azenosertib + carboplatin

azenosertib + carboplatin is a combination investigational therapy composed of azenosertib, a selective, orally bioavailable WEE1 kinase inhibitor, and carboplatin, a platinum-based chemotherapy. Azenosertib functions by inhibiting WEE1, a kinase involved in the regulation of the G2/M cell cycle checkpoint, which impairs DNA damage repair and sensitizes tumor cells to DNA-damaging agents like carboplatin. Carboplatin induces DNA crosslinking that leads to cell death, especially in rapidly dividing tumor cells. This combination aims to enhance efficacy against cancers that are refractory or resistant to platinum-based chemotherapy by exploiting synthetic lethality, particularly in tumors with Cyclin E1 amplification or other defects in cell cycle regulation. Clinical studies are evaluating this regimen primarily in platinum-resistant/refractory ovarian cancer and in combination with other agents in metastatic triple-negative breast cancer. Early-phase trials show promising clinical activity and tolerability, with objective response rates in ovarian cancer and ongoing studies for dose finding and efficacy in breast cancer[1][2][6][8].