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Preliminary Evidence Of Anti Tumor Activity Of Selinexor (KPT-330) In a Phase I Trial Ofa First-In-Class Oral Selective Inhibitor Of Nuclear Export (SINE) In Patients (pts) With Relapsed / Refractory Non Hodgkin’s Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL)

Kuruvilla J,Gutierrez M,Shah B,ET AL.

Key Points:

Exportin 1 renders Tumor Suppressor Proteins non-functional.
Selinexor an oral SINE XPO1 antagonist.
18NHL/CLL pts with median age 66.5yrs
ECOG PS 0/1: 8/10
Median number of regimens: 4.5 [range 2-11].
KPT-330 across 6 dose levels (3 to 30 mg/m2).
No clinically significant toxicities or major organ dysfunction.
Maximum tolerated dose not reached.
Selinexor induced tumor shrinkage/disease stabilization in 80%. of pts.
20% of pts had clinical progression.
One patient with Richter's transformation, refractory to chemotherapy and ibrutinib: rapid 60% reduction in lymph nodes in Cycle 1, referred for transplantation.
DLBCL pt failed R-CHOP and BMT achieved a near CR (93% tumor shrinkage).

Implications:

Oral Selinexor: well tolerated medication; induced tumor shrinkage in heavily pretreated.

Additional Comments:

Phase 1 study, maximum tolerated dose not achieved.
Well tolerated.
Very small number for clinical implication.
Potential in refractory patients.
Patient with ibrutinib refractory CLL with Ritcher's transformation responded.

View the original abstract on the ASH website.