Abstract 3203: Cutting edge biomarkers strategy to provide early insights into activity of EVT-801, a novel selective VEGFR-3 inhibitor that targets tumor angiogenesis during the FIH clinical trial

Abstract

Abstract Introduction: EVT801 is a highly selective small molecule inhibitor of VEGFR3 and acts by inhibiting lymphangiogenesis and tumor angiogenesis in and around the tumor. It has shown compelling activity in a wide range of cancer models and is well-tolerated in preclinical toxicology studies. A phase I study is underway and will focus primarily on understanding the safety, tolerability, and pharmacokinetics of EVT801 across a range of doses. Methods: The first stage of the study is designed to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) for EVT801, with a second stage aiming to confirm RP2D in selected cancer patient populations. Clinical samples from these patients will be used to explore preliminary signals of clinical efficacy and investigate the biological activity of the drug using several biomarkers. Efficacy biomarkers will include imaging approaches (DCE-MRI and CEUS) to characterize tumor vascularization, as well as analysis of protein and mRNA quantification in on-treatment biopsies vs pre-treatment biopsies. Moreover, the relationship between activity of EVT801 and expression of key markers at protein and mRNA level will be investigated to potentially establish biomarkers for patient stratification and selection. Lastly, target engagement and pharmacodynamics effects will be investigated by immuno-monitoring as well as assessment of a defined set of proteins as markers of inflammation and angiogenesis as identified in preclinical in vivo models. We expect that these analyses will help to better understand the effects of the drug in human subjects and may also help to select the most responsive patients and provide early signs of clinical efficacy. Citation Format: Michael R. Paillasse, James Garner, Michael Fitzgerald, Lise Davenne, Pierre-Benoit Ancey, celine Poussereau-Pomie, Michael Esquerre, Gaelle Badet, Joel Tuyaret, Marie Mandron, Philippe Rochaix, Maha Ayyoub, Clara Maria Scarlata, Christine Ménétrier-Caux, Chrsitophe CAUX, Philippe Cassier, Jean-Pierre Delord, Carlos Gomez Roca, Pierre Fons. Cutting edge biomarkers strategy to provide early insights into activity of EVT-801, a novel selective VEGFR-3 inhibitor that targets tumor angiogenesis during the FIH clinical trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3203.