Abstract 126P
Background
Gene expression signatures are predictive biomarkers that explore biological traits from the tumor and its microenvironment (TME). VIGex classifies tumor samples (TS) in 3 categories: Hot (HT), intermediate Cold (IC) and Cold (C) (Hernando-Calvo et al, ESMO2020). Recently, the regulation of HLA I has proven critical for immune response. We aimed to further evaluate the significance of HLA I expression in tumors classified by VIGex.
Methods
Patients with VIGex and HLA I gene expression levels obtained prior to IT were reviewed. An HLA I composite z-score was developed based on gene expression levels of HLA I A, B,C. Response (CR/PR vs PD) was used to categorize HLA I between High and Low (ROC curve, AUC=0.87, CI 95% 0.73-1). Objective response rate (ORR) was defined as per RECIST v.1.1 and clinical benefit rate (CBR) as complete/partial response (CR/PR) or stable disease (SD) for ≥ 4 months (m). Survival were calculated with the Kaplan- Meier method and Hazard Ratio (HR) between HLA I High and Low with Log-rank test.
Results
Out of 198 pts from VHIO pre-screening program between January 2020 and November 2021, 40 pts had VIGex and HLA I analyzed prior to IT. Median age 61.5 years (range 30.4 - 77.36), M: F 23:17, all ECOG 0-1. Tumor types: 19 (47.5%) colorectal cancer 6 (15%) renal cancer, and 15 (37.5%) others. Treatments were Anti PD1/PD-L1 single agent 12 (30%) or IT combinations 28 (70%). Median progression free survival (PFS) was 3.45 m and median overall survival (OS) 26.9 m. VIGex classified 17 pts (42.5%) as HT, 16 (40%) IC and 7 (17.5%) as C. Overall response rate was 53% in HT, 19% in IC and 0% C (p=0.02 two-sided Fisher's exact test). CBR was 70.5% in HT and 39% in IC/C (p=0.002). Among pts categorized as IC, a significantly higher HLA I score was identified in case of clinical benefit to IT (p=0.02 Kruskal-Wallis test). A significantly longer OS was observed for patients with IC/HLA I High as compared to IC/HLA I Low (HR 0.186, (CI 95% 0.046-0.753), p = 0.046).
Conclusions
HLA I gene expression levels may help further segregate outcomes in pts with TS categorized as IC. Whether the HLA I score may add predictive power to already approved IT biomarkers deserves further investigation.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Vall d´Hebron Institute of Oncology.
Disclosure
F.J. Ros Montana: Financial Interests, Institutional, Invited Speaker: Sanofi; Other, Travel and accommodation expenses: Amgen, Pierre Fabre, Merck, Sanofi. I. Baraibar Argota: Financial Interests, Personal, Invited Speaker: Sanofi. C. Suarez Rodriguez: Financial Interests, Personal, Advisory Board: Astellas Pharma, Bayer, Bristol Myers Squibb (Inst), Ipsen, Pfizer S.L.U, Sanofi- Aventis, Hoffmann-La Roche LTD., Merck Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Astellas Pharma, Bristol Myers Squibb (Inst), Ipsen, Pfizer S.L.U, F. Hoffmann-La Roche Ltd.; Financial Interests, Institutional, Funding: Ipsen. I. Brana: Financial Interests, Personal, Advisory Board: Achilles Therapeutics, Bristol Myers Squibb, eTheRNA Immunotherapies, Merck Sharp & Dohme (MSD), Rakuten Pharma, PCI Biotech; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme (MSD), Roche; Financial Interests, Personal, Expert Testimony: Cancer Expert Now, Merck Serono, Boehringer Ingelheim; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Gliknik, Incyte, ISA Pharmaceuticals, Janssen Oncology, Kura, Merck Serono, Debiopharm, Merck Sharp & Dohme (MSD), Nanobiotix, Novartis, Northern Biologics, Regeneron, Pfizer, Seattle Genetics, Shattuck Labs, VCN Biosciences, Roche, Immutep, MacroGenics, Sanofi, PharmaMar, Odonate Therapeutics, Bicycle Therapeutics, Dragonfly therapeutics; Non-Financial Interests, Principal Investigator, Basket of baskets: Cancer Core Europe; Non-Financial Interests, Member, Head and Neck Group: EORTC; Non-Financial Interests, Member: SEOM, ASCO. M.E. Elez Fernandez: Financial Interests, Personal, Advisory Board: F. Hoffman La-Roche, Bristol Myers Squibb, Servier, Amgen, Merck Serono, Array Biopharma, Sanofi, Bayer; Financial Interests, Institutional, Research Grant: F. Hoffman La-Roche, Sanofi Aventis, Amgen, Merck Serono, MSD, Boehringer Ingelheim, AbbVie, Pierre Fabre, Novartis, Bristol Myers Squibb, GlaxoSmithKline, MedImmune, Array Pharmaceuticals, AstraZeneca. E. Felip: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Eli Lilly, Glaxo Smith Kline, Janssen, Merck Sharp & Dohme, Pfizer, Sanofi, Takeda, Merck Serono, Peptomyc, F. Hoffmann-La Roche, Novartis, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Eli Lilly, Medscape, Merck Sharp & Dome, Peervoice, Pfizer, Amgen, F. Hoffmann-La Roche, Janssen, Medical Trends, Merck Serono, Sanofi, Takeda, TouchONCOLOGY; Financial Interests, Institutional, Other, Grant for Oncology Innovation: Merck Healthcare KGaA; Financial Interests, Institutional, Other, Fundación Merck Salud; Financial Interests, Personal, Invited Speaker, Independent member: Grifols; Financial Interests, Institutional, Invited Speaker, Clinical Trial: F. Hoffmann-La Roche Ltd., Merck Sharp & Dohme Corp, AstraZeneca AB, Daiichi Sankyo Inc., Exelixis Inc., Merck KGaA, Janssen Cilag International NV, GlaxoSmithKline Research & Development Limited, AbbVie Deutschland GmbH & Co KG, Novartis Farmaceutica SA, Bayer Consumer Care AG, Takeda Pharmaceuticals International, Boehringer Ingelheim International GmbH, Pfizer S.L.U., Amgen Inc., Bristol Myers Squibb International Corporation (BMS), Mirati Therapeutics Inc.; Non-Financial Interests, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Member, Member of ESMO Nominating Committee and Compliance Committee: ESMO; Non-Financial Interests, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform). E. Garralda: Financial Interests, Personal, Advisory Board: Genentech, F. Hoffmann-La Roche, Neomed Therapeutics1 Inc., Boehringer Ingelheim, Janssen Global Services, Alkermes, Thermo Fisher, MabDiscovery, Anaveon, Lilly, Hengrui; Financial Interests, Personal, Invited Speaker: Ellipses Pharma, Seattle Genetics, Bristol Myers Squibb, MSD, F-Star Therapeutics; Financial Interests, Institutional, Funding: Novartis, Roche, Thermo Fisher, AstraZeneca, Taiho. 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. All other authors have declared no conflicts of interest.