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ASP2138 + Keytruda (emaretamig + pembrolizumab) is an investigational combination immunotherapy regimen being evaluated for the first-line treatment of claudin 18.2 (CLDN18.2)-positive, HER2-negative locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. The regimen combines emaretamig (ASP2138), a subcutaneously administered bispecific T-cell engager (BiTE) designed to simultaneously bind CLDN18.2 on tumor cells and CD3 on T cells, with pembrolizumab (Keytruda), an intravenously administered anti-PD-1 monoclonal antibody checkpoint inhibitor. By physically bridging T cells to CLDN18.2-expressing tumor cells and blocking the PD-1/PD-L1 inhibitory pathway, the combination aims to synergistically enhance T-cell activation and direct cytotoxic T-lymphocyte-mediated lysis against the tumor cells. The combination is currently being evaluated in a global Phase 3 clinical trial (NCT07673887) in combination with standard chemotherapy (CAPOX or mFOLFOX6).
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