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Abstract Background: Claudin18. 2 (CLDN18. 2) is a tight junction protein highly specific to gastric mucosa, and a validated target for gastric cancer (GC) treatment. Immune checkpoint therapy targeting PD-1 combined with chemotherapy has been approved as the first line therapy of GC. Understanding the expression profiles of CLDN18. 2 and PD-L1 could guide the development of combination therapies to maximize the benefits of these two agents. This study investigated the prevalence of CLDN18. 2 expression in gastric/gastroesophageal junction adenocarcinoma (G/GEJC) screening samples from studies Transtar101 (NCT04396821 in US) and TranStar102 (NCT04495296 in China), and its correlation with various clinical characteristics and PD-L1 expression. Methods: CLDN18. 2 expression in formalin-fixed, paraffin-embedded (FFPE) G/GEJC tissue samples was prospectively detected by an immunohistochemistry-based LDT using an in-house anti-CLDN18. 2 antibody (Clone14G11) on the Leica Bond III stainer. CLDN18. 2 expression was assessed by scoring the staining intensity (0, 1+, 2+, 3+) and the percentage of positive tumor cells. Positive CLDN18. 2 expression is defined as the cutoff at ≥10% of tumor cell with ≥1+ staining intensity for this evaluation. PD-L1 expression was assessed by combined positive score (CPS) using Agilent’s PD-L1 IHC 28-8 pharmDx. Both assays were conducted in CAP/CLIA certified LabCorp central lab. Results: 547 G/GEJC patient samples had CLDN18. 2 results as part of the screening procedures for the clinical trials. Of these patients (454 GC/93 GEJC), 439 (80%) were Asian, 29 (5%) were Caucasian, 2 (0. 4%) were other ethnic group, and 77 (14%) were not recorded; 434 (79%) were primary tumors and 113 (21%) were metastasis; 201 (37%) were core needle biopsies (CNB), 108 (20%) were surgical resections (SR) and 238 (44%) had no information. 311 (57%) samples had positive CLDN18. 2 expressions (≥10%/≥1+). No significant difference in CLDN18. 2 positive rates were found between TranStar101 and TranStar102 studies (p=0. 801), Asian and Caucasian (p=0. 612), GC and GEJC (p=0. 373), primary and metastatic specimens (p=0. 055) or CNBs and SRs (p=0. 715). Out of 83 TranStar102 specimens that had both CLDN18. 2 and PD-L1 results, 15 (18%) had PD-L1 CPS≥5, 59 (71%) had positive CLDN18. 2, and 10 (15%) had both positive CLDN18. 2 and PD-L1 CPS≥5. No correlation (p=0. 393) was observed between PD-L1 scores (CPS5 or CPS≥5) and CLDN18. 2 expression (≥10%/≥1+ or 10%/≥1+). Conclusions: Data suggested CLDN18. 2 expression levels were independent of PD-L1 status, and support the use of Transcenta 14G11 antibody for CLDN18. 2 detection regardless of sample collection methods, location, and patient demographics. An anti-CLDN18. 2 companion diagnostic device based on 14G11 is being developed (CLDN18. 2 IHC 14G11 pharmDx, Agilent Technologies, Inc. ). Citation Format: Li Shen, Carol Mao, Alan Lin, Ying Gu, Jenny Milata, Lijuan Zhang, Chuan Qi, Jenny Yao, Steven Yu, Changjun Yue, Lin Shen, Yelena Janjigian, Xueming Qian, Wen-I Chang, Caroline Germa. Prevalence of claudin18. 2 expression in gastric/gastroesophageal junction adenocarcinoma among patients in TranStar101 and TranStar102 clinical trials abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 3629.
Shen et al. (2024) studied this question.