1.Proof-of-concept study of the caninized anti-canine programmed death 1antibody in dogs with advanced non-oral malignant melanoma solid tumors
Masaya IGASE ; Sakuya INANAGA ; Shoma NISHIBORI ; Kazuhito ITAMOTO ; Hiroshi SUNAHARA ; Yuki NEMOTO ; Kenji TANI ; Hiro HORIKIRIZONO ; Munekazu NAKAICHI ; Kenji BABA ; Satoshi KAMBAYASHI ; Masaru OKUDA ; Yusuke SAKAI ; Masashi SAKURAI ; Masahiro KATO ; Toshihiro TSUKUI ; Takuya MIZUNO
Journal of Veterinary Science 2024;25(1):e15-
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One dog was withdrawn, and thirty-seven dogs were evaluated for the safety and efficacy of ca-4F12-E6.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.
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