zolbetuximab + pembrolizumab

**Zolbetuximab + pembrolizumab** is a combination therapy under investigation for the treatment of advanced or metastatic gastric and gastroesophageal junction (GEJ) adenocarcinoma that are HER2-negative, Claudin 18.2 (CLDN18.2)-positive, and PD-L1–positive. Zolbetuximab is a chimeric IgG1 monoclonal antibody targeting CLDN18.2, inducing cancer cell death primarily through antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity. Pembrolizumab is a humanized IgG4-kappa monoclonal antibody that inhibits the programmed cell death protein 1 (PD-1) receptor, blocking its interaction with PD-L1/PD-L2 and thus enhancing anti-tumor immune response. The combination aims to exploit complementary mechanisms—direct tumor cell killing by zolbetuximab and immune checkpoint inhibition by pembrolizumab—for synergistic antitumor activity. Primary indication under study is advanced/metastatic gastric or GEJ cancer with relevant biomarker positivity[1][3][4][5][6].