Updated findings of a first-in-human, phase I study of margetuximab (M), an Fc-optimized chimeric monoclonal antibody (MAb), in patients (pts) with HER2-positive advanced solid tumors.

523 Background: Fc-dependent mechanisms such as antibody-dependent cellular cytotoxicity (ADCC) may be important for the activity of MAbs. M is a MAb to HER2 engineered for increased Fc-domain binding affinity to both low affinity variants of the activating Fcγ receptor, CD16A. In preclinical studies, M showed enhanced ADCC compared to an unmodified precursor. Results from the initial dose escalation have previously been reported. Here we describe pharmacokinetics (PK), safety and activity data for the expansion cohort and an alternative schedule, including responses in patients with refractory breast cancer (BC). Methods: Pts with refractory carcinomas that overexpress HER2 for whom no standard therapy was available were enrolled. Pt cohorts received escalating doses of M weekly for 3 of every 4 weeks (Regimen A) or every 3 weeks (Regimen B) by intravenous infusion in a 3+3 (Regimen A) or 6+6 (Regimen B) design. Additional safety and activity data were obtained in expansion cohorts of each regimen. Tumor...