The VENTANA CLDN18 (43-14A) RxDx Assay is the first immunohistochemistry (IHC) assay CE-IVDR approved to identify patients with gastric or GEJ adenocarcinoma who are eligible for CLDN18.2-targeted treatment with VYLOY™ (zolbetuximab).1
Gastric cancer is the 5th most common cancer and the 5th leading cause of cancer deaths worldwide2. In the EU, the overall survival rate of gastric cancer patients is 25%3, whilst the five-year survival rate for metastatic gastric patients is only 3%.4 Even though incidence of gastric cancer has been declining in Western Europe5, some of the highest rates are observed in Central and Eastern Europe2.
CLDN18 belongs to the claudin protein superfamily.8 Claudins are tetramembrane proteins with two extracellular loops and the intracellular N- and C-termini regions in the cytoplasm.8,9 CLDN18 is expressed as two protein isoforms: CLDN18.1 and CLDN18.2.8,9
CLDN18.1 is predominantly expressed in normal and neoplastic lung tissue.8,9 CLDN18.2 is only expressed in differentiated epithelial cells of the gastric mucosa and not in other healthy tissues under normal physiological conditions.8,9,10 Under malignant transformation, CLDN18.2 is frequently retained in gastric cancer and its metastases, and may be expressed in other neoplastic tissues (e.g. pancreas, lung, ovary).8,9,10
The primary antibody used in the VENTANA CLDN18 (43-14A) RxDx Assay detects both isoforms of the CLDN18 protein while the therapy, zolbetuximab, is a monoclonal antibody that binds specifically to CLDN18.2 on tumor cell membranes.11 However, CLDN18.2 is the predominant isoform expressed in gastric and pancreatic cancers so it is understood that most if not all protein measured by the VENTANA CLDN18 (43-14A) RxDx Assay in gastric/GEJ indications is CLDN18.2.12 This makes the VENTANA CLDN18 (43-14A) RxDx Assay the only current candidate for identifying a previously undefined subset of patients that may now benefit from zolbetuximab.
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