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Target Overview
Claudin 18.2 (CLDN18.2), an essential component of tight junctions in gastric epithelium, is highly expressed in gastric, pancreatic and esophageal adenocarcinoma.1 CLDN18.2 is a validated therapeutic target in CLDN18.2-high gastric cancer.2-4
Compound Overview
AZD5863 is a CLDN18.2- and CD3-targeting T cell engager designed with bivalent high-affinity binding to CLDN18.2 and monovalent low-affinity binding to CD3 to reduce class-associated toxicities (eg, CRS), while maintaining potent and specific antitumor activity. AZD5863 has been demonstrated to induce T cell mediated killing of CLDN18.2 expressing cells of gastric, pancreatic and esophageal cancer origin in in vitro and in vivo models, and to induce bystander killing of neighboring CLDN18.2 negative cells, expanding its use to a wider patient population.5
Mechanism of Action
References
1. Sahin U, Koslowski M, Dhaene K, et al. Clin Cancer Res. 2008;14(23):7624-7634. 2. Shitara K, Lordick F, Bang YJ, et al. Lancet. 2023;401(10389):1655-1668. 3. Shah MA, Shitara K, Ajani JA, et al. Nat Med. 2023;29(8):2133-2141. 4. Xu RH, Ruan DY, Zhang DS, et al. J Clin Oncol. 2023;41:434420-434420. 5. Gaspar M, Natoli M, Castan L, et al. J Immunother Cancer. 2023;11:1288-1288.
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Abbreviations
CLDN18.2
claudin 18.2
CD3
cluster of differentiation 3
CRS
cytokine release syndrome
GC
gastric cancer
GEJC
gastroesophageal junction cancer
PDAC
pancreatic ductal adenocarcinoma
Target Overview
Claudin 18.2 (CLDN18.2), an essential component of tight junctions in gastric epithelium, is highly expressed in gastric, pancreatic and esophageal adenocarcinoma.1 CLDN18.2 is a validated therapeutic target in CLDN18.2-high gastric cancer.2-4
Compound Overview
AZD5863 is a CLDN18.2- and CD3-targeting T cell engager designed with bivalent high-affinity binding to CLDN18.2 and monovalent low-affinity binding to CD3 to reduce class-associated toxicities (eg, CRS), while maintaining potent and specific antitumor activity. AZD5863 has been demonstrated to induce T cell mediated killing of CLDN18.2 expressing cells of gastric, pancreatic and esophageal cancer origin in in vitro and in vivo models, and to induce bystander killing of neighboring CLDN18.2 negative cells, expanding its use to a wider patient population.5
Mechanism of Action
References
1. Sahin U, Koslowski M, Dhaene K, et al. Clin Cancer Res. 2008;14(23):7624-7634. 2. Shitara K, Lordick F, Bang YJ, et al. Lancet. 2023;401(10389):1655-1668. 3. Shah MA, Shitara K, Ajani JA, et al. Nat Med. 2023;29(8):2133-2141. 4. Xu RH, Ruan DY, Zhang DS, et al. J Clin Oncol. 2023;41:434420-434420. 5. Gaspar M, Natoli M, Castan L, et al. J Immunother Cancer. 2023;11:1288-1288.
Clinical trial information
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Abbreviations
CLDN18.2
claudin 18.2
CD3
cluster of differentiation 3
CRS
cytokine release syndrome
GC
gastric cancer
GEJC
gastroesophageal junction cancer
PDAC
pancreatic ductal adenocarcinoma