amivantamab and recombinant human hyaluronidase

A co-formulation composed of amivantamab, a human bispecific antibody targeting both epidermal growth factor receptor EGFR and hepatocyte growth factor receptor (HGFR; c-Met), and a recombinant form of human hyaluronidase, with potential antineoplastic activity. Upon subcutaneous administration of amivantamab and recombinant human hyaluronidase, the hyaluronidase reversibly depolymerizes the polysaccharide hyaluronan in the subcutaneous tissue. This increases the permeability of the subcutaneous tissue and enhances the absorption of amivantamab into the systemic circulation. In turn, amivantamab simultaneously targets and binds to wild-type or certain mutant forms of both EGFR and c-Met expressed on cancer cells, thereby preventing receptor phosphorylation. This prevents the activation of both EGFR- and c-Met-mediated signaling pathways. In addition, binding results in receptor degradation, which further inhibits EGFR- and c-Met-mediated signaling. Amivantamab also causes antibody-dependent cellular cytotoxicity (ADCC). Altogether, this results in the inhibition of tumor cell proliferation. When administered subcutaneously, hyaluronidase, an endoglycosidase, increases the dispersion and absorption of co-administered drugs. EGFR and c-Met, upregulated or mutated in a variety of tumor cell types, play key roles in tumor cell proliferation.