Emerging evidence demonstrates that a c-Met antibody-drug conjugate (ADC) has superior efficacy and safety profiles compared with those of currently available small molecules or antibody inhibitors for the treatment of c-Met-overexpressing cancers.Here we described both the in vitro and in vivo efficacies of SHR-A1403,a novel c-Met ADC composed of a humanized IgG2 monoclonal antibody against c-Met conjugated to a novel cytotoxic microtubule inhibitor.SHR-A1403 showed high affinity to c-Met proteins derived from human or monkey and potent inhibitory effects in cancer cell lines with high c-Met protein expression.In mice bearing tumors derived from cancer cell lines or patient HCC tissues with confirmed c-Met overexpression,SHR-A1403 showed excellent anti-tumor efficacy.Antibody binding with c-Met contributed to SHR-A1403 endocytosis;the subsequent translocation to lysosomes and cytotoxicity of the released toxin are speculated to be predominant mechanisms underlying the anti-tumor activity of SHR-A1403.In conclusion,SHR-A1403 showed significant anti-tumor activity in cancer cell lines,xenograft mouse models and an HCC PDX model,which all have high c-Met levels.These data provide references for SHR-A1403 as a potential therapy for the treatment of cancers with c-Met overexpression.