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

Abstract

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.

• Authors: Abbey R Sadowski, Heather L Gardner, Antonella Borgatti, Heather Wilson, David M Vail, Joshua Lachowicz, Christina Manley, Avenelle Turner, Mary K Klein, Angharad Waite, Alexandra Sahora, Cheryl A London
• Journal: BMC veterinary research (BMC Vet Res) Vol. 14 Issue 1 Pg. 250 (Aug 24 2018) ISSN: 1746-6148 [Electronic] England
• PMID: 30143046 (Publication Type: Clinical Trial, Phase II, Journal Article)

Chemical References

• Acrylamides
• Antineoplastic Agents
• Hydrazines
• verdinexor

Topics

• Acrylamides (administration & dosage, adverse effects, therapeutic use)
• Active Transport, Cell Nucleus (drug effects)
• Administration, Oral
• Animals
• Anorexia
• Antineoplastic Agents (administration & dosage, adverse effects, therapeutic use)
• Dogs
• Dose-Response Relationship, Drug
• Female
• Hydrazines (administration & dosage, adverse effects, therapeutic use)
• Lymphoma (drug therapy, veterinary)
• Male