PURPOSE: This study aimed to determine a maximum tolerated dose (MTD) and 
recommended dose for disease-directed studies of necitumumab (IMC-11F8), a fully 
human IgG(1) monoclonal antibody directed at the epidermal growth factor 
receptor, and to characterize the safety profile, pharmacokinetics, preliminary 
antitumor activity, and immunogenicity of necitumumab.
EXPERIMENTAL DESIGN: Patients with advanced solid malignancies were treated with 
100 to 1,000 mg (flat dosing) necitumumab followed by a 2-week pharmacokinetics 
sampling period, before beginning 6-week cycles of therapy.
RESULTS: Sixty patients received necitumumab weekly (29 patients) or every other 
week (31 patients). Two patients receiving 1,000 mg every 2 weeks experienced 
dose-limiting toxicities (DLT; grade 3 headache), accompanied by grade 3 nausea 
and vomiting in one patient. Occurring hours after the initial dose, these DLTs 
established 800 mg as the MTD. Mild dose-related skin toxicity was the most 
common drug-related toxicity (80%). One patient in each arm experienced grade 3 
acneform rash, which responded to oral antibiotics and topical therapy. Toxicity 
was similar on both schedules. Necitumumab exhibited saturable elimination and 
nonlinear pharmacokinetics. At 800 mg (both arms), its half-life was 
approximately 7 days. All patients treated with >or=600 mg necitumumab achieved 
target trough concentrations (>or=40 microg/mL). Antibodies against necitumumab 
were not detected. Partial response and stable disease were experienced by 2 and 
16 patients, respectively.
CONCLUSION: Well tolerated, necitumumab is associated with preliminary evidence 
of antitumor activity, and achieves biologically relevant concentrations 
throughout the dosing period. The recommended dose of necitumumab for further 
clinical development is 800 mg (flat dose) weekly or every 2 weeks based on the 
clinical setting.