Abstract 2547
Background
Despite improvements in treatments, the 5-year survival of GEA patients (pts) is disappointing. Individual molecular subtypes display preferential responses to PD-1 blockade. M, an investigational Fc-optimized anti-HER2 monoclonal antibody, is being tested in combination with P in HER2+ GEA post trastuzumab. We present gene expression data from archival FFPE biopsies.
Methods
55 pt samples were assessed by NanoString PanCancer IO360™ assay. Immune signature scores are presented as fold changes (FC) and analyzed by unpaired t-test. Associations examined include baseline IHC PD-L1 (pos vs neg) and HER2 expression (IHC3+ vs 2+), ERBB2 mRNA, inflamed tumor microenvironment (TME), radiographic response, and GC vs GEJ.
Results
ERBB2 mRNA was increased in pts with HER2 IHC3+ vs 2 + (5.6 FC, p < 0.001); IHC3+ was also associated with an inflamed TME (higher IFN-γ signaling, cell proliferation, PD-L2 and inflammatory chemokine expression). ERBB2 expression significantly correlated with response; pts with CR/PR had a 5.13 FC ERBB2 expression compared to PD (p < 0.001). Importantly, ERBB2 expression was associated with anti-tumor activity (ROC-AUC=0.754), with a 3.1 FC between SD/PR/CR vs PD (p = 0.004). TME gene signatures, including PD-1/PD-L1, CTLA4, cytotoxic CD56dim NK cells and DR5 abundance, also trended higher in responders. GC tumors expressed higher levels of ERBB2 (5.25 FC, p < 0.001), with a trend towards a more inflamed TME (higher PD-L1, IFNγ), and had increased clinical response-- this differed from GEJ tumors, which showed lower ERBB2 expression, higher expression of IFITM1, MYC and STAT3, and less clinical responses. Lastly, in PD-L1pos vs PD-L1neg samples, PD-L1 gene expression (1.3 FC, p = 0.013), IFN-γ signaling (1.5 FC, p < 0.001), LAG3 expression (1.4 FC, p = 0.045), IDO1 expression (1.7 FC, p = 0.031), inflammatory chemokines (1.7, p = 0.005), and tumor inflammation signature (1.5 FC, p = 0.0064) were all significantly elevated.
Conclusions
Our study documents for the first time ERBB2 expression and inflamed TME in GEA, which can help differentiate immunologically between GC and GEJ tumors.
Clinical trial identification
NCT02689284.
Editorial acknowledgement
Legal entity responsible for the study
MacroGenics, Inc.
Funding
MacroGenics, Inc.
Disclosure
S. Rutella: Leadership role: Society for Immunotherapy of Cancer; Research grant / Funding (institution): John and Lucille van Geest Foundation. S.E. Church: Shareholder / Stockholder / Stock options, Full / Part-time employment: NanoString Technologies. A.H. Sullivan: Shareholder / Stockholder / Stock options, Full / Part-time employment: NanoString Technologies. S. Warren: Shareholder / Stockholder / Stock options, Full / Part-time employment: NanoString Technologies. J. Baughman: Shareholder / Stockholder / Stock options, Full / Part-time employment: MacroGenics, Inc. J. Muth: Shareholder / Stockholder / Stock options, Full / Part-time employment: MacroGenics, Inc. H. Park: Research grant / Funding (institution): Amgen; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): BeiGene; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): EMD Serono; Research grant / Funding (institution): Gilead Sciences; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Macrogenics; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Medivation; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Millennium; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Puma Biotechnology; Research grant / Funding (institution): Regeneron; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Taiho Pharmaceutical; Research grant / Funding (institution): Vertex. H. Uronis: Shareholder / Stockholder / Stock options, Full / Part-time employment: GeneCentric; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Research grant / Funding (institution): Advaxis; Research grant / Funding (institution): Genentech/Roche; Research grant / Funding (institution): Lycera; Research grant / Funding (institution): Macrogenics. Y. Kang: Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (self): DAE HWA Pharmaceutical; Advisory / Consultancy: Lilly/ImClone; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Ono Pharmaceutical; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Taiho Pharmaceutical; Research grant / Funding (self): LSK Biopharma. M.C.H. Ng: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD Oncology; Honoraria (self), Travel / Accommodation / Expenses: Taiho Pharmaceutical; Advisory / Consultancy: Bristol-Myers Squibb; Research grant / Funding (institution): ASLAN Pharmaceuticals. P. Enzinger: Advisory / Consultancy: Astellas Pharma; Advisory / Consultancy: Five Prime Therapeutics; Advisory / Consultancy: Merck; Advisory / Consultancy: Taiho Pharmaceutical. K.W. Lee: Research grant / Funding (institution): Array BioPharma; Research grant / Funding (institution): ASLAN Pharmaceuticals; Research grant / Funding (institution): AstraZeneca/MedImmune; Research grant / Funding (institution): Five Prime Therapeutics; Research grant / Funding (institution): Green Cross Corp; Research grant / Funding (institution): LSK BioPharma; Research grant / Funding (institution): Macrogenics; Research grant / Funding (institution): Merck KGaA; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Ono Pharmaceutical; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Pharmacyclics. K. Huber: Full / Part-time employment: Macrogenics, Inc. A. Wynter-Horton: Shareholder / Stockholder / Stock options, Full / Part-time employment: MacroGenics, Inc. D. Li: Shareholder / Stockholder / Stock options, Full / Part-time employment: MacroGenics, Inc. Y. Bang: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca/MedImmune; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): BeiGene; Advisory / Consultancy, Research grant / Funding (institution): Green Cross; Advisory / Consultancy: Hanmi; Advisory / Consultancy, Research grant / Funding (institution): Merck Serono; Advisory / Consultancy, Research grant / Funding (institution): MSD Oncology; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Samyang; Advisory / Consultancy, Research grant / Funding (institution): Taiho Pharmaceutical; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Boston Biomedical; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): CKD; Research grant / Funding (institution): Curis; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Five Prime Therapeutics; Research grant / Funding (institution): Genentech/Roche; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Macrogenics; Research grant / Funding (institution): Ono Pharmaceutical; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Takeda. J. Davidson-Moncada: Shareholder / Stockholder / Stock options, Full / Part-time employment: MacroGenics, Inc. D.V. Catenacci: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self): Five Prime Therapeutics; Honoraria (self), Speaker Bureau / Expert testimony: Foundation Medicine; Honoraria (self), Advisory / Consultancy: Genentech/Roche; Honoraria (self): Genmab; Honoraria (self): Gritstone Oncology; Honoraria (self), Speaker Bureau / Expert testimony: Guardant Health; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self): NantOmics; Honoraria (self): OncoPlex Diagnostics; Honoraria (self), Advisory / Consultancy: Taiho Pharmaceuticsal; Advisory / Consultancy: Astellas Pharma. All other authors have declared no conflicts of interest.
Resources from the same session
2152 - Inferring the correlation between incidence rates of melanoma and the average tumor-specific epitope binding ability of HLA class I molecules in different populations
Presenter: Istvan Miklos
Session: Poster Display session 3
Resources:
Abstract
4382 - Thermal Liquid Biopsy as a Valuable Tool in Lung Cancer Screening Programs
Presenter: Alberto Rodrigo
Session: Poster Display session 3
Resources:
Abstract
2465 - Towards a screening test for cancer by circulating DNA analysis
Presenter: Rita Tanos
Session: Poster Display session 3
Resources:
Abstract
3788 - Evaluation of a successful launch of the MammaPrint and BluePrint NGS kit
Presenter: Leonie Delahaye
Session: Poster Display session 3
Resources:
Abstract
3863 - Analysis of prognostic factors on overall survival in elderly women treated for early breast cancer using data mining and machine learning
Presenter: Pierre Heudel
Session: Poster Display session 3
Resources:
Abstract
1993 - Circulating tumor cell detection in epithelial ovarian cancer using dual-component antibodies targeting EpCAM and FRα
Presenter: Na Li
Session: Poster Display session 3
Resources:
Abstract
4281 - CEUS of the breast: Is it feasible in improved performance of BI-RADS evaluation of critical breast lesions?——A multi-center prospective study in China
Presenter: Jun Luo
Session: Poster Display session 3
Resources:
Abstract
2268 - Classification of abnormal findings on ring-type dedicated breast PET for detecting breast cancer
Presenter: Shinsuke Sasada
Session: Poster Display session 3
Resources:
Abstract
4035 - Prediction of benign and malignant breast masses using digital mammograms texture features
Presenter: Cui Yanhua
Session: Poster Display session 3
Resources:
Abstract
5678 - Nanomaterials Augmented LDI-TOF-MS for Hepatocellular Carcinoma Diagnosis and Classification
Presenter: Jian Zhou
Session: Poster Display session 3
Resources:
Abstract