What are the key biomarkers?

In advanced/metastatic gastric cancer and gastroesophageal junction/esophageal adenocarcinoma

Guidelines recommend testing for key biomarkers3-7

National Comprehensive Cancer Network® (NCCN®) and ASCO® recommend testing for3-5:

CLDN18.23,4

Clinically Relevant Threshold:

≥75% viable tumor cells with moderate to strong membrane CLDN18.2 staining (2+/3+ intensity by IHC)

HER23,4

Clinically Relevant Threshold:

IHC 3+ or IHC 2+/ISH positive*

MSI/MMR3,4

Determined by:

PCR/NGS for MSI and IHC for MMR

PD-L13,4,8-10

Clinically Relevant Threshold:

CPS ≥1

*

The NCCN Guidelines Panel recommends that HER2 IHC testing be ordered/performed first, followed by ISH methods in cases showing 2+ (equivocal) expression by IHC.3,4

NCCN=National Comprehensive Cancer Network® (NCCN®).

How do current treatment options fall short?

In advanced/metastatic gastric cancer and gastroesophageal junction/esophageal adenocarcinoma (GC/GEJC/EAC)

Despite recent advances in biomarker-directed therapies, chemotherapy-containing regimens remain a cornerstone of 2L+ treatment 3,4,11

Current outcomes are poor

2L Median OS:

9 Months9 Months11,12†

3L+ Median OS:

6 Months6 Months11,13‡
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There is an urgent need to improve upon CURRENT STANDARDS OF CARE for these patients

†

Based on 2 data sets: (1) 330 patients with 2L+ advanced/metastatic GC/GEJC treated with combination targeted therapy + chemotherapy regimen with a median OS of 9.6 months. (2) Flatiron Health aggregated data for 436 patients with 2L advanced/metastatic GC/GEJC/EAC treated with chemotherapy combinations, including combinations with targeted therapy or immunotherapies, or immunotherapy alone with a median OS of 8.2 months.11,12

‡

Based on 2 data sets: (1) 337 patients with 3L+ advanced/metastatic GC/GEJC treated with chemotherapy with a median OS of 5.7 months. (2) Flatiron Health aggregated data for 157 patients with 3L advanced/metastatic GC/GEJC/EAC treated with chemotherapy combinations, including combinations with targeted therapy or immunotherapies, or immunotherapy alone with a median OS of 5.7 months.11,13

What do we know about CLDN18.2?

CLDN18.2 is an actionable and highly prevalent biomarker in advanced/metastatic GC/GEJC/EAC14,15

Many patients are still not being tested for CLDN18.216

~40% of patients WERE tested for CLDN18.2 IN A RECENT REAL-WORLD ANALYSIS16§

Up to 8 in 10 patients have tumors that express CLDN18.2 at some level and intensity by IHC14,15

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And yet

most-patients

did not meet the current threshold for CLDN18.2 "positivity" (≥75% expression, 2+ or 3+ intensity by IHC) in a recent real-world analysis16§

§

Based on Flatiron Health data set of 11,099 patients who were diagnosed with advanced/metastatic GC/GEJC since 2016. For the 1220 patients who were diagnosed after the FDA approval of a CLDN18.2-targeted therapy in October 2024, the CLDN18.2 testing rate was 39.5%. Of the patients who were tested for CLDN18.2 across the full study period, 42.6% were considered positive (473/1109).16

Get the precise level

Dig Deeper to Discover Meaning of CLDN18.2

IN ADVANCED/METASTATIC GC/GEJC/EAC

DISCOVER THE DEEPER MEANING OF PRECISE EXPRESSION

Know your patients’ specific CLDN18.2 expression level and staining intensity by IHC1,2

There is an urgent need to improve upon CURRENT STANDARDS OF CARE

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AstraZeneca is following the science to explore ways to help patients with advanced/metastatic GC/GEJC/EAC

2L=second line; 3L=third line; ASCO=American Society of Clinical Oncology; CPS=Combined Positive Score; EAC=esophageal adenocarcinoma; FDA=US Food and Drug Administration; GC=gastric cancer; GEJC=gastroesophageal junction cancer; HER2=human epidermal growth factor receptor 2; IHC=immunohistochemistry; ISH=in situ hybridization; MMR=mismatch repair; MSI=microsatellite instability; NGS=next-generation sequencing; OS=overall survival; PCR=polymerase chain reaction; PD-L1=programmed death-ligand 1.

References: 1. Alami Idrissi Y, Zatsepina A, Saeed A. Claudin 18.2 in gastroesophageal adenocarcinoma: prevalence, biomarker associations, and implications for equity. J Gastrointest Oncol. 2025;16(6):2891-2894. 2. Wallam S, Park J, Wu LW, Moy RH. Retrospective analysis of Claudin18.2 expression in ethnically diverse patients with gastroesophageal adenocarcinoma. J Gastrointest Oncol. 2025;16(4):1420-1433. 3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Gastric Cancer V.4.2026. © National Comprehensive Cancer Network, Inc. 2026. All rights reserved. Accessed September 16, 2026. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Esophageal and Esophagogastric Junction Cancers V.4.2026. © National Comprehensive Cancer Network, Inc. 2026. All rights reserved. Accessed September 16, 2026. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 5. Shah MA, Kennedy EB, Deighton D, et al. Immunotherapy and targeted therapy for advanced gastroesophageal cancer: ASCO Guideline Update. J Clin Oncol. 2026;44(12):1145-1165. 6. Wang FH, Zhang XT, Tang L, et al. The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2023. Cancer Commun (Lond). 2024;44(1):127-172. 7. Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2025 (7th edition). Gastric Cancer. 2026;29(2):271-299. 8. Mastracci L, Grillo F, Parente P, et al. PD-L1 evaluation in the gastrointestinal tract: from biological rationale to its clinical application. Pathologica. 2022;114(5):352-364. 9. Knief J, Lazar-Karsten P, Hummel R, Wellner U, Thorns C. PD-L1 expression in carcinoma of the esophagogastric junction is positively correlated with T-cell infiltration and overall survival. Pathol Res Pract. 2019;215(6):152402. 10. Kulangara K, Zhang N, Corigliano E, et al. Clinical utility of the combined positive score for programmed death ligand-1 expression and the approval of pembrolizumab for treatment of gastric cancer. Arch Pathol Lab Med. 2019;143(3):330-337. 11. Shah MA, Shah A, Luo L, et al. REPERTOIRE: Real-world treatment patterns and outcomes in US patients with HER2-negative advanced gastric, gastroesophageal junction and esophageal adenocarcinoma. Poster presented at: ASCO Gastrointestinal Cancers Symposium; January 8-10, 2026; San Francisco, CA. Poster 306. 12. Wilke H, Muro K, Van Cutsem E, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014;15(11):1224-1235. 13. Shitara K, Doi T, Dvorkin M, et al. Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2018;19(11):1437-1448. 14. Maeng CH, Alkashash A, Sy A, et al. Clinicopathologic correlates of claudin 18.2 expression in esophagogastric cancer at multiple expression levels. ESMO Gastrointest Oncol. 2026;11:100278. 15. Cao W, Xing H, Li Y, et al. Claudin18.2 is a novel molecular biomarker for tumor-targeted immunotherapy. Biomark Res. 2022;10(1):38. 16. Zhang Y, Radi O, Wang X, et al. Real-world adoption and sequencing of CLDN18.2, PD-L1, and HER2 testing in advanced gastric and gastroesophageal junction adenocarcinoma. Poster presented at: American Society of Clinical Oncology Annual Meeting; May 29-June 2, 2026; Chicago, IL. Poster 4035.

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