CLDN18.2 expression

In conclusion, CLDN18.2-positive colorectal adenocarcinomas are frequently MMR deficient, BRAF V600E mutated, and demonstrate distinct histologic features. Future studies addressing the efficacy of zolbetuximab therapy in this subset of colorectal cancers are needed.

P1/2, N=44, Terminated, SOTIO Biotech a.s. | N=160 --> 44 | Trial completion date: Jun 2028 --> Dec 2024 | Recruiting --> Terminated | Trial primary completion date: Dec 2027 --> Dec 2024; Trial terminated by Sponsor based on benefit- risk reassessment

P2, N=64, Not yet recruiting, Zhejiang University

The present study suggests that a subset of patients with CCA exhibited a marked expression of CLDN18.2. These findings underline the need to perform a clinical study evaluating the efficacy of anti-CLDN18.2 therapy in patients suffering from CCA.

Approximately 2% of all CRC cases in this study were CLDN18.2 positive and had unfavorable features (e.g., mucinous or poorly differentiated adenocarcinoma, T3-4 disease, lymphatic invasion, BRAF V600E mutation) and deficient MMR status. CLDN18.2 positivity did not have a significant impact on RFS or OS.

Trastuzumab with chemotherapy is the standard regimen for HER2-positive GC/GEJC. While, for HER2-negative cases, chemotherapy with or without immune checkpoint inhibitors (ICIs)such as nivolumab or pembrolizumab are regarded as the standard therapy...We will highlight the previous clinical trials of zolbetuximab and provide future perspective of CLDN18.2 targeted therapy. In addition, we will introduce the ongoing development of various CLDN18.2 targeting therapies such as newer monoclonal antibodies, antibody-drug conjugates(ADCs), chimeric antigen receptor T-cell(CAR- T)therapy, and bispecific antibodies.

Characterizing unresectable, metastatic, or recurrent GC with positive CLDN18.2 expression and evaluating intratumoral heterogeneity and prognostic implications of various therapeutics help advance treatment strategies and develop new therapies for patients with GC.

Question The study resolves the clinical issue of determining the correlation between [18F]FDG PET/CT imaging and claudin 18.2 expression in metastatic gastric cancer. Findings Claudin 18.2-positive metastatic gastric cancers exhibit relatively lower [18F]FDG uptake than negative ones. The SUVmax of 10.9 moderately predicts claudin 18.2 expression. Clinical relevance [18F]FDG PET/CT imaging could be a noninvasive way to predict claudin 18.2 status in metastatic gastric cancer, helping to improve personalized treatment plans.

Additionally, low CLDN18.2 expression was linked to favorable prognosis. Our study reveals the potential value of CLDN18.2 for tumor prognosis and targeted therapy in various cancers, especially upper gastrointestinal tract cancers.

P2, N=143, Active, not recruiting, Astellas Pharma Global Development, Inc. | Recruiting --> Active, not recruiting

P1, N=12, Completed, Innovent Biologics (Suzhou) Co. Ltd. | Recruiting --> Completed | Phase classification: P1a/1b --> P1 | N=48 --> 12

CLDN18.2-TAC T cells effectively eradicated established tumor xenografts in mice in the absence of observed off-target or on-target/off-tumor effects, elicited durable efficacy in recursive killing and tumor rechallenge experiments, and remained unreactive in coculture with human cells representing vital organs. Thus, the data demonstrate that CLDN18.2-TAC T cells can induce a specific and long-lasting anti-tumor response in various CLDN18.2-positive solid tumor models without notable TAC-dependent toxicities, supporting the clinical development of TAC01-CLDN18.2.