title: Phase 1 Dose-Escalation Study with LEC/chTNT-3 and Toceranib Phosphate (Palladia®) in Dogs with Spontaneous Malignancies.
abstract: OBJECTIVE
  LEC chemokine promotes TH1 responses and recruits immune cells to inflammatory sites. By linking LEC to an antibody targeting tumor necrosis, LEC/chTNT-3 can be used for the immunotherapeutic treatment of tumors. The primary objective of this study was to determine the safety profile of LEC/chTNT-3 and toceranib phosphate (Palladia®) combination therapy in dogs with spontaneous malignancies. Secondary purpose was to determine objective responses to treatment.
  
  
  METHODS
  Twenty-three dogs with cancer were enrolled, covering nine different malignancies. In this dose escalation study, dogs received LEC/chTNT-3 for five days, and toceranib every 48 hours for the remainder of the study. Dogs received physical exams, chemistry panel, urinalysis, and complete blood counts on days 0, 10, 28 of the study, and every 6-8 weeks thereafter.
  
  
  RESULTS
  Lethargy was noted in 13% dogs. There were no statistical differences in the prevalence of anorexia, diarrhea, thrombocytopenia, renal toxicity, or hepatic toxicity before or during the study. There were trends in increases in the prevalence of vomiting, lymphopenia, and neutropenia (all grade 2 or lower, p=0.07) over the initial 28 days of the study. By day 28, 10% of dogs had partial responses, 58% had stable disease, and 32% had progressive disease.
  
  
  CONCLUSIONS
  LEC/chTNT-3 and toceranib were well tolerated. This combination therapy showed some biological activity against a variety of cancers at a low dose and short duration of LEC/chTNT-3 administration.
authors.affiliation: Department of Pathology, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA.
authors.forename: Julie K
authors.initials: JK
authors.lastname: Jang
authors.affiliation: Veterinary Centers of America West Los Angeles Animal Hospital, Los Angeles, CA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Chretin
authors.affiliation: Veterinary Centers of America West Los Angeles Animal Hospital, Los Angeles, CA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Bruyette
authors.affiliation: Department of Pathology, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA.
authors.forename: Peisheng
authors.initials: P
authors.lastname: Hu
authors.affiliation: Department of Pathology, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA.
authors.forename: Alan L
authors.initials: AL
authors.lastname: Epstein
keywords: Canine; Chemokine; Immunocytokine; Immunotherapy; LEC; Safety; TNT antibody; Toceranib