GSK4524101 + niraparib

GSK4524101 + niraparib is an oral combination of two small molecule inhibitors intended for the treatment of advanced or metastatic solid tumors. GSK4524101 is an investigational inhibitor targeting DNA polymerase theta (POLQ), which mediates the microhomology-mediated end-joining (MMEJ) DNA repair pathway; it is generally not detectable in normal tissues but is upregulated in various tumor types. Niraparib is an approved poly(ADP-ribose) polymerase (PARP) inhibitor that impairs repair of double-strand DNA breaks, particularly effective in tumors with homologous recombination deficiency (HRd). The rationale for this combination is to induce synthetic lethality by inhibiting complementary DNA repair pathways in tumor cells, which may enhance anti-tumor efficacy compared to PARP inhibitor alone. The combination is being studied in an open-label, phase 1/2 clinical trial to determine its safety, pharmacokinetics, and preliminary anti-tumor activity in solid tumors[1][3][5].

Brand names

Zejula

Other names

POLQ inhibitor + PARP inhibitorGSK4524101 plus niraparibGSK-4524101 plus niraparibGSK 4524101 plus niraparib