Phase I Study Of Margetuximab (Mgah22), An Fc-Modified Chimeric Monoclonal Antibody (Mab), In Patients (Pts) With Advanced Solid Tumors Expressing The Her2 Oncoprotein.

3004 Background: The anti-HER2 MAb, trastuzumab (H), has proven effective for HER2+ breast cancer (BC) and gastroesophageal cancer (GEC). H’s mechanism of action is incompletely understood, but evidence indicates ADCC is important. MGAH22 is an Fc-modified chimeric MAb which preserves the antigen binding properties of H, and exhibits enhanced binding to the activating low affinity Fcg receptor, CD16A, and diminished binding to the inhibitory low affinity Fcg receptor, CD32B. Preclinical data indicate MGAH22 is more potent than H. Methods: 34 pts with HER2 positive (2+ or 3+ by IHC) tumors have been treated: 19 in 5 dose-escalation cohorts (0.1 - 6.0 mg/kg qw x 4); 15 in 6.0 mg/kg expansion. Tumor types include: BC (10), GEC (13), colon (5), lung (2), salivary (1), ampulla of Vater (1), endometrium (1), bladder (1). Results: MGAH22 was well tolerated. Most common adverse events (AEs) were Grade 1-2 constitutional symptoms and infusion-related reactions. Related AEs ≥ Grade 3 were limited to a single infusi...