Photo by Esther Dyson
An excess of sepsis cases has prompted dose reductions in a phase 2 trial of selinexor in older patients with relapsed/refractory acute myeloid leukemia (AML).
For this study, known as SOPRA, researchers are comparing selinexor to physician’s choice of treatment in AML patients age 60 and older.
There have only been 8 cases of sepsis in the selinexor arm thus far, but this is more than observed in the physician’s
choice arm.
So the company developing selinexor, Karyopharm Therapeutics Inc., said it has reduced the selinexor dose used in this study.
The company decided to reduce the dose from 55 mg/m2 to a fixed dose of 60 mg, which corresponds to approximately 35 mg/m2. Dosing will remain twice weekly.
The change was implemented based on ongoing safety and tolerability evaluations in the SOPRA study, as well as maturing data from AML patients in the phase 1, first-in-human trial of selinexor.
The SOPRA study uses a 2 to 1 randomization of AML patients to selinexor or physician’s choice and, therefore, approximately twice as many cases of sepsis would be expected on the selinexor arm compared with the physician’s choice arm.
As of the end of July 2015, there have been 8 reports of sepsis in 7 patients receiving selinexor at 55 mg/m2, compared with 2 reports of sepsis in 2 patients receiving physician’s choice.
Karyopharm pointed out that these numbers are small, and sepsis is often observed in patients with AML, but the incidence of sepsis appears to be higher in the patients receiving selinexor.
In addition, the company noted an apparent increase in the incidence of sepsis in patients with relapsed or refractory AML receiving high doses of selinexor twice weekly in the phase 1 trial of patients with hematologic malignancies.
Karyopharm said selinexor doses of 60 mg twice weekly do not appear to be associated with any increase in sepsis or other infection-related events in patients with hematologic malignancies or solid tumors.
In addition, most patients with AML in the phase 1 study who showed a response to selinexor, including complete responses, received the drug at doses of approximately 60 mg or lower.
As a result of the change in dose, the SOPRA study will now have an interim assessment in mid-2016.
Karyopharm is actively enrolling patients in the SOPRA study, as well as a study of selinexor in patients with relapsed/refractory diffuse large B-cell lymphoma (SADAL trial), and a study of the drug in patients with Richter’s transformation (SIRRT trial).
Preliminary top-line data from all 3 studies are anticipated in the fourth quarter of 2016.
The company has also initiated a single-arm trial of selinexor plus dexamethasone in patients with multiple myeloma (STORM trial), which will initially include 80 patients. Preliminary top-line data from this study are anticipated in mid-2016.
