Patients in the study will receive either pembrolizumab alone or the same treatment alongside an experimental oral drug. Vividion dosed the first participant on October 15, 2026, in a randomized, open-label Phase 2 trial for previously untreated advanced MSI-high or dMMR colorectal cancer, as Vividion and Bayer announced.
The global trial, NCT07811193, plans to enroll approximately 140 adults at clinical sites in about 21 countries. Those sites will span North America and Latin America, as well as Europe and Asia. Participants must have histologically or cytologically confirmed unresectable or metastatic colorectal adenocarcinoma and confirmed MSI-high and/or dMMR tumor status.
The primary endpoint is the proportion of patients alive without disease progression at six months. Secondary measures include objective response and disease control. The trial will also assess duration of response, overall survival and safety.
Testing a DNA-repair target
VVD-214 is an investigational oral small-molecule inhibitor of Werner helicase, or WRN, a DNA-repair enzyme. Vividion describes WRN as a synthetic lethal target in MSI-high or dMMR cancers. Its proposed mechanism rests on the dependence of these tumor cells on WRN to maintain DNA stability. The drug is designed to trigger lethal DNA damage selectively in cancer cells while minimizing harm to normal cells. Whether it achieves that selectivity or provides a therapeutic benefit remains to be established. According to the company, approximately 15 percent of colorectal tumors are MSI-high.
The evidence is still early. Preliminary Phase 1a data presented at the American Association for Cancer Research 2025 Annual Meeting and published in Nature Medicine showed that the drug was well tolerated and had early signs of activity. The Phase 2 trial will test whether adding VVD-214 to pembrolizumab improves outcomes over pembrolizumab alone.
Vividion is also testing VVD-214 with bevacizumab in a Phase 1b trial for patients whose MSI-high or dMMR colorectal cancer progressed after prior treatment. That study covers previously treated patients, while the new trial moves the drug into first-line treatment. As with the first-patient milestone in a separate CAR-NK trial, this marks clinical development activity. It does not establish that the treatment works.
Moving into earlier treatment
Vividion CEO Aleksandra Rizo said early clinical data and investigator interest had strengthened the company’s conviction in WRN inhibition. She said they supported moving into first-line disease. Bayer Pharmaceuticals research and development head Christian Rommel said the company aims to assess VVD-214 as a potential treatment option for this patient group.
Pembrolizumab is an established first-line treatment for unresectable or metastatic MSI-high or dMMR colorectal cancer. In the KEYNOTE-177 trial, median progression-free survival was 16.5 months with pembrolizumab, compared with 8.2 months with chemotherapy. The hazard ratio for progression or death was 0.60.
Vividion is a wholly owned and independently operated subsidiary of Bayer. The FDA approved pembrolizumab for this first-line indication on June 29, 2020.
