Abstract CT118: Preliminary data from Phase I first-in-human study of EOS884448, a novel potent anti-TIGIT antibody, monotherapy shows favorable tolerability profile and early signsof clinical activity in immune-resistant advanced cancers
Authors: Van den Mooter Tom F.A. , Migeotte Ariane , Jungels Christiane , Delafontaine Brant R. , Nguyen Thi Lien-Anh , Warot Servane , Truong Clarise , De Henau Olivier , Driessens Gregory , Lager Joanne , Rottey Sylvie , Machiels Jean-Pascal 
Published: July 2021

Abstract
TIGIT is an immunosuppressive mediator expressed by various immune cells in the microenvironment of most tumors. In preclinical models, targeting TIGIT with an FCγR-engaging antibody promotes an anti-tumor immune response. EOS884448 is designed to be a potent and highly selective fully human antagonist IgG1 antibody targeting TIGIT. This multicenter, first-in-human Phase I/IIa clinical trial (NCT04335253) is assessing the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of EOS884448 monotherapy in subjects with advanced solid tumors. PD assessments were performed in peripheral blood with simultaneous determination of plasma PK. This report describes a preliminary analysis of the Phase I dose escalation part of the ongoing study with a data cut-off of December 15, 2020. Twenty-two adult participants with advanced solid malignancies have been treated with EOS884448 monotherapy. All subjects had at least 1 prior anti-cancer therapy. Cohorts of at least 3 participants were evaluated at doses of 20, 70, 200, 700 mg Q2W and 1400 mg Q4W administration. PK analyses indicated a dose-proportional increase of EOS884448 plasma exposures. PD evaluations revealed prolonged and maintained TIGIT occupancy over the dosing interval that correlated with significant depletion of suppressive Treg cells (CD4+CD25+CD127low) beginning at the lowest dose level. In terms of safety, 54 adverse events attributed to the investigational treatment were reported, 16 of which were considered immune-related. The most common (&gt;10%) related adverse events (AEs) included Grade 1-2 rash and pruritus. No drug-related Grade 3-4 AEs and no dose-limiting toxicities were observed. Among the 20 patients who had at least one disease assessment, stable disease was observed in 8 participants, 4 of whom remain on therapy, and 1 partial response was observed in a patient with checkpoint inhibitor-refractory, BRAF-mutated melanoma. Overall, the early data from this Phase I trial show a manageable tolerability profile, a PK profile as expected for an IgG1 antibody, and evidence of immunomodulation with reductions in suppressive Treg cells beginning at the lowest dose tested. These observations correlate with early signs of clinical activity that will continue to be monitored in the ongoing trial. Further evaluation of EOS884448 as monotherapy and in combination with approved and investigational therapies is planned in both immune checkpoint-naïve and -refractory patients.
Citation Format: Tom F.A. Van den Mooter, Ariane Migeotte, Christiane Jungels, Brant R. Delafontaine, Thi Lien-Anh Nguyen, Servane Warot, Clarise Truong, Olivier De Henau, Gregory Driessens, Joanne Lager, Sylvie Rottey, Jean-Pascal Machiels. Preliminary data from Phase I first-in-human study of EOS884448, a novel potent anti-TIGIT antibody, monotherapy shows favorable tolerability profile and early signsof clinical activity in immune-resistant advanced cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT118.