pembrolizumab + devinostat

Pembrolizumab + devinostat is an investigational combination therapy being evaluated for the treatment of various solid tumors. **Pembrolizumab** (Keytruda) is a well-established humanized monoclonal antibody that acts as a checkpoint inhibitor by targeting the programmed cell death protein 1 (PD-1) receptor, thereby enhancing the immune system's ability to detect and destroy tumor cells. **Devinostat** (CPI-613) is a first-in-class small molecule lipoate analog developed by Cornerstone Pharmaceuticals (now Rafael Pharmaceuticals). It functions as a mitochondrial metabolism inhibitor that selectively targets the altered energy metabolism of cancer cells by inhibiting the alpha-ketoglutarate dehydrogenase (KGDH) and pyruvate dehydrogenase (PDH) enzyme complexes. By disrupting the TCA cycle, devinostat increases oxidative stress and sensitizes tumor cells to other therapies. The combination aims to leverage the metabolic disruption caused by devinostat to enhance the anti-tumor immune response elicited by pembrolizumab, particularly in advanced or metastatic solid tumors that have failed standard treatments.

Brand names

Keytruda

Other names

Pembrolizumab + CPI-613Keytruda + Devinostat