DKN-01 + tislelizumab + chemotherapy

This is a **triple combination therapy under investigation** for advanced gastroesophageal adenocarcinoma, consisting of: - **DKN-01**: an investigational humanized immunoglobulin G4 (IgG4) monoclonal antibody targeting and neutralizing Dickkopf-1 (DKK1), a secreted modulator of the Wnt/β-catenin pathway. DKK1 overexpression is linked to tumor progression, poor prognosis, and immune suppression in the tumor microenvironment. DKN-01 aims to interfere with the tumor-promoting and immunosuppressive effects of DKK1. - **Tislelizumab**: an IgG4 monoclonal antibody targeting programmed death-1 (**PD-1**) receptor, functioning as an immune checkpoint inhibitor. It blocks PD-1 interaction with PD-L1/PD-L2, enhancing T-cell-mediated antitumor immune response. - **Chemotherapy (CAPOX or mFOLFOX6)**: standard regimens containing oxaliplatin and fluoropyrimidines, with CAPOX combining capecitabine and oxaliplatin, and mFOLFOX6 combining infusional 5-fluorouracil, leucovorin, and oxaliplatin. The combination was developed to synergistically target tumor cells through **direct cytotoxicity (chemotherapy)**, immune checkpoint inhibition (tislelizumab), and reversal of DKK1-mediated immune suppression (DKN-01). Early-phase clinical trials in metastatic or locally advanced **gastroesophageal adenocarcinoma (GEA)** suggest manageable toxicity and promising efficacy, particularly in patients with high DKK1 expression, and potentially **independent of PD-L1 status**[1][3][5][7].