Lurbinectedin + olaparib

Lurbinectedin + olaparib is an investigational combination therapy being studied primarily in advanced solid tumors such as high-grade ovarian cancer, endometrial cancer, and triple-negative breast cancer. Lurbinectedin is a synthetic alkaloid structurally related to trabectedin that binds to the minor groove of DNA at GC-rich sequences, forming DNA adducts that induce double-strand breaks and disrupt transcription processes in tumor cells. Olaparib is a small molecule inhibitor of poly(ADP-ribose) polymerase (PARP), an enzyme involved in DNA repair; by inhibiting PARP, it prevents the repair of single-strand breaks leading to cell death especially in tumors with homologous recombination deficiency (e.g., BRCA mutations). The rationale for combining these agents is to maximize DNA damage and enhance antitumor efficacy by simultaneously inducing DNA lesions (lurbinectedin) and blocking their repair (olaparib). This combination has shown feasibility and tolerability in early-phase clinical trials with disease control rates above 60%[4][5][6].

Brand names

Zepzelca + Lynparza

Other names

lurbinectedin and olaparib