Phase 1/2 PM54 oncogenic transcription inhibitor + irinotecan/doxorubicin

PharmaMar’s Phase 1/2 open-label, non-randomized master combination study tests PM54, an ecteinascidin-family transcription inhibitor that binds DNA and disrupts oncogenic transcription through RNA polymerase II inhibition, with two backbone chemotherapies: irinotecan (topoisomerase I inhibitor) and doxorubicin (anthracycline DNA-intercalating/topoisomerase II–inhibiting chemotherapy). Each pairing runs a dose-escalation stage to define a recommended dose for the doublet, followed by dose-expansion cohorts to look for preliminary antitumor activity using investigator-assessed objective response rate in adults with advanced/metastatic, relapsed/refractory, unresectable solid tumors. The scientific angle is platform-style combination development for a new cytotoxic mechanism paired with established cytotoxics, aiming to find tolerable schedules/doses that can be carried into tumor-specific expansions. In this broad advanced solid-tumor setting, today’s care is histology- and biomarker-driven systemic therapy (targeted therapy and immunotherapy when eligible, otherwise sequential chemotherapies), and this study explores whether adding a novel transcription inhibitor can deepen responses beyond standard chemo backbones.