New Targeted Therapy Shows Promise in Treating Certain Cancers: Phase I Trial Results

Researchers at The University of Texas MD Anderson Cancer Center have reported promising early results from a Phase I clinical trial of a novel targeted therapy, RO7589831. This drug is the first in its class to inhibit the DNA repair enzyme Werner helicase, a protein that many cancer cells depend on for survival.

The study, presented at the AACR Annual Meeting 2025 by lead investigator Dr. Timothy Yap, indicates that RO7589831 is generally well-tolerated and demonstrates signs of anti-tumor activity in patients with cancers harboring specific genetic defects, such as high microsatellite instability (MSI) or deficient mismatch repair (dMMR). These genetic features are common in various solid tumors and often limit the effectiveness of existing treatments.

In the trial, efficacy was observed in 37 patients, with five experiencing partial responses and over 65% maintaining stable disease for a significant duration. Metabolic imaging suggested deeper tumor responses in some cases correlated with better clinical outcomes. Safety assessments involving 44 patients showed mostly mild adverse events, like nausea, vomiting, and diarrhea, mainly at lower doses. Notably, no dose-limiting toxicities were recorded. Different dosing cohorts are continuing to determine the optimal dose for subsequent studies.

The mechanism behind RO7589831 involves blocking Werner helicase, leading to an accumulation of DNA damage in tumor cells, which results in tumor cell death while sparing normal cells that lack MSI or dMMR features. This approach aligns with other DNA damage response therapies targeting tumors with genetic vulnerabilities.

Funding for this research was provided by Roche. The ongoing studies aim to further evaluate this innovative therapy's potential as a treatment option for difficult-to-treat cancers, especially those resistant to current immunotherapies or with limited options.

These findings highlight the potential of targeting DNA repair pathways in personalized cancer therapy, offering hope for more effective treatments for patients with specific genetic tumor profiles.