pembrolizumab + VVD-214

pembrolizumab + VVD-214 is an investigational combination therapy consisting of pembrolizumab (Keytruda), a humanized monoclonal antibody targeting the programmed cell death protein 1 (PD-1) receptor, and VVD-214 (RO7589831), an oral, covalent, irreversible, allosteric small-molecule inhibitor of Werner syndrome helicase (WRN). Developed by Vividion Therapeutics (a subsidiary of Bayer), VVD-214 exploits synthetic lethality in tumors characterized by high microsatellite instability (MSI-high) or deficient mismatch repair (dMMR). In these tumors, the loss of mismatch repair pathways makes cancer cells highly dependent on WRN helicase for DNA repair and genomic stability. Inhibiting WRN leads to double-stranded DNA breaks and selective cell death. Pembrolizumab, an immune checkpoint inhibitor, works complementarily by blocking the PD-1/PD-L1 pathway to restore T-cell-mediated antitumor immune responses. The combination is being evaluated in clinical trials, including a Phase 2 study as a first-line treatment for patients with advanced MSI-high or dMMR colorectal cancer, to overcome resistance to immunotherapy and improve clinical outcomes.

Other names

Keytruda + RO7589831Keytruda + VVD-133214Keytruda + VVD-214MK-3475 + RO7589831MK-3475 + VVD-133214MK-3475 + VVD-214RO7589831 + KeytrudaRO7589831 + MK-3475RO7589831 + pembrolizumabVVD-133214 + KeytrudaVVD-133214 + MK-3475VVD-133214 + pembrolizumabVVD-214 + KeytrudaVVD-214 + MK-3475VVD-214 + pembrolizumabpembrolizumab + RO7589831pembrolizumab + VVD-133214pembrolizumab + VVD-214