LAUSR

Background RG6292 is the first anti-human CD25 antibody developed to specifically deplete human Tregs while preserving IL-2R STAT5 signaling and Teff activity. Methods Patients with advanced/metastatic solid tumors and without standard treatment options were enrolled in dose escalation studies and received RG6292 i.v. Q3W as monotherapy (S1: NCT04158583) or in combination with atezolizumab 1200 mg Q3W (S2: NCT04642365) until disease progression or unacceptable toxicities to determine the maximum tolerated dose (MTD) and/or optimal biological dose, safety and preliminary clinical activity. DLT window was 4 weeks and dose increments were determined by a Bayesian-based continuous reassessment method (CRM) with overdose control. Adverse events (AEs) were graded by NCI CTCAE v5.0. Tumors were assessed by RECIST 1.1 every 8 weeks in the first year and then every 12 weeks. Results As of 27th May, 2022, 76 patients have been treated with RG6292 monotherapy (dose ranging from 0.3 - 165 mg). Six DLTs were reported, including rash, papular rash, rash macular-papular, AST elevation and ALT elevation. MTD is 165 mg. Seventy-five patients (99%) experienced at least one AE. The most common AEs were pruritus (32%), rash (29%) and fatigue (29%). Thirty-five patients (46%) experienced grade ≥ 3 AEs and 2 patients discontinued from study treatment due to AEs. Fourteen patients (18%) experienced grade ≥ 3 TRAEs. No AEs led to a fatal outcome. Median treatment duration was 43 days. Twenty-three patients have SD as best overall response. Forty-eight patients have been treated with RG6292 (dose ranging from 0.3 - 160 mg) in combination with atezolizumab. Two DLTs were reported, including immune system disorder and maculopapular rash. MTD has not been reached. Forty-seven patients (98%) experienced at least one AE. The most common AEs reported were pruritus (44%), rash (33%) and fatigue (33%). Twenty patients (42%) experienced grade ≥3 AEs and 2 patients discontinued from study treatment due to AEs. Five patients (10%) experienced grade ≥3 TRAEs. No AEs led to a fatal outcome. Median treatment duration was 54 days. Pruritus and rash were expected AEs and easily managed withtopical steroids or short course, low dose systemic steroids. Two patients have PR and 19 patients have SD as best overall response. Conclusion RG6292 is well tolerated and has a manageable safety profile as a single agent and in combination with atezolizumab. The preliminary safety and clinical activity from dose-escalation warrant further investigation of RG6292. Citation Format: Valentina Gambardella, Michael Ong, Maria Esperanza Rodriguez Ruiz, Jean-Pascal Machiels, Miguel Fernandez de Sanmamed, Josep Maria Tabernero, Anna Spreafico, Daniel J Renouf, Stephen J Luen, Rachel Galot, Bernard Doger de Speville Uribe, Emiliano Calvo Aller, Aung Naing, Samira Curdt, Eva Rossmann, Tamara Tanos, Kevin Smart, Maria Amann, Yuying Xie, Gabriel Schnetzler, Christophe Boetsch, Vaios Karanikas, Theresa Kolben, Linxinyu Xu, Kristoffer S Rohrberg. Safety and anti-tumor activity of a novel Treg depleter RG6292, as a single agent and in combination with atezolizumab in patients with solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT110.