monalizumab + cetuximab + anti-PD(L)1

A combination regimen consisting of **monalizumab** (a first-in-class humanized IgG4 monoclonal antibody immune checkpoint inhibitor targeting NKG2A receptors on CD8+ T cells and NK cells), **cetuximab** (a chimeric IgG1 monoclonal antibody targeting the epidermal growth factor receptor/EGFR, which also mediates antibody-dependent cell-mediated cytotoxicity or ADCC), and an **anti-PD-(L)1** antibody (such as nivolumab, pembrolizumab, or durvalumab, which block the programmed cell death-1 (PD-1) or programmed death-ligand 1 (PD-L1) checkpoint to restore immune cell activity). This combination aims to enhance anti-tumor responses by simultaneously removing several distinct brakes on the immune system and increasing both innate and adaptive immunity against tumor cells. Clinical trials have focused particularly on heavily pretreated recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) after failure of platinum, cetuximab, and anti-PD-(L)1 therapies, a population with high unmet medical need. Monalizumab is developed by Innate Pharma, cetuximab by Eli Lilly (ImClone) and Merck KGaA. Anti-PD-(L)1 antibodies are developed by multiple companies including Bristol Myers Squibb (nivolumab), Merck (pembrolizumab), and AstraZeneca (durvalumab). This combination is under investigation in clinical trials, usually with intravenous administration.[1][3][5]