Dr Pavlina Spiliopoulou speaks to ecancer about mRNA-4359, a novel mRNA-based immunotherapy targeting PD-L1 and IDO1, in combination with pembrolizumab as first-line treatment for advanced melanoma.

The combination demonstrated a manageable safety profile, with mostly low-grade treatment-related adverse events.

Dr Spiliopoulou says promising efficacy was observed, with an objective response rate of 83% and disease control in 92% of patients, including complete and partial responses. She highlights that responses were seen regardless of baseline PD-L1 expression.

Translational findings showed consistent induction of antigen-specific T-cell responses and expansion of T-cell receptor clonality, supporting the therapy’s proposed mechanism of action. Baseline tumours exhibited features of an inflamed microenvironment, further aligning with clinical benefit.

Overall, mRNA-4359 plus pembrolizumab shows encouraging early clinical activity and immune engagement in patients with previously untreated advanced melanoma.