Abstract CT206: EVT801, a novel selective VEGFR-3 inhibitor targeting tumor angiogenesis, started enrollment for its phase I first-in-human study

Abstract

Abstract Introduction: EVT801 is a highly selective, orally available VEGFR3 inhibitor that strongly inhibits angiogenesis without inducing hypoxia, considered one of the main causes of cancer-associated immunosuppression. EVT801 has shown compelling single agent efficacy in multiple in vivo models. In addition, combination of EVT801 and Immune Checkpoint Therapy (ICT) agents shows additive effects, and thus holds promise for combination treatment without induction of hypoxia-induced-immunosuppression. A phase I clinical trial is underway. Methods: The phase I trial will consist of two sequential stages. During the first stage, EVT801 will be administered to patients with advanced solid tumors in a multiple ascending dose study using an accelerated 3+3 design (1 patient per dose until grade 2 toxicities are observed) in up to 48 patients in 8 dose levels. The primary objective is to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Stage 2 will focus on validation of this RP2D in two 6-patient cohorts diagnosed with soft tissue sarcoma or renal cell carcinoma. These patients will participate in intensive analyses involving several biomarkers to better understand the pharmacological activity of the drug. A potential third stage, consisting of a multiple ascending dose evaluation of the combination of EVT801 with immuno-oncology drugs, may be added to the ongoing trial, pending further technical discussions with physicians and regulators. In addition to conventional measures of safety, tolerability, efficacy, and pharmacokinetics, the phase I study will employ a rich suite of histological, immunological, and radiological biomarkers to provide early insights into the activity of EVT801. Citation Format: Carlos Gomez roca, Philippe Cassier, Marie Mandron, Myriam Estrabaut, Nathalie Delesque-Touchard, Adam C. Smith, Amy Klawitter, Leesa Gentry, Pierre Fons, Michael R. Paillasse, Lise Davenne, Michael Fitzgerald, James Garner, Jean-Pierre Delord. EVT801, a novel selective VEGFR-3 inhibitor targeting tumor angiogenesis, started enrollment for its phase I first-in-human study [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 CT206.