Phase II study of the oral selective inhibitor of nuclear export (SINE) KPT-335 (verdinexor) in dogs with lymphoma

• Published in: BMC veterinary research Vol. 14; no. 1; p. 250
• Main Authors: Sadowski, Abbey R, Gardner, Heather L, Borgatti, Antonella, Wilson, Heather, Vail, David M, Lachowicz, Joshua, Manley, Christina, Turner, Avenelle, Klein, Mary K, Waite, Angharad, Sahora, Alexandra, London, Cheryl A
• Format: Journal Article
• Language: English
• Published: England BioMed Central 24.08.2018; BMC
• Subjects: Anorexia; Anti-tumor agent; Antitumor agents; Bioavailability; Biological activity; Cancer; Cell cycle; Clinical trial; Clinical trials; Dogs; Exports; Leukemia; Lymphocytes B; Lymphocytes T; Lymphoma; Medical prognosis; Non-Hodgkin lymphoma; Nuclear engineering; Nuclear export; Nuclear safety; Nuclear transport; Oncology; Oral administration; Prednisone; Proteins; Studies; T-cell lymphoma; Tumors; Non-Hodgkin lymphoma; Anti-tumor agent; Clinical trial; Nuclear export
• ISSN: 1746-6148; 1746-6148
• DOI: 10.1186/s12917-018-1587-9

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. 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. 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.