Here we report a phase I study that evaluated the safety, activity, and biomarkers of LZM005, a HER2 antibody, used as a monotherapy or in combination with trastuzumab plus docetaxel in patients with HER2-positive MBC....With regard to the PFS impact of genomic alterations, we found that KMT2B, MUC16, and KIR3DL2 were associated with PFS in the univariate Cox model.patients with KMT2B mutations had a longer progression-free interval (NR vs. 5.67 months, HR 0.2, p = 0.045) than their non-alters while patients with MUC16 (5.63 months vs. 11.10 months, HR 3.84, p = 0.035) or KIR3DL2 (5.67 months vs. 13.17 months, HR 4.0, p = 0.033) mutations showed faster progression than their counterparts.