margetuximab + tebotelimab

Margetuximab + tebotelimab is an investigational combination therapy for HER2-positive advanced solid tumors and gastroesophageal cancers. Margetuximab is an Fc-engineered monoclonal antibody targeting the human epidermal growth factor receptor 2 (HER2), designed to enhance immune-mediated tumor cell killing by increasing affinity for activating Fcγ receptors on immune effector cells. Tebotelimab is a bispecific tetravalent DART® protein that simultaneously targets programmed cell death protein 1 (PD-1) and lymphocyte activation gene-3 (LAG-3), both of which are immune checkpoint molecules that suppress T-cell function. The combination aims to enhance anti-tumor immunity by blocking HER2 signaling and releasing T-cell inhibition via dual checkpoint blockade. This regimen has been evaluated in phase 1–3 clinical trials for patients with HER2-positive relapsed/refractory advanced solid tumors, including gastric cancer and gastroesophageal junction cancer[1][4][5].