Safety of panitumumab-IRDye800CW and cetuximab-IRDye800CW for fluorescence-guided surgical navigation in head and neck cancers

Abstract

Purpose: To demonstrate the safety and feasibility of leveraging therapeutic antibodies for surgical imaging.Procedures: We conducted two phase I trials for anti-epidermal growth factor receptor antibodies cetuximab-IRDye800CW (n=12) and panitumumab-IRDye800CW (n=15).Adults with biopsy-confirmed head and neck squamous cell carcinoma scheduled for standard-of-care surgery were eligible.For cetuximab-IRDye800CW, cohort 1 was intravenously infused with 2.5 mg/m 2 , cohort 2 received 25 mg/m 2 , and cohort 3 received 62.5 mg/m 2 .For panitumumab-IRDye800CW, cohorts received 0.06 mg/kg, 0.5 mg/kg, and 1 mg/kg, respectively.Electrocardiograms and blood samples were obtained, and patients were followed for 30 days post-study drug infusion.Results: Both fluorescently labeled antibodies had similar pharmacodynamic properties and minimal toxicities.Two infusion reactions occurred with cetuximab and none with panitumumab.There were no grade 2 or higher toxicities attributable to cetuximab-IRDye800CW or panitumumab-IRDye800CW; fifteen grade 1 adverse events occurred with cetuximab-I RDye800CW, and one grade 1 occurred with panitumumab-IRDye800CW.There were no significant differences in QTc prolongation between the two trials (p=0.8).Conclusions: Panitumumab-IRDye800CW and cetuximab-IRDye800CW have toxicity and pharmacodynamic profiles that match the parent compound, suggesting that other therapeutic antibodies may be repurposed as imaging agents with limited preclinical toxicology data.