niraparib + anti-PD1 antibody

Niraparib + anti-PD1 antibody is a combination therapy consisting of the oral small molecule poly(ADP-ribose) polymerase (PARP) inhibitor niraparib and an immune checkpoint inhibitor targeting programmed cell death protein 1 (PD-1), such as pembrolizumab or dostarlimab. Niraparib inhibits PARP-1 and PARP-2 enzymes involved in DNA repair via the homologous recombination pathway. By blocking these enzymes, it induces synthetic lethality in tumor cells with deficient DNA repair mechanisms and also modulates the tumor immune microenvironment by increasing cytosolic DNA fragments that activate the cGAS-STING pathway to stimulate type I interferon production. Anti-PD1 antibodies are monoclonal antibodies that block PD-1 on T cells to prevent its interaction with PD-L1/PD-L2 on tumor cells, thereby enhancing T cell-mediated antitumor immunity. The rationale for combining these agents is based on preclinical evidence showing synergistic effects through increased neoantigen production, enhanced antigen presentation, upregulation of PD-L1 expression via STING activation or GSK3β inactivation, and improved recruitment and activity of cytotoxic lymphocytes within tumors[1][2][4]. This combination has been investigated primarily for advanced solid tumors including ovarian cancer[3], triple-negative breast cancer[4], endometrial cancer[6], non-small cell lung cancer[5], and others.

Other names

niraparib plus pembrolizumabniraparib plus dostarlimabPARP inhibitor plus PD-1 inhibitor