Reynolds KL, et al. - In this phase I study of anti-human epidermal growth factor receptor 3 (HER3) monoclonal antibody LJM716, analysts sought to delineate the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE), and dosing schedule, and to characterize safety/tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity. This study found LJM716 as well tolerated. In addition, MTD was not reached, and the RDE was 40 mg/kg QW.

Methods

• Dose escalation, followed by expansion in patients with squamous cell carcinoma of the head and neck or esophagus, and HER2-overexpressing metastatic breast cancer or gastric cancer were incorporated in this study.
• Patients received LJM716 intravenous once weekly (QW) or every two weeks (Q2W), in 28-day cycles, during dose escalation.
• They employed an adaptive Bayesian logistic regression model to guide dose escalation and establish the RDE.
• Modulation of HER3 signaling was assessed by exploratory pharmacodynamic tumor studies.

Results

• LJM716 3–40 mg/kg QW and 20 mg/kg Q2W were administered to patients (54 patients; 36 patients at 40 mg/kg QW).
• This study did not report dose-limiting toxicities (DLTs) during dose-escalation.
• In the expansion phase, one patient experienced two DLTs (diarrhea, hypokalemia [both grade 3]).
• Providing drug levels above the preclinical minimum effective concentration, the RDE was 40 mg/kg QW.
• They revealed an unconfirmed partial response in one patient with gastric cancer.
• Moreover, 17/54 patients had stable disease, two lasting >30 weeks.
• They noticed down-modulation of phospho-HER3 in paired tumor samples.