Vividion Therapeutics starts Phase II of WRN inhibitor VVD-214 in first-line MSI‑high/dMMR colorectal cancer

Trial initiation and design

Vividion has dosed the first patient in a global Phase II randomized study (NCT07811193) evaluating oral WRN inhibitor VVD-214 combined with pembrolizumab versus pembrolizumab alone as first-line therapy for advanced microsatellite instability-high (MSI-high) or deficient mismatch repair (dMMR) colorectal cancer. The trial is planned to enroll approximately 140 patients across about 21 countries in North America, Latin America, Europe and Asia. The primary endpoint is the six-month progression-free survival rate, with secondary endpoints including objective response rate, disease control rate, duration of response, overall survival and safety.

Mechanism and prior clinical evidence

VVD-214 is an oral small-molecule inhibitor of Werner helicase (WRN), a DNA repair enzyme and a synthetic-lethal target for MSI-high or dMMR cancers; by inhibiting WRN it is designed to selectively induce lethal DNA damage in cancer cells. Preliminary data from a Phase Ia study, presented at AACR 2025 and published in Nature Medicine, reported that VVD-214 was well tolerated with early signals of activity.

Program expansion and concurrent studies

The Phase II expands the program into the first-line setting following encouraging early clinical evidence and investigator interest. Vividion is also running a Phase Ib trial (NCT06004245) testing VVD-214 with bevacizumab in patients whose disease progressed after prior therapy, and continues other early clinical programs including Phase I studies of an oral KEAP1 activator and a RAS-PI3Kα inhibitor.