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

BMC Vet Res. 2018 Aug 24;14(1):250. doi: 10.1186/s12917-018-1587-9.

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.

Keywords: Anti-tumor agent; Clinical trial; Non-Hodgkin lymphoma; Nuclear export.

Publication types

  • Clinical Trial, Phase II

MeSH terms

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

Substances

  • Acrylamides
  • Antineoplastic Agents
  • Hydrazines
  • verdinexor