Antitumor Activity of KTN0158 in Canine Mast Cell Tumor Treatment: Insights from a Humanized Anti-KIT Monoclonal Antibody Study

KTN0158 is a newly developed humanized anti-KIT IgG1 monoclonal antibody that has a strong binding capacity to the KIT protein across various species, including humans. This antibody has shown significant inhibitory effects on both the standard and some mutated forms of KIT in laboratory settings and has been observed to influence the function and survival of mast cells in dogs. A clinical trial involving dogs with naturally occurring mast cell tumors was undertaken to assess the safety, biological activity, and the pharmacokinetic and pharmacodynamic profile of KTN0158.

In this phase 1 clinical trial, twelve dogs with measurable mast cell tumors were included. The trial was open-label and involved a dose-escalating approach with three different dose levels and two administration schedules. Tumor biopsies and blood samples were collected at various points before and after treatment for pharmacokinetic and pharmacodynamic analysis. The dogs were examined weekly for clinical toxicities and response to treatment. Adverse events were recorded and graded according to established criteria for dogs. The efficacy of the treatment was determined based on the established RECIST criteria for solid tumors in dogs.

The study found that all twelve dogs treated with KTN0158 at the tested doses showed clinical benefits, with partial responses in five dogs and stable disease in seven. Post-study, eleven dogs underwent surgery to remove the tumors, and histopathology revealed the absence of neoplastic mast cells in samples from two dogs and three lymph nodes from three dogs that were initially classified as metastatic. The most common side effects were reversible hematologic changes, with more significant toxicities observed at the higher dose of 30 mg/kg. The ongoing evaluation of pharmacokinetic and pharmacodynamic biomarkers is expected to provide further insights.

The study concluded that KTN0158 at doses of 1 and 10 mg/kg showed an acceptable safety profile and biological activity in a large animal model of KIT-driven malignancy. The observed responses in tumors with and without activating KIT mutations suggest potential clinical benefits for patients with GIST and other KIT-driven tumors, prompting plans for human clinical studies.