Background: Malignant melanoma is the most common form of oral cancer in canines with a median survival of 3 months for dogs with stage III or IV disease. Currently, there are limited effective systemic treatment options for these patients with advanced disease. We have developed an anchored immunotherapy approach in which canine interleukin-12 is stably linked to aluminum hydroxide (cANK-101). The anchored IL-12 forms a stable, functional depot of IL-12 and is expected to increase therapeutic responses with limited systemic toxicity. We report the preliminary results of an exploratory Phase I study of cANK-101 in dogs with advanced melanoma. Methods: The clinical study was approved by the University of Illinois IACUC, conducted at the College of Veterinary Medicine, and all pet owners provided written informed consent. The primary objective of the trial was to determine the safety and tolerability of cANK-101 in dogs with advanced melanoma. A standard 3+3 dose-escalation design was used with three dose levels (1, 3, and 10 µg/kg) cANK-101 given by intratumoral injection every three weeks for 4 cycles. In the absence of overt clinical progression, dogs were allowed to receive a second course of four cycles. Dogs were monitored for adverse events via VCOG-CTCAE and clinical responses were measured using RECISTv1.1. Serum was collected for pharmacokinetic (PK) and immunogenicity analyses. In addition, serial tumor biopsy and lymph node cytology were performed. Serum cytokines were assayed via ELISA while immunophenotyping of PBMC and lymph node aspirates were assessed by flow cytometry. Tumor-infiltrating lymphocyte (TIL) analysis was performed by immunohistochemistry (IHC) and gene expression profiling (Nanostring). Descriptive statistics were used for analyses. Results: As of November 16, 2022, 8 dogs have been enrolled and all dogs remain on treatment. Thirteen adverse events have been reported in 6 dogs, all being grade 1. However, only two are considered related to the study drug (tumor site inflammation and pain). Treatment was associated with increases in serum IFNγ and IL-10, as well as increases in peripheral CD4+ T and CD21+ T cells. Additional data on PK analyses, anti-drug antibody levels, gene expression, and clinical responses will be presented. Conclusions: Thus far, cANK-101 appears to be safe and tolerable in dogs with advanced melanoma. Data from this trial will help inform human clinical trials and may represent a new therapeutic option for dogs with advanced melanoma and perhaps other solid tumors. Our experience further suggests that companion animal trials could serve as relevant translational models for early immuno-oncology drug development. Citation Format: Matheus Moreno Passos Barbosa, Angel J. Lopez, Rachel Uyehara, Rebecca L. Kamerer, Michael Schmidt, Sailaja Battula, Howard L. Kaufman, Timothy M. Fan. Preliminary results of an exploratory phase I clinical trial of anchored canine interleukin-12 (cANK-101) in dogs with advanced oral malignant melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6347.

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