Abstract 357P
Background
Although the clinical development of Io has ushered in a new era of anti-tumor therapy, mCRC is considered to be an immune-excluded tumor, being one of the tumor types in which Io has proven to be less effective. Microsatellite instability (MSI) status is currently the only biomarker for Io response in mCRC, being present in only 5% of mCRC pts. Most pts with microsatellite stability (MSS) mCRC do not respond to Io or do not have durable clinical responses, therefore it is necessary to obtain reliable predictors of response to Io. Here we report a novel potential biomarker based on RNA expression data.
Methods
The VIGex test is a gene expression panel using RNA data, developed from a set of 12 immune-related genes (interferon-γ signaling, T-cell exhaustion, Tregs, tumor-associated macrophages, and anti-inflammatory cytokines). Gene expression analysis was performed using Nanostring nCounter and analyzed with nSolver software and R in-house scripts. After intra- and inter-run normalization, an unsupervised hierarchical clustering with Ward’s minimum variance method and correlation-based distance was performed. 3 clusters (hot, intermediate (iCold), and cold) were defined by an unsupervised hierarchical clustering of the VIGex results.
Results
Overall, 383 pts with VIGex test and mCRC were detected. 254 (66%) tissue samples were obtained from the metastatic site and 129 (34%) from the primary site. 105 pts were classified as hot (28%), 223 as iCold (58%), and 55 as Cold (14%). A correlation between immune-related gene expression and cluster score VIGex classification was seen, as the cluster of cold VIGex tumors showed low expression of immune-related genes, and the Hot VIGex tumor cluster was associated with high expression of immune-related genes.
Conclusions
Our results shows that the VIGex score reflects the immune microenvironment status of mCRC, being a potential predictive biomarker to Io to explore in this subset of pts. This feasible test could be an enrichment strategy to improve selection of MSS mCRC pts exploring the use of Io in clinical trials.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
F.J. Ros Montana: Financial Interests, Institutional, Invited Speaker: Sanofi; Other, Other, Travel and accommodation expenses: Amgen, Pierre-Fabre, Merck, Sanofi. I. Baraibar Argota: Financial Interests, Personal, Invited Speaker: Sanofi. F. Salvà Ballabrera: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Invited Speaker: Sanofi, Merck, Servier, Roche. J. Tabernero: Financial Interests, Personal, Advisory Board, scientific consultancy role: Orion Biotechnology, Array Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Daichii Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc., HalioDX SAS, Ikena Oncology, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Tessa Therapeutics, TheraMyc, Hutchinson MediPharma International, Avvinity, Scandion Oncology, Ona Therapeutics, Sotio Biotech, Inspirna Inc; Financial Interests, Personal, Invited Speaker, educational collaboration: Medscape Education, Physicians Education Resource (PER), PeerView Institute for Medical Education, Imedex; Financial Interests, Personal, Invited Speaker, educacional collaboration: MJH Life Sciences; 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, Array Biopharma 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, HalioDX SAS, Hutchinson Medipharma, MedImmune, Menarini, Merus N V, Pfizer, Mirati; Non-Financial Interests, Invited Speaker, Board of Directors: Cancer Core Europe, Spanish Association Against Cancer -AECC; Non-Financial Interests, Invited Speaker, General Assembly: Horizon Europe Cancer Mission; Non-Financial Interests, Leadership Role, External Scientific Committee: Institute for Health Research INCLIVA – Clinical Hospital of Valencia, IdiSNA –Universidad de Navarra; Non-Financial Interests, Leadership Role, Scientific Advisory Board: Spanish National Cancer Research Centre (CNIO); Non-Financial Interests, Advisory Role, International Scientific Evaluation Committee: Bosch Health Campus (BHC); Non-Financial Interests, Advisory Role, Review Board: National Decade Against Cancer (NCT) - German Consortium for Translational Cancer Research (DKTK); Non-Financial Interests, Advisory Role, Scientific Advisory Board: Karolinska Comprehensive Cancer Centre; Non-Financial Interests, Advisory Role, International Review Committee (IRC): Oncode Institute; Non-Financial Interests, Advisory Role, Scientific Advisory Board (SAB): Oslo University Hospital Comprehensive Cancer Centre (OUH CCC); Non-Financial Interests, Leadership Role, Governance Advisory Committee: European Organization for Research and Treatment of Cancer -EORTC; Non-Financial Interests, Leadership Role, Vice Chairman: World Innovative Networking (WIN) Consortium in Personalized Cancer Medicine; Non-Financial Interests, 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, 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, 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, Other, Coordinating PI. Clinical Trials & Research: Mirati; Non-Financial Interests, Member: AACR, ASCO, EACR, EORTC, SEOM; Other, Other, President: Oncology Master Plan – Catalonia Department of Health; Other, Other, Advisory Committee: Advisory Committee on Pharmaceutical Provision Financing under the Spanish National Health System. A. Vivancos: Financial Interests, Personal, Advisory Board: Roche, Bristol-Myers Squibb, Guardant Health, Bayer, Incyte; Financial Interests, Personal, Stocks/Shares: Reveal Genomics; Financial Interests, Institutional, Research Grant, Preclinical Research Grant: Bristol-Myers Squibb, Roche, Incyte. M.E. Elez Fernandez: Financial Interests, Personal, Advisory Board: Hoffman La - Roche, Bristol-Myers Squibb, Servier, Amgen, Merck Serono, Array Biopharma, Sanofi, Bayer; Financial Interests, Institutional, Research Grant: Hoffman La-Roche, Sanofi Aventis, Amgen, Merck Serono, MSD, Boehringer Ingelheim, AbbVie, Pierre-Fabre, Novartis, Bristol-Myers Squibb, GlaxoSmithKline, Medimmune, Array Pharmaceuticals, AstraZeneca. All other authors have declared no conflicts of interest.