7P - Global ring study determining reproducibility & comparability of CLDN18 testing assays in gastric cancer

Background

Claudin-18.2 (CLDN18.2) the dominant isoform of CLDN18 in gastric tissue is a highly specific tight junction protein of the gastric mucosa expressed in gastric cancer & has emerged as a promising drug target. Zolbetuximab, a monoclonal antibody (Ab) targeting CLDN18.2 is reported to improve progression free & overall survival in combination with chemotherapy in the first-line treatment of CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric (G) & gastroesophageal junction (GEJ) cancers in 2 randomized phase 3 studies. Both studies (SPOTLIGHT, GLOW) met their primary endpoints. Patient selection for CLDN18.2 in these studies used the Ventana CLDN18 (43-14A) assay. It is important in the clinical setting to ensure accurate & reproducible results in the diagnosis of G/GEJ cancer for treatment options. This global ring study was conducted to assess analytical reproducibility & concordance of this assay with 2 other CLDN18 Abs (LSBio LS–B16145-100 & Novus Biologicals NBP2-32002) stained on 3 platforms to confirm possible diagnostic testing methods.

Methods

Tissue microarray (TMA) of 15 gastric cancer samples in triplicate cores was provided to 27 labs across 11 countries. Each lab stained the TMAs using 2-3 CLDN18 Abs with optimized protocols. The TMAs, also stained by the central lab, were used to achieve consensus by expert review. Using agreed scoring algorithms as per the phase 3 studies, IHC scores were generated per core & the results were collated for statistical analysis with the consensus results.

Results

Show high concordance among the 3 Abs across the assessed parameters when performed on each of the 3 platforms, with the highest accuracy & sensitivity observed for Ventana Ab & LSBio Ab across all 3 platforms. Table: 7P

Conclusions

The study shows multiple Abs applied on multiple platforms give highly reproducible and comparable results for detecting CLDN18.2 in gastric cancer providing a potential for their global adoption for CLDN18 testing.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Diaceutics PLC.

Funding

Astellas Pharma.

Disclosure

B. Jasani, A. Dodson, S. Parry, N. Atkey, P. Taniere: Non-Financial Interests, Institutional, Advisory Role, Performing consulting work on behalf of Astellas Pharma in regards to abstract being submitted’: Astellas Pharma. H. Schildhaus: Financial Interests, Institutional, Advisory Board: MSD, BMS, Novartis; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Roche, Takeda, Agilent, ZytoVision; Financial Interests, Personal, Full or part-time Employment: Targos/DLS Inc.; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Funding: Blueprint medicines; Other, Personal, Other, Member of the QuIP Board (Quality Assurance Organisation): QuIP GmbH. S. Clare-Antony: Other, Institutional, Advisory Role, Performing consulting work on behalf of Astellas Pharma in regards to abstract being submitted: Astellas Pharma.