Proof-of-concept study of the caninized anti-canine programmed death 1 antibody in dogs with advanced non-oral malignant melanoma solid tumors

Background: The anti -programmed death 1 (PD -1) antibody has led to durable clinical responses in a wide variety of human tumors. We have previously developed the caninized anti -canine PD -1 antibody (ca -4F12 -E6) and evaluated its therapeutic properties in dogs with advance -staged oral malignant melanoma (OMM), however, their therapeutic effects on other types of canine tumors remain unclear. Objective: The present clinical study was carried out to evaluate the safety profile and clinical efficacy of ca -4F12 -E6 in dogs with advanced solid tumors except for OMM. Methods: Thirty-eight dogs with non-OMM solid tumors were enrolled prospectively and treated with ca -4F12 -E6 at 3 mg/kg every 2 weeks of each 10 -week treatment cycle. Adverse events (AEs) and treatment efficacy were graded based on the criteria established by the Veterinary Cooperative Oncology Group. Results: One dog was withdrawn, and thirty-seven dogs were evaluated for the safety and efficacy of ca -4F12 -E6. Treatment -related AEs of any grade occurred in 13 out of 37 cases (35.1%). Two dogs with sterile nodular panniculitis and one with myasthenia gravis and hypothyroidism were suspected of immune -related AEs. In 30 out of 37 dogs that had target tumor lesions, the overall response and clinical benefit rates were 6.9% and 27.6%, respectively. The median progression -free survival and overall survival time were 70 days and 215 days, respectively. Conclusions: The present study demonstrated that ca -4F12 -E6 was well -tolerated in nonOMM dogs, with a small number of cases showing objective responses. This provides evidence supporting large-scale clinical trials of anti -PD -1 antibody therapy in dogs.