Found 1 Presentation For Request "185P"
185P - Interim analysis of the EOGBM1-18 study: Strong immune response to therapeutic vaccination with EO2401 microbiome derived therapeutic vaccine + nivolumab
- Wolfgang Wick (Heidelberg, Germany)
- Wolfgang Wick (Heidelberg, Germany)
- Joao Gamelas Magalhaes (Paris, France)
- Ana Maia Dos Santos Leite (Tuebingen, Germany)
- Ahmed Idbaih (Paris, France)
- Maria Vieito Villar (Barcelona, La, Spain)
- Ghazaleh Tabatabai (Tübingen, Germany)
- Agostina Stradella (Barcelona, Spain)
- Francois Ghiringhelli (Dijon, France)
- Michael Burger (Frankfurt, Germany)
- Iris Mildenberger (Mannheim, Germany)
- Ulrich Herrlinger (Bonn, Germany)
- Mehdi Touat (Paris, France)
- Patrick Wen (Boston, MA, United States of America)
- Antje Wick (Heidelberg, Germany)
- HELENE Toussaint (Paris, France)
- Cécile Gouttefangeas (Tübingen, Germany)
- Christophe Bonny (Paris, France)
- Jean-Michel Paillarse (Paris, France)
- David A. Reardon (Boston, MA, United States of America)
Abstract
Background
EO2401 is a therapeutic vaccine designed to activate memory commensal-specific T cells cross-reacting with tumor-associated antigens (TAAs). EO2401 includes synthetically produced HLA-A2 peptides with molecular mimicry to TAAs (IL13Rα2, BIRC5 and FOXM1) upregulated in glioblastoma, and the CD4 helper peptide UCP2.
Methods
Patients with glioblastoma at first progression after radiotherapy/temozolomide received EO2401 (300μg/peptide, q2w x4 then q4w) with nivolumab (3 mg/kg q2w; EN), or EN with bevacizumab (10 mg/kg q2w; ENB) (NCT04116658). Blood collection was performed at baseline and then every 2-4 weeks. Immune responses were investigated on PBMCs ex vivo or in vitro stimulation (IVS) using tetramer staining, IFN-γ ELISpot and intracellular cytokine staining.
Results
Vaccination with EO2401 induces a strong and durable CD8+ T cell response against bacterial peptides and human TAAs. Immune monitoring using ELISpot demonstrated T cell responses against the 3 microbiome-derived peptides for 97% of patients investigated ex vivo or after IVS. Cross-reactivity against theTAA target peptides was demonstrated in 96% of patients by IFN-γ ELISpot. Frequency of CD8+ T cells against bacterial peptides after IVS is extremely high, with max value above 40% for EO2317 and EO2318. Ex vivo, CD8+ T cell against at least one of the EO2401 peptides or human peptides are detected in almost all evaluable patients with some patients exhibiting up to 5% of circulating specific CD8+ T cells. Polyfunctionality of CD8+ T cell induce upon vaccination was demontrated in most patients (CD107a,IFN-γ and TNF-α production after stimulation). Memory-specific CD8+ T cell response is found as early as 2 weeks after the 1st vaccination and maintenance of a strong immune response could be detected for more than 10 months.
Conclusions
EO2401 vaccine demonstrates ability to generate fast and durable immune responses in patients treated with E02401/nivolumab +/- bevacizumab. Activation of specific T cells cross-reacting with commensal antigens and TAAs is thereby validated as an efficient approach to activate strong immune responses in a difficult to treat tumor. Updated immuno-monitoring data will be presented.
Clinical trial identification
Trial EOGBM1-18 (NCT04116658).
Legal entity responsible for the study
Enterome Sa.
Funding
Enterome Sa.
Disclosure
W. Wick: Financial Interests, Institutional, Funding, Drug/Palbociclib, Torisel for N2M2 trial: Pfizer; Financial Interests, Institutional, Funding, Drug/Asunercept for N2M2: Apogenix; Financial Interests, Institutional, Funding, Drug/Idasanutlin, Atezolizumab, Vismadegib, Alectinib for N2M2: Roche; Financial Interests, Institutional, Invited Speaker: Enterome, Vaximm; Non-Financial Interests, Personal, Leadership Role, Terminated in 2021: NOA; Non-Financial Interests, Personal, Leadership Role: EANO, Deutscher Wissenschaftsrat; Non-Financial Interests, Personal, Leadership Role, terminated in 2021: EORTC; Non-Financial Interests, Personal, Member: Leopoldina/Deutsche Gesellschaft der Wissenschaften. J. Gamelas Magalhaes: Financial Interests, Personal, Stocks/Shares: Enterome. A. IdBaih: Financial Interests, Personal, Advisory Board, Advisory board: Novocure, Leo Pharma, Boehringer Ingelheim, Novartis; Financial Interests, Institutional, Invited Speaker, Clinical research: Enterome, Bristol Myers Squibb, Carthera; Financial Interests, Institutional, Invited Speaker, Basic/Translational research: Carthera; Financial Interests, Institutional, Invited Speaker, Basic and Translational research: Sanofi, Nutrithéragène, Servier, Transgene; Other, Personal, Other, Travel funding: Carthera, Leo Pharma, Novocure, Enterome. All other authors have declared no conflicts of interest.