is an area of true unmet medical need as these patients have continued to progress despite receiving available therapies,” Sharon Shacham, PhD, Karyopharm’s founder, president, and chief scientific officer, said in a press release.
“We are fully committed to bringing this new, orally administered potential treatment option to patients who have no other therapy options of proven benefit,” Shacham added.
Karyopharm plans to present detailed results of the STORM study at an upcoming medical oncology meeting.
With these positive results, along with the FDA recently granting fast track designation to selinexor for the treatment of heavily treated multiple myeloma, Karyopharm will request an expedited FDA review in an effort to make the treatment more readily available for these patients.
The company also intends to seek regulatory approval in Europe from the European Medicines Agency in early 2019.