Abstract 303P
Background
EO was designed to activate memory T cells cross-reacting with tumor associated antigens. EO includes microbial-derived, synthetically produced HLA-A2 restricted peptides with molecular mimicry to antigens (IL13Rα2, BIRC5 and FOXM1) upregulated in GB, and the CD4 helper peptide UCP2.
Methods
Pts with GB at first progression after radiotherapy/temozolomide received EO (300 μg/peptide, Q2 weeks (w) x 4 then Q4 w), EO with nivolumab (3 mg/kg Q2 w; EN), or EN with bevacizumab (10 mg/kg Q2 w; ENB). Cohort (C) 1 included EO x 2 followed by EN, C2a and C2b evaluated EN without and with surgery, and C3 assessed ENB. 1st endpoint safety; 2nd endpoints immunogenicity and efficacy. NCT04116658.
Results
Part 1 included 40 pts (C1 = 3, C2a = 23, C2b = 3, C3 = 11). Part 2 allowed low-dose bevacizumab (LDB; 5 mg/kg Q2 w up to 6 doses) for symptomatic edema and enrolled 36 additional pts (C1 = 18, C2a = 15, C2b = 3). All evaluable pts demonstrated CD8 T cell ELISPOT responses against the 3 vaccine peptides; including tetramer staining of specific CD8 T cells in 26/27 investigated pts after in vitro stimulation and in 21/22 pts directly ex vivo. Cross-reactivity against targeted TAAs was confirmed in 22/23 pts. EO, EN, and ENB were well tolerated with EO associated tox limited to local administration site reactions (48%; all grade 1-2). The frequency and severity of nivolumab-/bevacizumab-tox was consistent with historical single-agent data. For part 1, median (med) progression-free survival (mPFS), and med survival for EN [C1+C2a+C2b, n=29, med follow-up (mFU) 13.6 months (m)] were 1.8 m and 10.6 m (survival at 12 m 40%). Pts on ENB (C3, n=11, mFU 7.3 m) had mPFS of 5.5 m and 9 pts were alive (7-11 m). Objective Response Rate (ORR)/Disease Control Rate (DCR) (ORR + stable disease) for EN and ENB were 10%/34% and 55%/82%. Med treatment (trt) duration for C2a pts in part 1 was 6.1 w (1/23 on trt; 52% stopped due to neurological symptoms at 1st MRI), while it was 10.0 w (9/15 on trt) for C2a in part 2. Overall, in part 2, 12 pts (33%) received LDB.
Conclusions
EO2401 generated immune responses in all evaluable pts and was well tolerated. Addition of standard bevacizumab to EN improved PFS and ORR/DCR. Symptom driven LDB supported longer trt durations. Outcome of study part 2 will be presented.
Clinical trial identification
NCT04116658.
Editorial acknowledgement
Legal entity responsible for the study
Enterome, 94/96 Avenue Ledru-Rollin, 75011 Paris, France.
Funding
Enterome, 94/96 Avenue Ledru-Rollin, 75011 Paris, France.
Disclosure
D.A. Reardon: Financial Interests, Personal, Advisory Role: Merck, Novocure, regeneron, BMS, Oncorus, Agenus, EMD Serono, Merck KGaA, Taiho Pharmaceuticals, Delmar Pharmaceuticals, Advantagene, Bayer, Imvax, Medicenna, Vivacitas Oncology, Anheart Therapeutics, Ellipses Pharma, Genenta Science, Kintara Therapeutics, Kiyatec, Agios; Financial Interests, Personal, Other, Honoraria: Merck, Novocure, Regeneron, BMS, Oncorus, Agenus, EMD-Serono, Merck KGaA, Taiho Pharmaceutical, Advantagene, Bayer, Delmar Pharamaceuticals, Imvax, Medicenna, Sumitomo Dainippon Pharma, Vivacitas Oncology, Anheart Oncology, Deciphera, Ellipses Pharma, Genenta Science, Inovio Pharmaceuticals, Kintara Therapeutics, Kiyatec, Neuvogen, Taiho Pharmaceutical, Y-mAbs Therapeutics; Financial Interests, Personal, Research Grant, Honoraria: Omniox; Financial Interests, Institutional, Research Grant: Celldex, Incyte , Agenus, Serono, Acerta Pharma, Enterome. A. Idbaih: Financial Interests, Personal, Invited Speaker, Honoraria: Novocure, Leo Pharma; Financial Interests, Personal, Advisory Role: Health Advances; Financial Interests, Institutional, Research Grant: CarThera, Transgene, Sanofi, Ail Liquide, Nutritheragene, Servier; Financial Interests, Personal, Other, Travel, Accomodation, expenses: CarThera, Leo Pharma, Novocure. M. Vieito Villar: Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Other, Travl, accomodation, expenses: Roche. G. Tabatabai: Financial Interests, Personal, Other, Honoraria: AbbVie, Bayer; Financial Interests, Personal, Advisory Role: AbbVie, Bayer, Boehringer Ingelheim. F. Ghiringhelli: Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Institutional, Research Grant: AstraZeneca/Medimmmune; Financial Interests, Personal, Other, Travel, accomodation, expenses: Roche/Genentech, Amgen. M. Renovanz: Financial Interests, Personal, Research Grant: German Innovation Fund. M. Touat: Financial Interests, Personal, Advisory Role: Agios, Integragen, Taiho Pharmaceuticals, Servier; Financial Interests, Personal, Research Grant: Sanofi; Financial Interests, Personal, Other, Travel, accomodation, expenses: Servier, MSD. P. Wen: Financial Interests, Personal, Advisory Role: Agios, AstraZeneca, VascularBiogenics, VBI Vaccines, Tocagen, Bayer, Blue Earth Giagnostics, Karyopharm Therapeutics, Voager Therapeutics, QED Therapeutics, Imvax, ElevateBio, Integral Health, Prelude Therapeutics, Novocure, Mundipharma, Black Diamond therapeutics, Day One Biopharmaceuticals, Sapience Therapeutics, Nuvation Bio, Celularity, Novartis, Merck, Boston Pharmaceuticals, Chimerix; Financial Interests, Institutional, Research Grant: Agios, AstraZeneca, Merck, Novartis, Oncoceutics, Lilly, Beigene, Kazia Therapeutics, MediciNova, Vascular Biogenics, VBI Vaccines, Puma Biotechnology, Celgene, Bayer, Nuvation Bio, Chimerix, Karyopharm Therapeutics. C. Gouttefangeas: Financial Interests, Personal, Research Grant: Enterome, Rhovac; Financial Interests, Personal, Royalties: Rhovac, Immunology Dpepartment Tübingen. A. Maia: Financial Interests, Personal, Research Grant: Enterome. C. Bonny: Financial Interests, Personal, Leadership Role: Enterome. J. Fagerberg: Financial Interests, Personal, Leadership Role: Enterome; Financial Interests, Personal, Stocks/Shares: Enterome. W. Wick: Financial Interests, Institutional, Advisory Role: MSD Oncology, Roche/ Genentech; Financial Interests, Institutional, Research Grant: Roche, Apogenix, Pfizer. All other authors have declared no conflicts of interest.