pevonedistat + pembrolizumab

This combination therapy consists of pevonedistat, a small molecule inhibitor of the NEDD8-activating enzyme (NAE), and pembrolizumab, a humanized monoclonal antibody targeting the programmed cell death protein 1 (PD-1) receptor. Pevonedistat blocks the neddylation of cullin-RING ligases, which leads to the accumulation of tumor-suppressive proteins and the induction of apoptosis in cancer cells. Pembrolizumab acts as an immune checkpoint inhibitor, preventing the interaction between PD-1 and its ligands (PD-L1 and PD-L2), thereby enhancing the T-cell mediated immune response against the tumor. This specific regimen is being investigated by the M.D. Anderson Cancer Center for the treatment of metastatic or locally advanced unresectable solid tumors characterized by mismatch repair deficiency (dMMR) or high-frequency microsatellite instability (MSI-H), particularly in patients who have previously progressed on anti-PD-1/L1 therapies.

Other names

Pevonedistat and Pembrolizumab in dMMR/MSI-H Cancers