ONM-501 + cemiplimab

ONM-501 + cemiplimab is an investigational combination therapy consisting of ONM-501, a dual-activating polyvalent STING (Stimulator of Interferon Genes) agonist, and cemiplimab, a PD-1 immune checkpoint inhibitor monoclonal antibody (marketed as Libtayo). ONM-501 is a pH-sensitive polymer (PC7A) conjugated with cGAMP, forming micelles at physiological pH to protect cGAMP from degradation; in the acidic tumor microenvironment, the micelles release cGAMP intracellularly, resulting in synergistic canonical and noncanonical STING activation, sustained STING signaling, and prolonged immune response. Cemiplimab, an anti-PD-1 antibody, blocks the PD-1 checkpoint and boosts T cell–mediated anti-tumor activity. The combination aims to amplify innate and adaptive anti-tumor immune responses. It is under evaluation in phase 1 clinical trials for advanced solid tumors and lymphomas, including triple negative breast cancer and refractory/relapsed lymphoma.