Cosibelimab for advanced cutaneous squamous cell carcinoma: pharmacological rationale and clinical evidence

INTRODUCTION: Immune checkpoint inhibition has transformed the management of advanced cutaneous squamous cell carcinoma (cSCC). Cosibelimab is a fully human IgG1 monoclonal antibody targeting PD-L1 and the first PD-L1 inhibitor approved for advanced cSCC. Uniquely cosibelimab preserves PD-L2-PD-1 signaling and retains an intact Fc domain capable of mediating antibody-dependent cellular cytotoxicity, providing potential mechanistic differentiation from existing therapies. AREAS COVERED: This review examines the pharmacodynamic and pharmacokinetic properties of cosibelimab and evaluates its clinical efficacy and safety in advanced cSCC. Available evidence is contextualized against established PD-1 inhibitors, particularly cemiplimab and pembrolizumab, with consideration of comparative efficacy, immune-related toxicity, limitations of cross-trial comparisons and potential future applications of cosibelimab. EXPERT OPINION: Cosibelimab provides an effective additional immunotherapeutic option for advanced cSCC, with clinical activity broadly comparable to established PD-1 inhibitors. Its distinct pharmacology and numerically low incidence of severe immune-related toxicity are of particular interest. Its current evidence base is limited by single-arm studies, relatively immature survival data and the absence of evidence in earlier-stage cSCC. Mature follow-up, real-world evidence and prospective studies are required to determine whether its pharmacological distinctions translate into meaningful clinical advantages and to define its optimal position within the evolving cSCC treatment landscape.