CLDN18.2 expression

It is currently a clinically relevant predictor for adenocarcinomas of the stomach and the gastroesophageal junction, although its use will likely extend also to other diagnoses. The aim of this report is to provide an overview of selected aspects of CLDN18.2 expression testing, including the choice of appropriate tissue, the issue of tumor heterogeneity, antibodies suitable for testing and their evaluation, where such testing can be performed, and the prospects for the future.

The approved antibody zolbetuximab requires higher expression levels (≥75% of tumor cells with 2-3+ membranous staining), yet broader thresholds are increasingly explored...Broadening the threshold for positivity identified nearly three-quarters of patients as CLDN18.2 positive, underscoring the impact of selection cut points on trial eligibility. These findings highlight the potential to expand patient access to CLDN18.2-targeted therapies using lower thresholds.

In the remaining HER2 cohort, CLDN18.2-positive patients had shorter PFS (3.2 versus 8.0 months, HR 3.40, 95% CI 1.38-8.40, P = 0.008) and OS (7.1 versus 12.9 months, HR 2.44, 95% CI 1.04-5.74, P = 0.041). CLDN18.2 positivity may attenuate the efficacy of T-DXd in HER2-positive mGC/GEJC, supporting the rationale for dual blockade of CLDN18.2 and HER2.

P1/2, N=150, Recruiting, Astellas Pharma Global Development, Inc. | Not yet recruiting --> Recruiting

P3, N=572, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting

In this study, we demonstrated that IBI389 effectively redirects T cells to CLDN18.2-expressing tumors, suppresses tumor growth, and synergizes with PD-1 blockade and has a favorable safety profile. By virtue of its ability to enhance immune infiltration, remodel cytokine responses, and reduce tumor-immune spatial separation, IBI389 may have considerable potential as a novel therapeutic strategy for CLDN18.2-positive gastric cancer and related malignancies.

This single-center retrospective analysis utilized prospectively collected data from 72 patients treated with FOLFIRINOX (59.7%) or gemcitabine plus nab-paclitaxel (40.3%)...These findings indicate the potential prognostic value of integrating molecular and systemic biomarkers in unresectable PDAC. However, due to the retrospective design and limited sample size, these results should be regarded as hypothesis-generating and necessitate validation in larger, independent cohorts prior to clinical implementation.

The developed 1⁸F-FDG PET/CT-based multimodal radiomics model serves as an effective, non-invasive tool for predicting CLDN18.2 expression in GAC. The study validates the hypometabolic nature of CLDN18.2-positive tumors, suggesting this radiomics approach can effectively complement traditional biopsy methods for patient stratification.

P1, N=160, Recruiting, SystImmune Inc. | N=120 --> 160

P1/2, N=150, Not yet recruiting, Astellas Pharma Global Development, Inc.

P2, N=90, Not yet recruiting, Innovent Biologics (Suzhou) Co. Ltd.

P2, N=33, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting