Abstract 934: Use of real-world data of dogs with cancer to drive drug development strategy and inform human clinical trials
Authors: Schwalbach Chase , Rodrigues Lucas , Harvey Garrett , Girimonte Dorothy , Post Gerald , Lambert Lindsay , Miller Aubrey , Hull Abigail , Lopes Christina , White Michelle E. 
Published: April 2023

Abstract
In recent years, clinico-genomic databases integrating real-world data (RWD) from electronic health records and tumor genomic profiles have been used to expedite development of new, precision medicine therapies for cancer treatment. Clinical trials in humans for new targeted therapies are often limited to approved use only as second- or third-line chemotherapies, complicating the ability to make conclusions about the efficacy of the drug alone. Pre-clinical trials in murine models with induced or xenograft tumors often fail to predict response in the intended human population. Several studies have qualified spontaneous tumors in dogs as important models for human cancers. Tumors in dogs are highly similar to human cancers histologically, genetically, molecularly and clinically, which provides an opportunity to investigate biomarkers and outcomes. Canine cancers progress over an accelerated timeline compared to human cancers due to several factors including differences in expected lifespan. Additionally, more flexibility exists in treatment options for canine cancers than in the more tightly regulated and standardized human care model. These key similarities and differences make dogs a powerful model for cancer research including interrogating the clinical benefit of new and existing cancer therapies. Over 3,500 dogs have enrolled into the FidoCure® Precision Medicine Platform. Our current, ongoing studies use clinico-genomic data from dogs with cancer including those with naïve or early stage tumors as a tool to evaluate and inform clinical response to small-molecule targeted therapies, and our model allows for expansion into trials for additional, diverse therapy types. Using the FidoCure® Next-Generation Sequencing (NGS) panel, molecular targets are identified in canine tumors for treatment regimens with one or combinations of 12 small molecules approved for use in humans. Clinical information and outcomes data from participating dogs is collected and analyzed. In an unbiased, AI-driven analysis of our dataset, several significant prognostic findings with translational relevance included association of TP53 mutations with worse prognosis (OS HR 1.48, P&lt;0.01) across 14 canine tumor types. Conversely, ATM and KIT mutations were associated with better prognosis (OS HR) of 0.51 and 0.43, respectively (P=0.01, P=0.02). We are now developing a tool called Fetch for real-time exploration of our dataset for use by external partners including clinicians and biopharmaceutical collaborators to visualize correlations between single or combinations of factors such as cancer type, breed, gene mutated, and treatment regimen with survival outcomes in our canine patient population. This tool can accelerate R&D by making real-time, real-world data on thousands of dogs with translationally relevant disease available to clinicians and researchers looking to advance cancer treatment.
Citation Format: Chase Schwalbach, Lucas Rodrigues, Garrett Harvey, Dorothy Girimonte, Gerald Post, Lindsay Lambert, Aubrey Miller, Abigail Hull, Christina Lopes, Michelle E. White. Use of real-world data of dogs with cancer to drive drug development strategy and inform human clinical trials [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 934.