First-in-Human WRN Inhibitor RO7589831 Shows Promise in Hard-to-Treat MSI/dMMR Cancers

In this Phase 1 trial, RO7589831—a novel, covalent Werner helicase inhibitor—was administered orally at doses from 150 mg to 2000 mg in 44 patients with MSI/dMMR advanced solid tumors, including colorectal, ovarian, and endometrial cancers, most of whom were heavily pretreated with immunotherapy; the agent demonstrated rapid absorption, a favorable safety profile with no dose-limiting toxicities, and promising anti-tumor activity as evidenced by a 68.8% disease control rate, RECIST partial responses, robust FDG-PET metabolic responses, and consistent ctDNA molecular responses.

These results provide early clinical proof-of-concept that targeting WRN in MSI/dMMR tumors can offer a new, effective treatment approach for patients who have progressed on current immunotherapy regimens.