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This combination therapy consists of the Wee1 kinase inhibitor adavosertib (AZD1775) and the FLAG chemotherapy regimen, which includes fludarabine, cytarabine, and filgrastim. Adavosertib works by inhibiting the WEE1 G2 checkpoint kinase, a key regulator of the G2/M cell cycle checkpoint. By inhibiting WEE1, the drug prevents cancer cells from repairing DNA damage before entering mitosis, thereby sensitizing them to DNA-damaging agents. Fludarabine and cytarabine are antimetabolites that interfere with DNA synthesis and repair, while filgrastim (G-CSF) is a hematopoietic growth factor used to stimulate white blood cell production and potentially prime leukemia cells for chemotherapy. This combination is primarily being investigated for the treatment of relapsed or refractory acute myeloid leukemia (AML), particularly in pediatric and young adult populations.
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