CPI-613 + gemcitabine + nab-paclitaxel

This is a combination regimen consisting of CPI-613 (devimistat), gemcitabine, and nab-paclitaxel (Abraxane) primarily investigated for the treatment of locally advanced or metastatic pancreatic cancer. CPI-613 is a first-in-class small molecule that targets altered energy metabolism in cancer cells by inhibiting key mitochondrial enzymes—pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase (KGDH)—thereby disrupting the tricarboxylic acid (TCA) cycle and suppressing ATP production essential for tumor cell survival[5][6][8]. Gemcitabine is a nucleoside analog that inhibits DNA synthesis, while nab-paclitaxel is an albumin-bound formulation of paclitaxel that stabilizes microtubules to inhibit cell division. The combination aims to enhance antitumor activity through metabolic disruption and cytotoxic effects. Clinical studies have shown this regimen has significant antitumor activity with manageable toxicity in patients with metastatic pancreatic ductal adenocarcinoma[1][4][5].