162P - EO4010 (EO) + nivolumab (N) ± bevacizumab (B) in patients (pts) with microsatellite stable (MSS) metastatic colorectal carcinoma (mCRC)

Background

EO is designed to expand pre-existing memory CD8 T cells cross-reacting with tumor associated antigens (TAAs). EO is composed of microbial-derived sequences mimicking HLA-A2 epitopes on 5 TAAs, BIRC5, FOXM1, UBE2C, CDC20 and KIF2C and a CD4 peptide. This phase 1/2 trial, EOCRC2-22, assesses safety and efficacy of EO + N ± B in MSS mCRC based on clinical effects in other MSS tumors by EO2401, a similar compound to EO.

Methods

Pts were HLA-A2 and had MSS mCRC, previously treated with FU, oxaliplatin, irinotecan and anti-VEGF/EGFR. In Cohort (C)1 safety lead-in followed by expansion C2, pts received EO (300 μg/peptide in Montanide q2 weeks (w) x4 then q4w) + N (240 mg q2w x3 then 480 mg q4w; in C1 first 2 doses of N omitted). In C3 B 5mg/kg q2w was added to EO + N.

Results

25 pts (C1=3, C2=17, C3=5) started EO. No safety concerns in C1. Most common any grade (G; n=25) treatment related adverse events (AE): injection site reaction (ISR) (80%), asthenia (20%) and fatigue (12%). G 3 related ISR in 2 pts; no other related AE ≥ G 3. EO + N discontinued (D) due to non-related myocardial infarction death in 1 pt; other D due to progressive disease (PD; 20 pts) and 1 pt wish. Median (m) treatment duration 8 w (range 4-28 w; n=25); m follow-up 28 w (range 10-53 w). CD8 T cells against EO (tetramers staining of PBMC ex vivo) found in 12/13 tested patients, with cross-reactivity against TAAs in the 12 positive pts. Response durability currently until w25; pt with 23% EO/8% TAA specific CD8 T cells. After w5 >80% of specific T cells were effector memory cells. In C2 kinetics of EO T cell detection in periphery different in pts with partial response (PR)/stable disease (SD) vs PD; 3 pts with PR/SD longer time to detection (m w9) vs 6 pts with PD (m w3); p=0.018. C2 efficacy: 1 PR (treatment >w28; mets liver -35%, lung -40%; CEA normalized), 1 SD (mets lung -7%; CEA -68%, CA19-9 -36%), 1 SD >w17; 14 pts had PD, including 6 pts with SD in target lesions (TL) but unequivocal progression in non-TL (2/6 decreased CEA; -16%, -19%). In C3, 3 SD (2 ongoing w13/w16; 1 normalized CEA) and 2 PD in TLs.

Conclusions

EO4010 + N promotes expansion of TAA specific CD8 T cells and shows good safety and interesting preliminary efficacy in previously treated MSS mCRC. B can be safely added and might improve efficacy.

Clinical trial identification

Company protocol number and name: EOCRC2-22 / AUDREY NCT05589597 EudraCT: 2022-002805-90 EUCT number: 2023-509509-62-00 US IND: 28,848.

Legal entity responsible for the study

Enterome.

Funding

Enterome.

Disclosure

R. Cohen: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Exeliom Biosciences, Enterome Biosciences; Financial Interests, Personal, Invited Speaker: Pierre Fabre, MSD Oncology, Servier, AstraZeneca; Financial Interests, Personal, Research Grant: Servier Institute. M.E. Elez Fernandez: Financial Interests, Personal, Advisory Board: Agenus Inc., Amgen, Bayer, Boehringer Ingelheim, Cure Teq AG, Hoffman La - Roche, Janssen, MSD, Merck Serono, Pierre Fabre, RIN Institute Inc., Repare Therapeutics Inc., Sanofi, Servier, Takeda; Financial Interests, Personal, Invited Speaker: BMS, Lilly, Medscape, Novartis, Organon, Pfizer; Financial Interests, Personal, Other, Steering Committee: GSK; Financial Interests, Personal, Other, Educational training: Seagen International GmbH; Financial Interests, Institutional, Funding: AbbVie Deutschland GmbH & Co KG, Amgen Inc., Array Biopharma Inc., AstraZeneca Pharmaceuticals LP, Bayer Pharma AG, BeiGene, Bioncotech Therapeutics, S.L., BioNTech Rna Pharmaceuticals GMBH, BioNTech Small Molecules GMBH, Boehringer Ingelheim, Boehringer Ingelheim de España S.A., Bristol Myers Squibb International Corporation, Celgene International SARL, Daiichi Sankyo, Inc., Debiopharm International SA, Genentech Inc., Gercor, HalioDX SAS, Hoffmann-La Roche Ltd, Hutchinson Medipharma Limited, Hutchison MediPharma International, Iovance Biotherapeutics, Inc., Janssen Research & Development, Janssen-Cilag SA, MedImmune, Menarini, Menarini Ricerche SPA, Merck Health KGAA, Merck Sharp & Dohme de España SA, Merus NV, Mirati, Nouscom SRL., Novartis Farmacéutica SA, Pfizer, PharmaMar SA, Pledpharma AB, Redx Pharma PLC, Sanofi Aventis Recherche & Développement, Scandion Oncology, Seattle Genetics Inc., Servier, Sotio A.S., Taiho Pharma USA Inc., Wntresearch AB; Non-Financial Interests, Personal, 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, Personal, Other, Speaker of the ESMO Academy: European Society for Medical Oncology (ESMO); Non-Financial Interests, Personal, Other, Member of the Scientific Committee 2024: European Society for Medical Oncology (ESMO); Non-Financial Interests, Personal, Other, Coordinator of the SEOM +MIR Section of Residents and Young Assistants: Sociedad Española de Oncología Médica (SEOM); Non-Financial Interests, Personal, Other, Member of the Scientific Committee SEOM Annual Meeting, 2024-2025 term: Sociedad Española de Oncología Médica (SEOM); Other, Personal, Other, Travel, accommodations, expenses; Agenus Inc., Amgen, BMS, Bayer, Boehringer Ingelheim, Cure Teq AG, GSK, Hoffman La-Roche, Janssen, Lilly, MSD, Medscape, Merck Serono, Novartis, Organon, Pfizer, Pierre Fabre, RIN Institute Inc., Repare Therapeutics Inc., Sanofi, Seagen, Servier, Takeda. N. Tarazona Llavero: Financial Interests, Personal, Advisory Board: Merck, Guardant Health, Grifols; Financial Interests, Personal, Invited Speaker: Merck, Pfizer, Servier, Amgen; Financial Interests, Institutional, Funding: Natera Inc., Guardant Health; Non-Financial Interests, Personal, Member: SEOM Committee. N.A. Dasari: Financial Interests, Personal, Advisory Board: HutchMed, Exelixis, Personalis, Illumina, Takeda; Financial Interests, Institutional, Trial Chair: HutchMed, Eisai, Guardant Health, Natera, Xencor, Taiho; Financial Interests, Institutional, Coordinating PI: Enterome. T. Mazard: Financial Interests, Personal, Advisory Board: Pierre Fabre, Pierre Fabre, Servier; Financial Interests, Personal, Invited Speaker: Servier, Sanofi, Pierre Fabre; Financial Interests, Personal, Other, Development of clinical cases for regional meetings: Merck Serono; Financial Interests, Personal, Writing Engagement: Galapagos; Financial Interests, Institutional, Coordinating PI: Amgen; Non-Financial Interests, Personal, Advisory Role, development of guidelines about molecular testing in colorectal cancers: INCA; Other, Personal, Other, travel grant: Pierre Fabre, Merck Serono, Sanofi, MSD. H. Toussaint, L. Aubergeon, L. Chêne, S. Balandraud: Financial Interests, Personal, Full or part-time Employment: Enterome. J. Fagerberg: Financial Interests, Personal, Full or part-time Employment: Enterome; Financial Interests, Personal, Ownership Interest: Enterome. H.J.E. Schmoll: Financial Interests, Personal, Advisory Board, Chair, IDMC for all ongoing trials: Enterome; Financial Interests, Personal, Other, Member, Advisory board: TREOS; Financial Interests, Personal, Other, Adboard: DoMore DX; Financial Interests, Institutional, Coordinating PI: Roche; Non-Financial Interests, Personal, Principal Investigator, CHARTA Trial in advanced CRCModul trial: Roche; Non-Financial Interests, Personal, Member, Speaker, Chair, program committee member in the past: ASCO. A. Cervantes: Financial Interests, Institutional, Advisory Board: Merck Serono, Amgen, Roche, Transgene, AnHeart Therapeutics, AbbVie, GSK; Financial Interests, Institutional, Invited Speaker: Amgen, Roche, Merck Serono, Foundation Medicine; Financial Interests, Personal, Other, Associate Editor: Annals of Oncology, ESMO Open; Financial Interests, Personal, Other, Editor in Chief: Cancer Treatment Reviews; Financial Interests, Institutional, Research Grant, Principal Investigator: Actuate Therapeutic, Amgen, Astellas Pharma, Beigene, Bayer, AstraZeneca, BMS, Amcure, FibroGen, Lilly, Genentech, MedImmune, Merck Serono, Novartis, Natera, MSD, Servier, Sierra Oncology, Adaptimmune, Takeda, Affimed, Roche, Seamless, Gilead, Janssen, F. STAR Therapeutics, Ribon Therapeutics; Non-Financial Interests, Personal, Other, Scientific Director: INCLIVA Biomedical Research Institute. S. Kopetz: Financial Interests, Personal, Advisory Board, Consultant: Roche, Merck, Bayer, Pfizer, Genentech, Lutris, Aveo, Tachyon Therapeutics, Agenus, Revolution Medicines, Kestrel Therapeutics, Regeneron; Financial Interests, Personal, Advisory Board: Mirati, Flame, Carina; Financial Interests, Personal, Other, Consultant: Frontier Medicines, Replimune, Bristol Myers Squibb-Medarex, Amgen, Tempus, Harbinger Oncology, Zentalis; Financial Interests, Personal, Other, Research: Sanofi, Guardant Health, Genentech/Roche, EMD Serono, MedImmune, Novartis; Financial Interests, Personal, Advisory Board, Research: Amgen, Lilly, Daiichi Sankyo, Pfizer, Boehringer Ingelheim, BridgeBio, Cardiff, Jazz, Zentalis, Mirati; Financial Interests, Personal, Stocks/Shares: Lutris, Navire; Financial Interests, Personal, Ownership Interest: Frontier Medicines. J. Tabernero: Financial Interests, Personal, Advisory Board, scientific consultancy role: Orion Biotechnology, AstraZeneca, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc., Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Scandion Oncology, Ona Therapeutics, Sotio Biotech, Inspirna Inc., Scorpion Therapeutics, Tolremo Therapeutics, CARsgen Therapeutics, hC Bioscience Inc., Takeda Pharmaceuticals International AG, Alentis Therapeutics, Immodulon Therapeutics; Financial Interests, Personal, Invited Speaker, educational collaboration: Medscape Education, Physicians Education Resource (PER), PeerView Institute for Medical Education, Imedex / HMP; Financial Interests, Personal, Advisory Board: Cardiff Oncology, Aveo Oncology; Financial Interests, Personal, Other, scientific consultancy: Ono Pharma USA Inc; Financial Interests, Personal, Stocks/Shares: Oniria Therapeutics, 1TRIALSP, Alentis Therapeutics, Pangaea Oncology; Financial Interests, Institutional, Research Grant, ACRCelerate: Colorectal Cancer Stratified: Fundación Científica de la Asociación Española Contra el Cáncer; Financial Interests, Institutional, Research Grant, OPTIMISTICC: Opportunity to Investigate the Microbiome’s Impact on Science and Treatment In Colorectal Cancer: Cancer Research UK; Financial Interests, Institutional, Funding, Clinical Trials & Research: Amgen Inc., AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb International Corporation, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc., Janssen-Cilag International NV, Merck Health KGAA, Merck, Sharp & Dohme de España, SA, Novartis Farmacéutica SA, PharmaMar SA, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA, Inc., BeiGene, Boehringer Ingelheim, Menarini, Merus N V, Pfizer, Mirati; Non-Financial Interests, Personal, Member of Board of Directors, Board of Directors: Cancer Core Europe, Spanish Association Against Cancer -AECC; Non-Financial Interests, Personal, Member of Board of Directors, General Assembly: Horizon Europe Cancer Mission; Non-Financial Interests, Personal, Leadership Role, External Scientific Committee: Institute for Health Research INCLIVA – Clinical Hospital of Valencia, IdiSNA –Universidad de Navarra; Non-Financial Interests, Personal, Leadership Role, Scientific Advisory Board: Spanish National Cancer Research Centre (CNIO); Non-Financial Interests, Personal, Advisory Role, International Scientific Evaluation Committee: Bosch Health Campus (BHC); Non-Financial Interests, Personal, Advisory Role, Review Board: National Decade Against Cancer (NCT) - German Consortium for Translational Cancer Research (DKTK); Non-Financial Interests, Personal, Advisory Role, Scientific Advisory Board: Karolinska Comprehensive Cancer Centre; Non-Financial Interests, Personal, Advisory Role, International Review Committee (IRC): Oncode Institute; Non-Financial Interests, Personal, Advisory Role, Scientific Advisory Board (SAB): Oslo University Hospital Comprehensive Cancer Centre (OUH CCC); Non-Financial Interests, Personal, Leadership Role, Governance Advisory Committee: European Organization for Research and Treatment of Cancer -EORTC; Non-Financial Interests, Personal, Leadership Role, Vice Chairman: World Innovative Networking (WIN) Consortium in Personalized Cancer Medicine; Non-Financial Interests, Personal, Other, Coordinating PI & Steering Committee Member. Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutical LP, Boehringer Ingelheim, MedImmune, Menarini, Merck Healthcare KGAA, Merck, Sharp & Dohme de España SA, Pfizer, Servier; Non-Financial Interests, Personal, Principal Investigator, Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutics LP, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb International Corporation, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc., HalioDX SAS, Hutchinson Medipharma, Janssen-Cilag International NV, MedImmune, Menarini, Merck Healthcare KGAA, Merck, Sharp & Dohme de España SA, Merus NV, Mirati, Novartis Farmacéutica SA, Pfizer, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA Inc; Non-Financial Interests, Personal, Other, Steering Committee Member. Clinical Trials & Research: Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc., HalioDX SAS, Hutchinson Medipharma, Janssen-Cilag International NV, Merus NV, Taiho Pharma USA Inc; Non-Financial Interests, Personal, Other, Coordinating PI. Clinical Trials & Research: Mirati; Non-Financial Interests, Personal, Member: AACR, ASCO, EACR, EORTC, SEOM; Other, Personal, Other, President: Oncology Master Plan – Catalonia Department of Health; Other, Personal, Other, Advisory Committee: Advisory Committee on Pharmaceutical Provision Financing under the Spanish National Health System. All other authors have declared no conflicts of interest.