Anti-EGFR/Anti-HER3 Bispecific Antibody-drug Conjugate AVZO-1418

**Semantic type:** Pharmacologic Substance

**Definition:** An antibody-drug conjugate (ADC) composed of a bispecific antibody, with a fragment antigen binding (Fab) arm targeting the tumor associated antigen (TAA) human epidermal growth factor receptor (EGFR; HER1; ErbB1) with medium affinity connected via a knock-into-hole (KIH) Fc domain to a single chain variable fragment (scFv) arm targeting the TAA human epidermal growth factor receptor 3 (HER3; ErbB3) with high affinity conjugated, via a cleavable tetrapeptide-based linker, to the topoisomerase-1 inhibitor (TOP1i) P1021, with potential antineoplastic activity. Upon administration, anti-EGFR/anti-HER3 bispecific ADC AVZO-1418 simultaneously targets and binds to EGFR and HER3 expressed on cancer cells. Upon binding, internalization and linker cleavage, P1021 is released, and inhibits DNA topoisomerase-1 activity, thereby inhibiting DNA replication and resulting in cell cycle arrest and tumor cell apoptosis. This inhibits the proliferation of tumor cells expressing EGFR and/or HER3. EGFR and HER3, both upregulated and/or mutated in a variety of tumor cell types, play key roles in tumor cell proliferation. HER3 is a dimerization partner of EGFR, and HER3 overexpression is associated with resistance to EGFR inhibition.

**Synonyms:** - AVZO 1418 - AVZO-1418 - AVZO1418 - Anti-EGFR/Anti-HER3 Bispecific ADC AVZO-1418 - Anti-EGFR/Anti-HER3 Bispecific ADC DB-1418 - Anti-EGFR/Anti-HER3/P1021 ADC AVZO-1418 - Anti-EGFR/Anti-HER3/TOP1i ADC AVZO-1418 - Anti-EGFR/HER3 Bispecific ADC AVZO-1418 - DB 1418 - DB-1418 - DB1418 - EGFR x HER3 Bispecific ADC AVZO-1418