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

person Wolfgang Wick Universitätsklinikum Heidelberg and German Cancer Research Center, Heidelberg, Germany info_outline Wolfgang Wick, Ahmed Idbaih, Maria Vieito, François Ghiringhelli, Agostina Stradella, Ghazaleh Tabatabai, Michael C. Burger, Iris Mildenberger, Ulrich Herrlinger, Patrick Y. Wen, Mehdi Touat, Antje Wick, Macarena González, Alice Hervieu, Marta Gil-Martin, Mirjam Renovanz, Ana Maia, Christophe Bonny, Jan Fagerberg, David A. Reardon

Authors person Wolfgang Wick Universitätsklinikum Heidelberg and German Cancer Research Center, Heidelberg, Germany info_outline Wolfgang Wick, Ahmed Idbaih, Maria Vieito, François Ghiringhelli, Agostina Stradella, Ghazaleh Tabatabai, Michael C. Burger, Iris Mildenberger, Ulrich Herrlinger, Patrick Y. Wen, Mehdi Touat, Antje Wick, Macarena González, Alice Hervieu, Marta Gil-Martin, Mirjam Renovanz, Ana Maia, Christophe Bonny, Jan Fagerberg, David A. Reardon Organizations Universitätsklinikum Heidelberg and German Cancer Research Center, Heidelberg, Germany, Sorbonne Université, AP-HP, ICM, Hôpital Universitaire La Pitié-Salpêtrière, Paris, France, Hospital Universitari Vall d'Hebron, Barcelona, Spain, Centre Georges-François Leclerc, Dijon, France, Medical Oncology Department-Phase 1 Functional Unit | Catalan Institute of Oncology (ICO), Hospitalet De Llobregat, Barcelona, Spain, Universitätsklinikum, Tübingen, Germany, Universitätsklinikum Frankfurt Goethe-Universität, Frankfurt, Germany, Medizinische Fakultät, Mannheim, Germany, Universitätsklinikum, Bonn, Germany, Dana-Farber Cancer Institute, Boston, MA, Hôpital Universitaire La Pitié-Salpêtrière, Paris, France, Universitätsklinikum, Heidelberg, Germany, Medical Oncology Department-Phase 1 Functional Unit | Catalan Institute of Oncology (ICO), Barcelona, Spain, Department of Immunology, Eberhard-Karls-University, Tübingen, Germany, Enterome, Paris, France Abstract Disclosures Research Funding Other Enterome 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. Cohort 01/16/23 Ongoing treatment (trt) (pt) Trt duration @ Disease Control Rate # Duration of disease control @ Objective response rate PR+CR Progression-free survival @ Survival @ Follow-up survival @ ; pt alive 2a/1 (n=23) EN^ 0% 1.4 (0.03-11.2) 22% 3.6 (1.8-10.2) 9% 1.6 (0.4-11.9) 9.0 (2.8-24.7) 22.1 9% 1a (n=21*) & E => EN^ ₤ 0% ₤ 2.8 (0.03-23.9) 33% 4.1 (2.7-24.0) 5% 1.8 (0.2-24.0) 9.5 (0.4-29.4) 10.0 19% 2a/2 (n=15) & EN^ 20% 3.2 (0.5-11.0) 40% NR (5.2-9.5) 13% 3.6 (0.0-9.5) 12.6 (1.9-14.7) 10.8 47% 2b (n=6) & EN $ 33% 7.9 (2.3-10.9) 83% 9.0 (5.0-9.2) NA $ 7.3 (1.9-9.2) 11.9 (10.1-12.4) 11.5 50% 2c (n=9) & EN^ peri-op 67% NR (0.5-8.5) 88% € NR (0.5-8.0) NA € NR (0.4-8.0) NR (1.1-8.5) 5.6 100% 3/1 (n=11) ENB^ 9% 5.0 (0.5-20.2) 91% 6.0 (3.1-20.2) 55% 6.0 (0.0-20.2) 14.5 (3.0-20.2) 17.2 45% 3/2 (n=15) ENB^ 73% 3.3 (1.4-4.2) 92% ¥ 3.3 (1.7-3.7) 33% ¥ 3.0 (0.0-3.7) NR (1.4-4.4) 3.0 93% NA not applicable; NR not reached. ^Measurable disease; *3 pt in safety lead-in; & Option for symptom driven, time-limited, low-dose B (sLDB; 5 mg/kg q2w), median of 3 doses to 1a=10 pt (56%; NA for 3 pt safety lead-in), 2a/2=5 pt (33%), 2b=1 pt (33%; NA for 3 initial pt), 2c=3 pt (33%); ₤ E mono in 1 pt as individual use after 24 mo study period; $ Non-measurable disease, adjuvant post-surgery in 4 of 6 pt; # Pt with stable disease (SD), partial- or complete response (PR/CR) per iRECIST; @ median (range) in months per Kaplan-Meier; € DCR n=8 (1 pt early), ORR NA, only 2x E admin pre-surgery; ¥ DCR and ORR n=12 (3 pt early), ORR also unconfirmed.

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