VX-984 + pegylated liposomal doxorubicin

VX-984 + pegylated liposomal doxorubicin (PLD) is an investigational combination therapy being studied for advanced solid tumors and recurrent or metastatic endometrial cancer. VX-984 (also known as M9831) is a potent, selective small molecule inhibitor of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), a key enzyme involved in the non-homologous end joining (NHEJ) pathway for repairing double-strand breaks in DNA. By inhibiting DNA-PKcs activity, VX-984 impairs NHEJ-mediated repair and increases sensitivity to agents that induce double-strand breaks such as radiation or certain chemotherapies[1][4][6]. Pegylated liposomal doxorubicin (PLD), marketed under brand names such as Doxil and Caelyx, is a formulation of the anthracycline chemotherapy drug doxorubicin encapsulated in PEG-coated liposomes to improve pharmacokinetics and reduce toxicity. The combination aims to enhance antitumor efficacy by combining direct cytotoxicity from PLD with impaired tumor cell repair capacity due to DNA-PK inhibition by VX-984[5][8]. Clinical studies have evaluated this combination primarily in patients with advanced solid tumors who have progressed through standard therapies or for whom PLD may be considered standard of care[5][8].

Other names

DNA-dependent protein kinase inhibitor VX-984DNA-PK inhibitor VX-984pegylated liposomal doxorubicin