ISM5939 + pembrolizumab

ISM5939 + pembrolizumab is a combination therapy under study for the treatment of advanced and/or metastatic solid tumors. **ISM5939** is an orally administered, highly selective small molecule inhibitor of *ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1)*, developed as a cancer immunotherapy agent. By inhibiting ENPP1, ISM5939 prevents the breakdown of extracellular cyclic GMP-AMP (cGAMP), leading to enhanced activation of the *cGAS-STING* pathway, remodeling the tumor immune microenvironment, increasing cytotoxic immune cell populations, and boosting antitumor immunity[1][2][3][4][6][8]. **Pembrolizumab** is a monoclonal antibody checkpoint inhibitor targeting the *programmed cell death protein 1 (PD-1)* on T cells, blocking immune suppression and enabling robust antitumor immune responses. Preclinical and early clinical studies show that the combination of ISM5939 with pembrolizumab synergistically enhances immune activation, increases M1 macrophage polarization, boosts CD8+ T cell activity, and improves antitumor efficacy in models resistant to PD-1 monotherapy[2][3][4][9]. The combination aims to leverage ISM5939's immunomodulatory effects with pembrolizumab's checkpoint inhibition for superior antitumor activity.

Other names

KeytrudaISM5939ISM-5939ISM 5939