Phase II study of the oral selective inhibitor of nuclear export (SINE) KPT-335 (verdinexor) in dogs with lymphoma.
BACKGROUND
Chemotherapeutic options for the treatment of canine lymphoma have not changed in several decades necessitating the identification of new therapeutics to improve patient outcome. KPT-335 (verdinexor) is a novel orally bioavailable selective inhibitor of nuclear export (SINE) that exhibited anti-tumor activity against non-Hodgkin lymphoma in a prior phase I study. The objective of this phase II study was to expand upon the initial findings and assess the activity and safety in a larger population of dogs with lymphoma.


RESULTS
Fifty-eight dogs with naïve or progressive B-cell and T-cell lymphoma were enrolled in this clinical trial. KPT-335 was administered orally in one of three dosing groups, based on the previously established biologically active dose of 1.5 mg/kg three times weekly. Treatment with single-agent, orally administered KPT-335 resulted in an objective response rate (ORR) of 37%, of which dogs with T-cell lymphoma had an ORR of 71%. KPT-335 was well tolerated in all dose groups with grade 1-2 anorexia being the most common adverse event. Anorexia was responsive to symptomatic and supportive medications, including prednisone.


CONCLUSIONS
These data demonstrate that KPT-335 has biologic activity in canine lymphoma, and support continued evaluation of SINE compounds such as KPT-335 in combination with standard chemotherapeutics in canine lymphoma.
['Sadowski|Abbey R|AR|', 'Gardner|Heather L|HL|', 'Borgatti|Antonella|A|', 'Wilson|Heather|H|', 'Vail|David M|DM|', 'Lachowicz|Joshua|J|', 'Manley|Christina|C|', 'Turner|Avenelle|A|', 'Klein|Mary K|MK|', 'Waite|Angharad|A|', 'Sahora|Alexandra|A|', 'London|Cheryl A|CA|http://orcid.org/0000-0001-8563-1490']
D000178:Acrylamides D021581:Active Transport, Cell Nucleus D000284:Administration, Oral D000818:Animals D000855:Anorexia D000970:Antineoplastic Agents D004285:Dogs D004305:Dose-Response Relationship, Drug D005260:Female D006834:Hydrazines D008223:Lymphoma D008297:Male
Nuclear export Non-Hodgkin lymphoma Clinical trial Anti-tumor agent