A PHASE 2B STUDY OF SELINEXOR IN PATIENTS WITH RELAPSED/REFRACTORY (R/R) DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL)

Abstract

Introduction: Patients (pts) with R/R DLBCL who have received at least 2 lines of therapy, including pts who have progressed post stem cell transplantation (SCT) or who are not candidates for SCT, have limited treatment options. Active novel therapies with different mechanisms of actions are needed to improve the survival of these pts. Selinexor, a selective oral XPO1 inhibitor, leads to nuclear accumulation and activation of tumor suppressor proteins (e.g., p53, p21, and IkB), and reductions in c-Myc and Bcl-2 oncogenes. Single agent selinexor in heavily treated DLBCL demonstrated an overall response rate (ORR) of 25.6% with complete response (CR) in 9.3%, in a phase 1 study. To confirm these findings, a phase 2b study of selinexor was initiated. Methods: This is a multicenter, open-label study in pts with R/R DLBCL who have received 2-5 lines of prior therapy. Pts may have progressed post SCT or are not candidates for SCT. Pts were stratified by subtype (germinal center B-cell [GCB] or non-GCB) and treated with 60 mg selinexor twice weekly per 28-day cycle. The primary endpoint was ORR. Secondary endpoints included duration of response (DOR) and assessment of safety. Disease response was assessed by an Independent Central Radiological Review (ICRR), using the Lugano Classification. Results: 129 pts were enrolled (76 M, 53 F). Median age was 67 years (54% of pts >65 years). Median number of prior therapies was 2 (range 1-6), 34% of pts received #8805;3 prior therapies, and 31% of pts had prior SCT. Two pts did not meet eligibility requirements and were excluded from the analysis. Treatment-related serious adverse events (SAEs) were reported in 21% of pts. The most frequently reported treatment-related AEs (Grades 3, 4) included: nausea (6%, 0%), thrombocytopenia (24%, 13%), fatigue (9%, 0%), anorexia (3%, 0%), and anemia (13%, 1%). Of the 85.8% pts who discontinued treatment, the majority were due to progressive disease and 9.3% were due to AEs. The ICRR determined ORR was 27.6% (14 CRs and 21 partial responses). The ORR was 32.2% for GCB and 20.6% for non-GCB subtypes. Median time to response was 57 days (range 47-115 days) and the median DOR was 8.4 months; pts with a CR had a median DOR of 13.4 months. Median progression free survival was 3.6 months. The median overall survival (OS) was 9.1 months. Median OS in pts ≥partial response was 29.7 months which was significantly longer than the 5.0 months observed in pts ≤stable disease (p<0.0001) [Figure 1]. Conclusion: Single agent, oral selinexor demonstrated deep and durable responses in R/R DLBCL (ORR of 27.6% and DOR of 8.4 months). No new safety signals were identified; AEs were managed with dose modification and/or supportive care. Clinical benefit was observed across both GCB and non-GCB subtypes. These results underscore the potential of selinexor as a novel therapy for R/R DLBCL.