FDA Places Partial Clinical Hold on Selinexor for Multiple Myeloma

The FDA placed clinical trials of selinexor on a partial hold, halting enrollment of new patients in the studies but allowing those who have experienced stable disease or better to continue treatment. The clinical hold is due to incomplete information in the existing version of the investigator’s brochure, including an incomplete list of serious AEs associated with selinexor. Karyopharm Therapeutics, the manufacturer of selinexor, said it submitted the revised informed consent documents to the FDA.

Phase II results of the STORM trial were presented at the 2016 ASH Annual Meeting and demonstrated an overall clinical benefit rate (defined as an overall response rate + molecular response) of 32 percent for all patients.

The study included 78 patients with MM who received a median of seven prior therapies and were refractory to bortezomib, carfilzomib, lenalidomide, and pomalidomide (“quad-refractory”; n=48); a subset of 30 patients was refractory to an investigational anti-CD38 antibody (either daratumumab or isatuximab; “penta-refractory”). Patients were treated with selinexor 80 mg (twice a week) for six or eight doses per 28-day cycle and dexamethasone 20 mg (twice a week).

The ORR (primary endpoint; including PR and very-good PR) was 21 percent for all patients, 21 percent in the quad-refractory group, and 20 percent in the penta-refractory group.

The most common treatment-related hematologic AEs included thrombocytopenia (72%), anemia (48%), and neutropenia (29%), whereas the most common non-hematologic AEs included nausea (72%), fatigue (62%), anorexia (49%), vomiting (43%), asymptomatic hyponatremia (42%), diarrhea (42%), and weight loss (33%). There was one case of febrile neutropenia (1%) and one case of clinically significant bleeding related to thrombocytopenia (1%).

Seventy patients discontinued therapy because of progressive disease (73%), AEs (17%), or physician or patient preference (1%). Six deaths were reported, one of which was deemed related to selinexor.

Source: Karyopharm Therapeutics news release, March 10, 2017.