trabectedin + irinotecan

Trabectedin + irinotecan is an investigational combination therapy consisting of two small molecule chemotherapeutic agents: trabectedin, a marine-derived DNA minor groove binder that disrupts transcription factor activity and modulates the tumor microenvironment, and irinotecan, a topoisomerase I inhibitor. Preclinical studies have shown that trabectedin can suppress oncogenic drivers such as EWS::FLI1 in Ewing sarcoma, with this effect potentiated by subsequent administration of low-dose irinotecan. The combination has demonstrated synergistic antitumor activity in preclinical models and early-phase clinical trials for relapsed or refractory Ewing sarcoma (ES) and desmoplastic small round cell tumor (DSRCT), leading to meaningful clinical benefit including disease stabilization and occasional complete responses. The regimen is under investigation primarily for translocation-positive sarcomas, especially those harboring the EWS::FLI1 fusion transcript[1][2][3][4][6].