ABSTRACT: CT016
CHICAGO, APRIL 27, 2025 ― For patients with cancers harboring certain genetic defects, the first-in-class targeted therapy RO7589831, which targets the DNA repair enzyme Werner helicase, demonstrated early signals of efficacy and was generally well-tolerated, according to Phase I trial data reported by researchers at The University of Texas MD Anderson Cancer Center .
The results were presented today in the clinical trials plenary session at the American Association for Cancer Research (AACR) Annual Meeting 2025 by principal investigator Timothy Yap, M.B.B.S., Ph.D., professor of Investigational Cancer Therapeutics and vice president and head of clinical development in MD Anderson’s Therapeutics Discovery division
“RO7589831 appears generally safe and shows promising signals of anti-tumor efficacy,” Yap said. “These are encouraging early clinical data, especially because this is a patient population that currently has very limited treatment options. This also further validates Werner helicase as an actionable target, which is exciting because many cancers are highly dependent on it for survival.”
Though this targeted therapy is the first in a new class of drugs, it is part of a wider group of therapies targeting the DNA damage response for patients with solid tumors and genetic changes known as high microsatellite instability (MSI) or deficient mismatch repair (dMMR). These can occur in many cancer types, and 40-70% of patients with these types of solid tumors either do not respond to immune checkpoint inhibitors or develop resistance during treatment.
Like other DNA damage response therapies, RO7589831 inhibits the function of a DNA repair enzyme, in this case Werner helicase, to create a buildup of DNA damage within tumor cells, ultimately leading to cell death. Because normal cells do not have MSI, these treatments spare normal cells.
Initial efficacy was evaluated in 37 patients. Five of these patients, representing multiple cancer types with high MSI or dMMR, had partial responses as determined by radiological imaging, and 65.7% of all patients had lasting stable disease. Specialized metabolic imaging showed that deeper metabolic responses were associated with both radiological partial responses and longer-term disease control.
Safety was evaluated in 44 patients, with the majority experiencing grade 1-2 adverse events, though higher doses appeared less tolerable than lower doses. Mild manageable nausea, vomiting and diarrhea were the most common adverse events, and no dose-limiting toxicities were observed.
Three randomized dose-level cohorts are underway to establish the optimal recommended dose for a future Phase II trial.
This trial was funded by Roche. A full list of authors and their disclosures can be found in the abstract here.
Read this press release in the MD Anderson Newsroom. More information on all MD Anderson AACR Annual Meeting content can be found at MDAnderson.org/AACR .
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