Abstract 170P
Background
EO2401 was designed to activate memory T cells cross-reacting with tumor associated antigens and includes synthetically produced HLA-A2 peptides with molecular mimicry to antigens (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 (300 μg/peptide, q2w x4 then q4w) with nivolumab (3 mg/kg q2w; EN), or EN with bevacizumab (10 mg/kg q2w; ENB). In study part 2, low-dose bevacizumab (5 mg/kg q2w) could be used as symptom directed time-limited treatment of edema. In study part 3, 6 evaluable patients are to be treated with neoadjuvant EN, and 15 further patients with ENB (enrollment ongoing).
Results
Part 1 included 40 patients (EN = 29, ENB = 11). Part 2 enrolled 36 patients treated with EN. EN and ENB (n=76) were well tolerated with EO2401 associated tox limited to local administration site reactions (45% of patients; events 70% Grade 1, 26% Grade 2, and 4% Grade 3). The frequency and severity of nivolumab-/bevacizumab-tox was consistent with historical single-agent data. Immune monitoring demonstrated T cell responses against the 3 microbiome-derived peptides for 97% of patients investigated ex vivo or after in vitro stimulation (IVS). Cross-reactivity against the pool of 3 human target peptides was demonstrated in 96% of patients by IFN-γ ELISpot. The strength of the immune response correlated with clinical outcome (progression-free survival [PFS] and objective responses [OR]). For part 1, median PFS, and median survival for EN (n=29, median follow-up 20.1 months) were 1.8 and 10.6 months. Patients on ENB (n=11, median follow-up 13.1 months) had median PFS of 5.5 months and 55% of patients were alive beyond 12 months. OR rate / Disease Control Rate (DCR) (OR rate + stable disease) for EN and ENB were 14%/34% and 55%/82%.
Conclusions
EO2401 was well tolerated and generated rapid and durable immune responses correlating with clinical outcome. Addition of standard bevacizumab to EN improved efficacy. Updated data from all parts of the trial will be presented. NCT04116658.
Clinical trial identification
NCT04116658.
Legal entity responsible for the study
Enterome.
Funding
Enterome.
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. 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. M. Vieito Villar: Financial Interests, Personal, Advisory Role: Roche. G. Tabatabai: Financial Interests, Personal, Advisory Role: AbbVie, Bayer, Boehringer Ingelheim; Financial Interests, Personal, Other, Honoraria: AbbVie, Bayer. A. Stradella: Financial Interests, Personal, Advisory Role: Novartis, Seagen; Financial Interests, Personal, Speaker’s Bureau: Novartis, Pierre Fabre. F. Ghiringhelli: Financial Interests, Personal, Other, Honoraria: Roche, Amgen, Astra-Zeneca; Financial Interests, Personal, Advisory Role: Enterome; Financial Interests, Personal, Other, Research Funding: Astra-Zeneca, Roche; Financial Interests, Personal, Other, Travel, accomodation, expenses: Roche; Financial Interests, Personal, Other, Travel, Accomodation expenses: Amgen, Servier. M. Burger: Financial Interests, Personal, Speaker’s Bureau: Bristol-Myers, Gilead. U. Herrlinger: Financial Interests, Personal, Advisory Role: Bayer Pharma; Financial Interests, Personal, Invited Speaker: Medac. M. Touat: Financial Interests, Personal, Advisory Role: Agios, Servier, Integragen, Taiho Pharmaceuticals; Financial Interests, Institutional, Other, Research Funding: Sanofi. P. Wen: Financial Interests, Personal, Research Grant: AstraZeneca/ MedImmune, Beigene, Celgene, Chimerix, Genentech/Rochee, Kazia, MediciNova, Merck, Novartis, Nuvation Bio, Puma, Servier, Vascular Biogenics, VBI Vaccines, Eli Lilly; Financial Interests, Personal, Advisory Board: Astra-Zeneca, Bayer, Black Diamond, Boston Pharmaceuticals, Boehringer Ingelheim, Celularity, Chimerix, Day One Bio, Genenta, GSK, Karyopharm, Merck, Mundipharma, Novartis, Novocure, Nuvation Bio, Prelude Therapeutics, Sapience, Servier, Sagimet, Vascular Biogenics, VBI Vaccines. C. Gouttefangeas: Financial Interests, Personal, Other, Research funding: Enterome; Financial Interests, Personal, Royalties, Patent and Intellectual property: Tübinge University. A. Maia: Financial Interests, Personal, Other, Research Funding: Enterome. C. Bonny: Financial Interests, Personal, Full or part-time Employment: Enterome; Financial Interests, Personal, Stocks/Shares: Enterome. J. Paillarse: Financial Interests, Personal, Full or part-time Employment: Enterome; Financial Interests, Personal, Stocks/Shares: Enterome. J. Fagerberg: Financial Interests, Personal, Full or part-time Employment: Enterome; Financial Interests, Personal, Stocks/Shares: Enterome. D.A. Reardon: Financial Interests, Personal, Research Grant: Celldex, Incyte, Agenus, EMD Serono, Acerta Pharma, Omniox, Enterome; Financial Interests, Personal, Speaker’s Bureau: Merck, Novocure, Regeneron, BMS, Oncorus, Agenus, EMD Serono, Merck KGaA, Taiho Pharmaceuticals, Advantagene, Bayer, Imvax, Medicennnac, Sumitom Dainippon Pharma, Vivacitas Oncology, Anheart Therapeutics, Deciphera, Ellipses Pharma, Genenta Science, Inir Pharma, Kintara Therapeutics, Kyatec, Neuvogen, Y-mAbs; Financial Interests, Personal, Advisory Board: Merck, Novocure, Regeneron, BMS, Oncorus, Agenus, EMD Serono, Merck KGaA, Taiho Pharmaceuticals, Advantagene, Bayer , Imvax, Medicenna, Vivacitas Oncology, Anheart Therapeutics, Ellipses Pharma, Genenta Science, Kintara Therapeutics; Financial Interests, Personal, Invited Speaker: Kiyatec, Agios. All other authors have declared no conflicts of interest.