EO2401 (E) peptide immunotherapy + nivolumab (N) +/- bevacizumab (B) in recurrent glioblastoma (GB): EOGBM1-18/ROSALIE.

2020 Background: EO2401 was designed to activate/expand existing memory T cells recognizing specific protein sequences from gut bacteria, which cross-react with tumor associated antigens (TAAs). E contains 3 CD8 HLA-A2 epitopes with mimicry to GB-TAAs (IL13Rα2, BIRC5, and FOXM1) and the CD4 epitope UCP2. Methods: Patients (pt) at 1st progression GB received E (300 µg/peptide, q2w x4 then q4w) with N (3 mg/kg q2w) in cohorts: 1a E x2 → EN; 2a/1, 2a/2 and 2b EN from start; 2c EN x2 → surgery → EN; 3/1 and 3/2 EN + B (10mg/kg q2w) (Table). Results: Among 100 treated pt EN+/-B was well tolerated, with E associated events limited to local skin reactions (45% of pt; 96% Grades 1/2, and 4% Grade 3) and N-/B-tox consistent with historical data. EN induced immune response against all 3 mimics in 94% of 35 tested pt (all pt responded against at least 2 mimics), detectable as early as 2 weeks after first EN, and with durations beyond 10 months. Cross-reactivity against human peptides found in 89%. Conclusions: EN +/- B was well tolerated and generated fast and durable immune responses. EN survival like current standards. Delayed N was not advantageous for outcome. sLDB increased trt duration of EN, and improved efficacy. Continuous B plus EN further improved efficacy. Neo-/adjuvant EN was clinically feasible. Updated data, including C3/2 to confirm C3/1, to be presented. Clinical trial information: NCT04116658 . [Table: see text]