AACR 2017 | Poster CT132/13 – A phase IIb randomized study (SADAL) of selinexor achieves durable responses in GCB & Non-GCB subtypes of relapsed/refractory Diffuse Large B-Cell Lymphoma

At the American Association for Cancer Research (AACR) annual meeting in Washington, DC, USA, on Tuesday 4^th April, a poster session titled “Phase I-III Clinical Trials and Pediatric Clinical Trials” took place.

One of the posters on display (CT132 / 13) was titled “A Phase 2b randomized study of selinexor in patients with relapsed/refractory Diffuse Large B-Cell Lymphoma (DLBCL) demonstrates durable responses in both GCB & Non-GCB subtypes” by Marie Maerevoet from Institut Jules Bordet, Brussels, Belgium, and colleagues.

In this phase IIb trial (SADAL), R/R DLBCL patients were randomized to receive 60mg or 100mg of selinexor twice weekly (8 doses) per 28-day cycle. Additionally, patients were grouped by the subtype of their DLBCL (GCB or non-GCB). The primary objectives are to determine the ORR, and safety of 60mg compared to 100mg doses.

Key Highlights:

• In total, 67 pts enrolled (n = 33 at 60mg; n = 34 at 100mg) enrolled
• The most common related AEs across both dosing groups (grade 1/2) = nausea (46%), anorexia (43%), vomiting (36%), and fatigue (34%)
• Frequent grade 3/4 AEs = thrombocytopenia (39%), fatigue (18%), neutropenia (16%), and anemia (10%)
  • These were managed with dose interruption/reduction, platelet stimulators, and/or standard supportive care
• Grade 3/4 fatigue was higher in 100mg arm (13%) vs the 60mg arm (4%)
• Grade 3/4 thrombocytopenia was higher in 100mg arm (22%) vs the 60mg arm (16%)
• Among 65 evaluable pts, ORR = 21.5%
• Responders had a median of 3 prior treatment regimens
• CR = 12.3% (n = 8); PR = 9.2% (n = 6)
• Remain on treatment = 9 responders, including 7 CRs
• Median time on study for CR is 8.8+ months
• ORR by subtype: GCB = 23.5%; non-GCB = 19.3%
• ORR was higher in 60mg arm (26.4%) vs 100 mg arm (16.1%), potentially because of better tolerability and less time without drug exposure

In conclusion, monotherapy with selinexor demonstrates anti-cancer activity in R/R DLBCL patients including those with GCB subtype. Dosing at 60mg twice weekly was tolerated better than 100mg twice weekly, with less interruptions to dosing due to toxicity and a trend towards higher response rates. Moreover, durable objective responses were achieved with selinexor, which the authors hypothesize may be “associated with clinical benefit.”