Fig. 1

Design of (a) phase 1b and (b) phase 2a. ^aMTD is the highest dose at which 0/3 patients or 1/6 patients experienced a dose-limiting toxicity. ^bBrain metastases that have required any type of therapy to control symptoms in the 60 days prior to first study treatment. ECOG Eastern Cooperative Oncology Group, HER2 human epidermal growth factor receptor 2, LABC locally advance breast cancer, LD loading dose, MBC metastatic breast cancer, MTD maximum tolerated dose, qw weekly, q3w every three weeks, T-DM1 trastuzumab emtansine