VENTANA® CLDN18 (43-14A) RxDx Assay
First IHC companion diagnostic for determining claudin 18 (CLDN18) protein expression in patients with gastric or gastroesophageal junction (GEJ) adenocarcinoma who may benefit from VYLOY™ (zolbetuximab)1
The VENTANA CLDN18 (43-14A) RxDx Assay is the first immunohistochemistry (IHC) assay FDA 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 4th leading cause of cancer deaths worldwide.2 Gastric/GEJ cancer is less prevalent in the US than in other parts of the world; however, it is often diagnosed late as signs and symptoms are common to other conditions.3 In the US, 62% of gastric/GEJ cases are advanced when initially diagnosed, contributing to a 5-year overall survival rate of only 6%.4,5
CLDN18.2 serves as a predictive biomarker for the likelihood of response to CLDN18.2-targeted therapy for patients with gastric cancer including GEJ6,7
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.
References
- Roche. VENTANA CLDN18 (43-14A) RxDx Assay, US Package Insert. 2023.
- Sung H et al. CA Cancer J Clin 2021;71:209-49.
- 3. National Cancer Institute. Gastric Cancer Treatment (PDQ®)-Patient Version. https://www.cancer.gov/types/stomach/patient/stomach- treatment-pdq. Accessed March 8, 2023.
- American Cancer Society. Cancer Facts & Figures 2022. https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2022.html. Accessed October 3, 2023.
- NCI SEER Cancer stat facts: stomach cancer. https://seer.cancer.gov/statfacts/html/stomach.html. Accessed October 3, 2023.
- Sahin U, Koslowski M, Dhaene K, et al. Claudin-18 splice variant 2 is a pan-cancer target suitable for therapeutic antibody development. Clin Cancer Res 2008;14(23):7624-34.
- Saito T, Matsuda T, Moran D. ESMO World Congress on Gastrointestinal Cancer. Virtual. Poster #286. 2021.
- Hashimoto I, Oshima T. Claudins and gastric cancer: An overview. Cancers (Basel). 2022;14(2):290.
- Singh P, Toom S, Huang Y. Anti-Claudin 18.2 antibody as new targeted therapy for advanced gastric cancer. J Hematol Oncol. 2017;10(1):105. 10.
- Selim JH, Shaheen S, Sheu WC, et al. Targeted and novel therapy in advanced gastric cancer. Exp Hematol Oncol. 2019; 8:25.
- Lo Nigro C, Macagno M, Sangiolo D, Bertolaccini L, Aglietta M, Merlano MC. Ann Transl Med. 2019 Mar;7(5):105.
- T. Saito, T. Matsuda, D. Moran, P-114 Claudin 18 isoform expression in gastric adenocarcinoma and pancreatic adenocarcinoma, Annals of Oncology, Volume 32, Supplement 3, 2021, Page S138, ISSN 0923-7534, https://doi.org/10.1016/j.annonc.2021.05.169.
