30 SEP 2026 — A first-of-its-kind drug that attacks a weak point in some cancers has passed its first human trial with a manageable safety record. Tumours shrank in 7 of 66 patients and stopped growing for a time in most of the rest, according to results published in Nature Medicine on 29 September.
Almost all the patients had already been treated with immunotherapy, which is the standard treatment for these cancers. The trial is now enrolling in several countries, including Malaysia, South Korea and China.
The target
The drug targets cancers with microsatellite instability, or MSI. These tumours have lost one of the cell's systems for fixing DNA copying errors, so short repeated stretches of their DNA grow and shrink as the cells divide. MSI appears in 4% to 7% of advanced bowel cancers and 15% to 25% of advanced womb cancers, the paper says.
Those cancers come to depend on an enzyme called Werner syndrome helicase, or WRN, which unwinds tangled DNA structures that form in the damaged repeats. In laboratory models, cells without MSI manage without it. Blocking WRN should therefore kill MSI cancer cells and spare others, an approach called synthetic lethality.
What the trial found
The drug, RO7589831, also known as VVD-133214, binds permanently to WRN. The trial gave it to 88 people with advanced MSI or related tumours at doses from 150 mg once a day up to 1,000 mg twice a day, with some three-times-daily schedules. Most patients had bowel cancer. They had received a median of three earlier treatments, and 95.5% had already had immunotherapy.
Among the 66 patients whose tumours could be assessed, 74.2% had their disease controlled, meaning it shrank or stayed stable. Seven had confirmed partial responses, where tumours shrink by at least 30%: three with bowel cancer, three with womb cancer and one with ovarian cancer. Median progression-free survival was 6.7 months.
Side effects
The most common side effects were nausea (54.5%), diarrhoea (43.2%), fatigue (39.8%), anaemia (37.5%) and vomiting (30.7%), mostly mild or moderate. Severe anaemia affected 11.4% of patients. Three of the 88 stopped the drug because of side effects, and no side effect was fatal.
The trial did not find a maximum tolerated dose. The team picked two doses, 150 mg and 600 mg twice a day, to compare in the next stage.
The caveats
Response rates of about one in ten are modest, and a phase 1 trial is designed to test safety, not to prove benefit. There was no comparison group.
The researchers could not directly confirm that the drug was hitting WRN inside tumours. Only 5 of 26 paired biopsies had enough tumour cells to analyse, which the authors put down to the mucus-rich tissue common in these cancers. Signs from tumour DNA in the blood and from PET scans supported biological activity, they write.
A second WRN drug, HRO761, which binds reversibly, has reported similar results in its own early trial, with response rates of 8.6% overall. The paper describes those results as consistent with its own.
What comes next
The drug was discovered by Vividion Therapeutics. Roche sponsored the trial at first, and Vividion now does, according to the paper. Part 2 is testing the drug with bevacizumab, an existing drug that restricts tumour blood supply, in bowel cancer, and a combination with the immunotherapy pembrolizumab in untreated patients is planned.
The trial registry lists 280 planned participants and sites in 11 countries, including Malaysia. In an accompanying commentary, Jia Liu of the Kinghorn Cancer Centre in Sydney describes WRN inhibition as a way to target these tumours beyond immunotherapy.
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