Abstract ND08: Anti-CD25 Mab: Selective depletion of T-regulatory cells

Abstract

Abstract Tregs can suppress anti-tumour immune responses allowing for tumour growth. The negative prognostic impact of Tregs has been shown in several tumor settings. So far, Treg depletion has not been successful in patients, either because relevant Treg depletion was not achieved or because Teff cells have either been impacted or depleted as well. RG6292 has been optimised for ADCC selective depletion of cells with high CD25 density (Treg) and spares effector T cells by preserving IL-2-STAT5 signaling. RG6292 is currently tested in a Ph1 dose escalation study, and is given as monotherapy i.v. Q3W in adult patients with advanced solid tumors. 29 pts have been treated thus far at dose levels ranging from 0.3 mg to 35 mg. A dose dependent peripheral Treg depletion was observed as expected from RG6292 design and a significant flux of activated CD8+T cells as well as increase of PDL1 expression and intensity were observed in 3/3 patients in on-treatment biopsies taken 28 days after initiation of treatment. RG6292 at the doses tested was well tolerated in patients with advanced metastatic solid tumors and yielded encouraging PD effects consistent with its mechanism of action. Citation Format: Theresa Kolben. Anti-CD25 Mab: Selective depletion of T-regulatory cells [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 ND08.