WRN inhibitor records seven partial responses in an early cancer trial
Initial clinical results are out for the experimental WRN inhibitor RO7589831 in patients with advanced cancers carrying particular DNA repair defects. Seven of 66 evaluable patients had confirmed partial tumor responses in a phase 1 trial. The study primarily investigated safety and suitable dosing. The responses support further testing in this patient group, but they do not establish an approved treatment or a definitive clinical benefit.
Science··Midday
Early trial, defined group
The first human study of RO7589831 tested a drug that blocks the Werner helicase, or WRN, an enzyme involved in unwinding DNA. The treatment was investigated in advanced solid tumors with microsatellite instability or deficient mismatch repair. MD Anderson and the published trial describe the same phase 1 program: 88 people entered the dose-escalation part, while 66 patients with microsatellite instability could be assessed for an antitumor response. The patients formed a selected molecular subgroup rather than all people with cancer.[1], [2]
Responses and adverse events
Seven of those 66 patients had a confirmed partial tumor response, a response rate of 10.6 percent under the study criteria. The investigators also classified 49 as having disease control, a broader measure that includes stable disease. Nausea, diarrhea, fatigue, anemia and vomiting were among the common treatment-emergent events. One dose-limiting case of moderate nausea appeared at the highest three-times-daily schedule. Three participants stopped treatment after adverse events; the protocol-defined maximum tolerated dose was not reached.[1]
What this stage establishes
The trial chiefly sought a dose and schedule suitable for further study, while tumor response and survival measures were secondary outcomes. It had no control group and included different cancer types and treatment histories, so the observed outcomes cannot be assigned to the drug with the confidence a comparative trial would provide. The authors also could not demonstrate direct target engagement in tumor tissue. The partial responses are a reason to investigate WRN inhibition further in this defined group, not a measure of benefit for patients outside it.[1]
