Abstract 29P
Background
Autogene cevumeran is an intravenously administered uridine mRNA based, lipoplex-formulated Individualized NeoAntigen Specific Immunotherapy (iNeST) designed to stimulate an immune response against up to 20 patient-specific tumor neoantigens. In the ongoing phase 2 clinical trial BNT122-01 (NCT04486378), pts with Stage II (high risk)/Stage III CRC who are circulating tumor DNA (ctDNA) positive following tumor resection and are subsequently treated with a standard of care (SOC) adjuvant chemotherapy (ACT), receive autogene cevumeran as adjuvant vaccine versus watchful waiting. Here, we report the immunogenicity results of the biomarker cohort of BNT122-01 that enrolled pts irrespective of post-surgical ctDNA status.
Methods
Pts must have completed surgical resection and SOC ACT with no evidence of disease at enrollment and receive up to 15 doses of autogene cevumeran. Blood samples are collected for immune monitoring at baseline, after 8 doses (71 days), 15 doses (359 days) and 1 year post last dose of autogene cevumeran. T cell immune responses to vaccine-encoded neoantigens are characterized by ex vivo IFNγ ELISpot, multimer staining, neoantigen-specific TCR discovery and intracellular cytokine staining. The biomarker cohort is not subject to primary endpoint analysis.
Results
Autogene cevumeran induced de novo T-cell response against >1 (median=3, range 1–10) vaccine-encoded antigen in 11/11 assessed pts as shown by ex vivo ELISpot. After 8 doses, up to 42% of total circulating CD8+ TCRs were vaccine antigen specific, with a median 9% (range: 3–42%) detected in 8 pts by TCR sequencing. Neoantigen-specific T cells had predominantly effector memory phenotype (CD45RA-CCR7-) and expressed PD-1. All 11 pts were disease-free at median follow-up of 640 days (range 602–779 days).
Conclusions
In adjuvant CRC pts, autogene cevumeran induces poly-epitopic neoantigen-specific T-cell responses of high magnitude in all pts treated. Long-term immune response data will be presented. Autogene cevumeran is being jointly developed by BioNTech and Genentech, member of Roche Group.
Clinical trial identification
NCT04486378.
Editorial acknowledgement
Medical writing support was provided by Andrew Finlayson and Olga Ucar of BioNTech.
Legal entity responsible for the study
BioNTech SE.
Funding
BioNTech SE.
Disclosure
M.E. Elez Fernandez: Financial Interests, Personal, Advisory Board: Hoffmann-La Roche, Servier, Amgen, Merck Serono, Sanofi, Bayer, Pierre Fabre, MSD, Takeda, Boehringer Ingelheim, Cure Teq AG, Repare Therapeutics Inc., RIN Institute Inc., Janssen; Financial Interests, Personal, Invited Speaker: Organon, Novartis, Pfizer, BMS, Lilly, Medscape; Financial Interests, Personal, Other, Educational training: Seagen International GmbH; Financial Interests, Institutional, Funding: Hoffmann-La Roche Ltd., Sanofi Aventis Recherche & Dévelopement, Amgen Inc., Boehringer Ingelheim, Novartis Farmacéutica SA, Bristol Myers Squibb International Corporation, BeiGene, HalioDX SAS, Janssen-Cilag SA, Merck Health KGaA, Merck Sharp & Dohme de España SA, PharmaMar SA, Servier, Taiho Pharma USA Inc, Hutchison MediPharma International, Menarini, Merus NV, Pfizer, Mirati, Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, Celgene International SARL, Debiopharm International SA, Genentech Inc, MedImmune, AbbVie Deutschland GmbH & Co KG, Bayer Pharma AG, Bioncotech Therapeutics, S.L., BioNTech RNA Pharmaceuticals GmbH, BioNTech Small Molecules GmbH, Boehringer Ingelheim de España S.A., Daiichi Sankyo, Inc, Gercor, Hutchinson Medipharma Limited, Iovance Biotherapeutics, Inc., Janssen Research & Development, Menarini Ricerche SPA, Merck, Sharp & Dohme De España S.A., Nouscom SRL., Pledpharma AB, Redx Pharma PLC, Scandion Oncology, Seattle Genetics Inc., Sotio A.S., Wntresearch AB; Non-Financial Interests, Other, Coordinator of the SEOM +MIR Section of Residents and Young Assistants: Sociedad Española de Oncología Médica (SEOM); Non-Financial Interests, Other, Speaker of the ESMO Academy: European Society for Medical Oncology (ESMO); Non-Financial Interests, Other, Volunteer member of the ASCO Annual Meeting Scientific Program Committee: Developmental Therapeutics – Immunotherapy: American Society of Clinical Oncology (ASCO); Non-Financial Interests, Leadership Role, Member of the Scientific Program Committee and Developmental Therapeutics-Immunotherapy Track Leader, 2023-2024 term: American Society for Clinical Oncology (ASCO); Non-Financial Interests, Other, Member of the Scientific Committee 2024: European Society for Medical Oncology (ESMO); Other, Travel, accommodation, expenses: Roche, Merck Serono, Sanofi, Amgen, Array BioPharma, Servier, Bristol Myers Squibb. J. Maurel: Financial Interests, Personal, Advisory Board: Advance Medical, Cancer Expert Now, MSD; Financial Interests, Personal, Other, Financial travel and congress: Amgen; Financial Interests, Institutional, Invited Speaker: Amgen, Merck, Guardant, Terumo; Financial Interests, Institutional, Funding: Incyte; Non-Financial Interests, Leadership Role: GEMCAD (Grupo Español Multidisciplinar en Cancer Digestivo). V. Morris: Financial Interests, Personal, Advisory Role: Incyte, Regeneron, Novartis; Financial Interests, Institutional, Funding: Bristol Myers Squibb, EMD Serono, Pfizer, BioNTech, Bicara Therapeutics, Sumitomo Pharma Oncology, Redx Pharma. S. Kopetz: Financial Interests, Personal, Advisory Board: Roche, EMD Serono, Merck, Novartis, Lilly, Boehringer Ingelheim, Boston Biomedical, AstraZeneca, Bayer, Pierre Fabre, Redx Pharma, Ipsen, Daiichi Sankyo, Natera, HalioDx, Jacobio, Pfizer, Repare Therapeutics, GSK, Jazz, Xilis, AbbVie, Gilead, Mirati, Flame, Servier, Carina, Bicara, Endeavor BioMedicines, Numab Pharma, Janssen; Financial Interests, Personal, Other, Research: Inivata, Sanofi, Biocartis, Guardant Health, Array BioPharma, Genentech/Roche, EMD Serono, MedImmune, Novartis; Financial Interests, Personal, Other, Consultant: Genomic Health, Frontier Medicines, Replimune, Taiho Pharmaceutical, Cardiff Oncology, Ono Pharmaceutical, Bristol Myers Squibb-Medarex, Amgen, Tempus, Foundation Medicine, Harbinger Oncology, Takeda, CureTeq, Zentalis, Black Stone Therapeutics, NeoGenomics Laboratories, Accademia Nazionale di Medicina; Financial Interests, Personal, Stocks/Shares: Lutris, Iylon, Navire, Xilis; Financial Interests, Personal, Ownership Interest: Frontier Medicines. E. Derhovanessian, K. Unsal-Kacmaz, L. Manning, H. Henn, T. Weisenburger, M. Tonigold, P. Zurek, M. Fierek-Ulbig, A. Cortini, M. Pino Claveria, L. Preussner, F. Mueller: Financial Interests, Personal, Full or part-time Employment: BioNTech; Financial Interests, Personal, Stocks/Shares: BioNTech. î Türeci: Financial Interests, Personal, Full or part-time Employment: BioNTech; Financial Interests, Personal, Leadership Role: BioNTech; Financial Interests, Personal, Stocks/Shares: BioNTech; Financial Interests, Personal and Institutional, Funding, Research funding: BioNTech, HI-TRON Mainz; Financial Interests, Personal, Royalties: BioNTech, HI-TRON Mainz; Financial Interests, Personal, Other, Travel, accommodation, expenses: BioNTech; Non-Financial Interests, Personal, Advisory Role, Scientific management board: HI-TRON Mainz; Non-Financial Interests, Personal, Leadership Role, President of the Association for Cancer Immunotherapy: CIMT. U. Sahin: Financial Interests, Personal, Full or part-time Employment: BioNTech; Financial Interests, Personal, Stocks/Shares: BioNTech; Financial Interests, Personal, Leadership Role: BioNTech; Financial Interests, Personal and Institutional, Funding, Research funding: BioNTech; Financial Interests, Personal, Royalties: BioNTech, TROn; Financial Interests, Personal, Other, Travel, accommodation, expenses: BioNTech; Non-Financial Interests, Personal, Leadership Role, Co-founder, scientific advisor at TRON; member of the Scientific management board of HI-TRON: TRON. All other authors have declared no conflicts of interest.