ART6043 + olaparib

ART6043 + olaparib is an investigational oral combination therapy for advanced or metastatic solid tumors with defective DNA repair. **ART6043** is a selective, orally bioavailable, small-molecule inhibitor of the polymerase domain of **DNA polymerase theta (Polθ)**, an enzyme critical for error-prone DNA repair in cancer cells. By inhibiting Polθ, ART6043 impairs the ability of cancer cells to repair DNA damage. **Olaparib** is a small-molecule **PARP inhibitor** that also blocks DNA repair. Combining ART6043 with olaparib is designed to exploit synthetic lethality in cancers with homologous recombination deficiencies (such as BRCA-mutated cancers), potentially increasing anti-tumor efficacy versus either agent alone. The combination is being developed primarily for patients with solid tumors characterized by loss-of-function mutations in DNA damage response (DDR) genes, such as BRCA1/2, and is being evaluated in Phase 1/2 trials for safety and preliminary efficacy[1][3][5][6].