pertuzumab, trastuzumab, and hyaluronidase-zzxf

A ready-to-use fixed-dose combination of pertuzumab and trastuzumab, both recombinant humanized monoclonal antibodies directed against the tyrosine kinase receptor (TKR) human epidermal growth factor receptor 2 (HER2; HER-2; receptor tyrosine-protein kinase erbB-2), and hyaluronidase-zzxf, a biosimilar of the recombinant form of the naturally occurring endoglycosidase hyaluronidase, with antineoplastic activity that can be used for the treatment of HER2-overexpressing breast cancers. Upon subcutaneous administration, hyaluronidase-zzxf temporarily breaks down the hyaluronan barrier, which decreases viscosity of, and allows both pertuzumab and trastuzumab to spread rapidly through the interstitial space. This improves access to lymphatic and capillary vessels and facilitates the absorption of both antibodies into the bloodstream. Pertuzumab targets and binds to the extracellular dimerization domain (subdomain II) of HER2 and blocks ligand-dependent heterodimerization of HER2 with other HER family members, including EGFR, HER3 and HER4. This inhibits ligand-initiated intracellular signaling and prevents the activation of the mitogen-activated protein (MAP) kinase and the phosphoinositide 3-kinase (PI3K) signaling pathways, leading to growth arrest and apoptosis in HER2-overexpressing tumor cells, respectively. Trastuzumab targets and binds to subdomain IV of HER2 and inhibits ligand-independent, HER2 mediated cell proliferation and inhibits the PI3K signaling pathway in HER2-overexpressing tumor cells. Both antibodies induce an antibody-dependent cell-mediated cytotoxicity (ADCC) against HER2-expressing tumor cells. HER2 is overexpressed in many adenocarcinomas, particularly breast adenocarcinomas.