Abstract 2535: Development of Claudin 18.2 IHC 14G11 pharmDx as a clinical trial assay for the clinical development of anti-claudin 18.2 monoclonal antibody osemitamab (TST001) in gastric and gastroesophageal junction adenocarcinoma
Authors: Alderson Hayley , Lefley Katie , Fregoso Lesly , Bharadwaj Achintya , Castellanos-McKenney Dan , Tabuena-Frolli Siena , Kell Donna , Yao Xinlai , Qian Xueming , Xu Li , Germa Caroline , Oroudjev Emin 
Published: March 2024

Abstract
Clone 14G11 is a mouse anti-Claudin 18.2 monoclonal antibody developed by Transcenta. The antibody was generated against a linear epitope located on the extracellular domain of loop1 and has a binding site that overlaps with the binding site of therapeutic antibody Osemitamab. It was selected to further develop for the detection of Claudin 18.2 expression in human cancer. Agilent Technologies, Inc. is developing Claudin 18.2 IHC 14G11 pharmDx as an immunohistochemical (IHC) assay for the detection of Claudin 18.2 protein in gastric and gastroesophageal junction (GEJ) adenocarcinoma in support of clinical studies conducted by Transcenta Therapeutics. Analytical verification for Claudin 18.2 IHC 14G11 pharmDx included sensitivity, specificity, and precision assessment. Testing was performed on human formalin-fixed, paraffin-embedded (FFPE) gastric and GEJ tissues using Autostainer Link 48 with EnVision FLEX visualization system. Biomarker expression was evaluated using Tumor Proportion Score (TPS). TPS is defined as the percentage of viable invasive tumor cells that exhibit convincing partial or complete membrane staining at any intensity. Sensitivity testing of 102 commercially procured FFPE gastric/GEJ specimens demonstrated a broad dynamic range of Claudin 18.2 positivity that covered TPS from 0% to 100%. Specificity tests confirmed specific targeting of the Claudin 18.2 protein in a variety of normal and abnormal tissues. For laboratory precision testing, which evaluated the assay variability in relation to run, instrument, operator, and reagent lot, ≥ 95% of TPS values were within expected variability limits for each parameter. For observer precision testing, two-sided 95% confidence intervals were ≥ 85% for negative, positive, and overall agreements when assessing two clinical cutoffs. These results demonstrated the Claudin 18.2 IHC 14G11 pharmDx assay can provide reliable and reproducible results in day-to-day testing. Analytical verification testing indicates Claudin 18.2 IHC 14G11 pharmDx is a sensitive, specific, and precise assay for detecting Claudin 18.2 in gastric and GEJ adenocarcinoma. Claudin 18.2 IHC 14G11 pharmDx for Investigational Use Only/for Performance Evaluation Only will be used for patient selection in the upcoming phase III trial of gastric/GEJ adenocarcinoma where applicable ethics committee and regulatory approvals have been granted.
Citation Format: Hayley Alderson, Katie Lefley, Lesly Fregoso, Achintya Bharadwaj, Dan Castellanos-McKenney, Siena Tabuena-Frolli, Donna Kell, Xinlai Yao, Xueming Qian, Li Xu, Caroline Germa, Emin Oroudjev. Development of Claudin 18.2 IHC 14G11 pharmDx as a clinical trial assay for the clinical development of anti-claudin 18.2 monoclonal antibody osemitamab (TST001) in gastric and gastroesophageal junction adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2535.