CTIM-25. EO2401 PEPTIDE IMMUNOTHERAPY + NIVOLUMAB +/- BEVACIZUMAB IN FIRST RECURRENT GLIOBLASTOMA: THE PHASE 1/2 EOGBM1-18/ROSALIE STUDY (NCT04116658)

• DOI: 10.1093/neuonc/noad179.0265
• Publication Date: 2023-11-11T23:13:25Z
• Authors: David Reardon; Ahmed Idbaih; Maria Vieito; François Ghiringh...; Agostina Stradella; Ghazaleh Tabatabai; Michael C Burger; Iris Mildenberger; Ulrich Herrlinger; Patrick Wen; Mehdi Touat; Antje Wick; Macarena González; Alice Hervieu; Marta GilMartin; Mirjam Renovanz; Cécile Gouttefangeas; Ana Maia; Christophe Bonny; Jean-Michel Paill...; Laurent Chêne; Jan Fagerberg; Wolfgang Wick
• Keywords: ELISPOT

Abstract EO2401 expands existing memory T cells recognizing protein sequences from gut bacteria, which cross-react with tumor associated antigens (TAAs). contains three CD8 HLA-A2 epitopes mimicry to glioblastoma-TAAs (IL13Rα2, BIRC5, and FOXM1) the CD4 epitope UCP2. Patients received (300μg/peptide, q2weeks x4, then every 4weeks) nivolumab (3mg/kg, q2weeks) in cohorts: C1a (n = 21, Ex2→EN; option for symptom directed low-dose bevacizumab [sLDB; 5mg/kg, q2weeks] as anti-edema treatment); C2a/1 23, EN); C2a/2 15, EN+sLDB); C2b 6, adjuvant C2c 9, neoadjuvant ENx2→surgery→adjuvant C3 26, EN+bevacizumab, q2weeks, 10mg/kg). EO2401/nivolumab+/-bevacizumab safety profile consistent of nivolumab, when applicable bevacizumab, except addition local administration site reactions occurred 39% patients; 96% events Grade 1/2 4% 3. Immune monitoring (peripheral blood, ELISPOT, tetramer assessments) demonstrated expanded mimic specific cross-reactivity against targeted human TAAs. In (83% tested) (81% tested), 89% 95% tested patients showed expansion. Expansions were early (week 2 after starting EO2401), durable (up 23 months), robust (approximately 30% all peripheral 3 clinical responders). C2c, surgery specimens two EO2401/nivolumab doses increased cell infiltration versus pre-treatment 5 6 patients. Addition sLDB prolonged treatment duration vs alone by reducing edema likely worsened study therapy induced immune infiltration. Integration further efficacy C3. C2a/1vsC2a/2vsC3: median 1.4vs3.2vs4.8 months, disease control rate 22%vs40%vs88%, PFS 1.6vs3.6vs5.5 months; survival 9.0vs12.6vstoo (C3 FU 8.3 mo, ongoing up years). Further follow-up will be presented.