A phase 1 dose-escalation study of anti-HER3 monoclonal antibody LJM716 in combination with trastuzumab in patients with HER2-overexpressing metastatic breast or gastric cancer.

2519 Background: TheHER2-HER3 heterodimer, a key driver in HER2-positive tumors, is not completely blocked by available therapies. LJM716 is a fully human anti-HER3 monoclonal antibody (mAb) shown to enhance trastuzumab activity in HER2+ preclinical breast and gastric cancer models. Methods: This phase 1, open-label study is currently evaluating LJM716 in combination with trastuzumab in patients (pts) with HER2+ metastatic breast (MBC) or gastric (MGC) cancer who failed previous HER2-directed therapy. The objective for the dose-escalation part of the study was to estimate the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE). Results: As of October 4, 2013, 35 pts (escalation, n = 17; expansion, n = 18) were enrolled (MBC, n = 29; MGC, n = 6) and treated intravenously with LJM716 at dose levels (DLs) 3, 10, 20, or 40 mg/kg once weekly (QW) in combination with trastuzumab 2 mg/kg QW. All pts had prior antineoplastic therapy, including 19 (54%) with ≥ 3 regimens. Common treatment-rela...