Safety and anti-tumor activity of a novel aCD25 Treg depleter RG6292 as a single agent and in combination with atezolizumab in patients with solid tumors
- Author(s)
- Gambardella, V; Ong, M; Rodriguez-Ruiz, ME; Machiels, JP; Sanmamed, MF; Galvao, V; Spreafico, A; Renouf, DJ; Luen, SJ; Galot, R; Doger de Speville, B; Calvo, E; Naing, A; Curdt, S; Kolben, TM; Rossmann, E; Tanos, T; Smart, K; Amann, M; Xie, Y; Xu, L; Gomez Alcaide, E; Städler, N; Justies, N; Boetsch, C; Karanikas, V; Schnetzler, G; Rohrberg, KS;
- Details
- Publication Year 2025-02-21,Volume 5,Issue #3,Page 422-432
- Journal Title
- Cancer Research Communications
- Publication Type
- Research article
- Abstract
- PURPOSE: Therapeutic depletion of immunosuppressive regulatory T cells (Tregs) may overcome resistance to cancer immunotherapies. RG6292 is an anti-CD25 antibody that preferentially depletes Tregs while preserving effector T cell functions in preclinical models. The safety, pharmacokinetics, pharmacodynamics, and anti-tumor efficacy of selective Treg depletion by RG6292 administered as monotherapy or in combination with atezolizumab was evaluated in two Phase I studies. MATERIALS AND METHODS: Adult patients with advanced solid tumors were administered intravenous RG6292 given every 3 weeks (Q3W) alone (Study 1: NCT04158583, N=76) or with 1200 mg atezolizumab Q3W (Study 2: NCT04642365, N=49). Both studies included dose escalation and expansion parts to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (R2PD). RESULTS: RG6292 was well-tolerated. Pruritus and rash were most frequent AEs and were manageable with supportive treatment. Serum RG6292 levels increased dose-proportionally, independent of atezolizumab combination. RG6292 induced a sustained dose-dependent depletion of peripheral Tregs with no apparent effect on other immune cells. Evidence of intratumoral Treg cell reduction (≥50% vs baseline) was observed at RG6292 doses of 35 to 100 mg. The MTD was 165 mg Q3W and the RP2D was proposed as 70 mg Q3W. Objective responses were limited to three partial responses in patients receiving RG6292 combined with atezolizumab. CONCLUSIONS: RG6292 induced a dose-dependent peripheral blood and measurable intratumoral Treg depletion in concordance with the proposed mode of action; however, clinical efficacy as single agent or combined with atezolizumab was insufficient to warrant further exploration in this population.
- Publisher
- American Association for Cancer Research
- Department(s)
- Medical Oncology
- Publisher's Version
- https://doi.org/10.1158/2767-9764.Crc-24-0638
- Open Access at Publisher's Site
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Creation Date: 2025-03-18 06:23:41
Last Modified: 2025-03-18 06:24:11