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

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.

altmetric score

  • 2.85

author list (cited authors)

  • Sadowski, A. R., Gardner, H. L., Borgatti, A., Wilson, H., Vail, D. M., Lachowicz, J., ... London, C. A.

citation count

  • 9

publication date

  • August 2018