mRNA-2416 + durvalumab

mRNA-2416 + durvalumab is an investigational combination immunotherapy composed of two agents: mRNA-2416, a lipid nanoparticle-encapsulated messenger RNA encoding human OX40 ligand (OX40L) administered by intratumoral injection, and durvalumab, a programmed death ligand-1 (PD-L1) blocking monoclonal antibody given intravenously. mRNA-2416 is designed to locally generate OX40L in the injected tumor microenvironment, enhancing T-cell mediated antitumor immunity. Durvalumab acts as an immune checkpoint inhibitor, aiming to augment and sustain antitumor immune responses initiated by OX40L expression. This combination has been evaluated in a phase I/II clinical study for patients with relapsed or refractory advanced solid tumors and ovarian cancer, but primary efficacy endpoints were not met and the trial was terminated. Mechanistically, the regimen increases local OX40L, induces proinflammatory gene expression, increases intratumoral T cells, and heightens systemic cytokine responses, with a safety profile similar to other OX40 pathway therapies[1][2][3][7].