FDA approves selinexor for the treatment of patients with R/R DLBCL

On June 22, 2020, the U.S. Food and Drug Administration granted approval to selinexor for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after ≥ 2 prior lines of systemic therapy.¹

The accelerated approval of this first-in-class, oral, selective inhibitor of nuclear export (SINE) compound was based on results from the phase IIb SADAL study (NCT02227251). The FDA’s Accelerated Approval program granted approval based on response rates, and continued approval for the R/R DLBCL indication may depend on verification and description of clinical benefit in confirmatory trials.

The SADAL trial evaluated 134 patients with R/R DLBCL who had a median of two prior lines of systemic therapies (range, 1–5). Selinexor was administered orally at a fixed dose of 60 mg, twice weekly, for a 4-week cycle. The primary endpoint of overall response rate was met: the overall response rate was 29%, including a complete response rate of 13% and partial response rate of 16%. A key secondary endpoint was the median duration of response; 56% of patients maintained a response at 3 months, 38% at 6 months, and 15% at 12 months.

All 134 patients were included in the safety analyses. The most common treatment-related adverse events were cytopenias, gastrointestinal symptoms, and constitutional symptoms. These were managed with dose alterations and/or standard supportive care. The most common non-hematologic adverse events were mostly Grade 1 and 2 events, and included fatigue (63%), nausea (57%), decreased appetite (37%), and diarrhea (37%). Laboratory abnormalities of Grade 3 and 4 that occurred in ≥ 15% of patients were thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. Laboratory abnormalities of Grade 4 that occurred in ≥ 5% of patients included thrombocytopenia (18%), lymphopenia (5%), and neutropenia (9%).

As part of the FDA Accelerated Approval process, an additional trial—the XPORT-DLBCL-030 trial (NCT04442022)—could be used as the confirmatory study for evaluating selinexor in DLBCL. This study aims to assess the efficacy of selinexor vs placebo combined with the standard backbone immunochemotherapy of rituximab–gemcitabine–dexamethasone–platinum (R-GDP) in patients with R/R DLBCL. This study is anticipated to begin by the end of 2020.

Earlier on in the year, the FDA accepted the supplemental new drug application filing for selinexor as a treatment for R/R DLBCL; click here to read about it. Selinexor has also previously received both orphan drug and Fast Track designations from the FDA for the treatment of patients with relapsed or refractory DLBCL.