4038 Background: Claudin 18.2 (CLDN18.2), a gastric mucosa tight junction protein, is aberrantly expressed in various cancers. In the FAST Phase 2 trial (NCT01630083), IMAB362, an anti-CLDN18.2 monoclonal antibody, administered in combination with EOX chemotherapy, prolonged survival compared to EOX alone in patients with advanced/recurrent gastric, gastroesophageal junction (GEJ), and esophageal cancers ineligible for trastuzumab. The aim of the present analysis was to assess tumor CLDN18.2 expression and co-expression with HER2 in the FAST population. Methods: Tumor tissue samples from patients screened for inclusion into the FAST trial were analyzed for CLDN18.2 expression using a CE-marked, validated immunohistochemistry (IHC) assay. CLDN18.2 expression was centrally scored based on staining intensity and percentage of stained tumor cells. In a subset of tissue samples with known HER2 status, overall HER2 expression and co-expression with CLDN18.2 were determined. Results: Tissue samples from 730 patients with gastric, GEJ, and esophageal cancer were screened for the FAST study. Of these 730 samples, 685 (94%) were assessed by central IHC; 49% (n=333/685) met the FAST CLDN18.2 expression criterion (≥2+ intensity in ≥40% of tumor cells) for inclusion. Across the 154 tissue samples with known HER2 status, the majority (84%; n=129/154) were HER2–. Furthermore, 94 of these 154 samples (61%) met the FAST CLDN18.2 expression criterion, of which 14% (n=13/94) co-expressed HER2 (Table). Conclusions: In tissue samples from patients screened for the FAST trial, nearly half met CLDN18.2 expression inclusion criterion. In samples with known HER2 status, co-expression of CLDN18.2 and HER2 occurred in 14% of the samples that met study eligibility. These data suggest CLDN18.2 may serve as a non-HER2 overlapping targetable alteration in a distinct subpopulation of patients with gastric, GEJ, or esophageal cancers. Clinical trial information: NCT01630083. [Table: see text]
