Purpose: Necitumumab is a second-generation, recombinant, human immunoglobulin G1 monoclonal antibody that blocks the ligand binding site of the epidermal growth factor receptor. The primary objective of this phase 2 study, conducted in accordance with International Conference on Harmonisation E14 guidance, was to determine the effect of necitumumab treatment on QT/QTc interval in patients with advanced solid tumors.
Methods: Patients received necitumumab monotherapy at an absolute dose of 800 mg, once per week for each 6-week cycle. Triplicate electrocardiogram readings were taken at pretreatment (baseline) and then weekly at multiple timepoints that were time-matched with blood samples to determine necitumumab concentrations.
Results: Seventy-five patients received treatment. Overall, the upper bound of the two-sided 90 % confidence interval for mean change from baseline in QTc in cycle 1 did not exceed 10 ms. No patients had a mean QTcF interval >500 ms, and no patients had an increase of >60 ms. Necitumumab concentration-QTc analysis also showed that necitumumab is unlikely to cause QTc prolongation.
Conclusions: The results demonstrate lack of effect of necitumumab on the QTc interval in heavily pretreated patients with advanced solid tumors, suggesting that QT prolongation is not a major safety concern for necitumumab at the recommended therapeutic dose. The safety profile was consistent with the known safety profile of necitumumab.
Keywords: Cancer; Epidermal growth factor receptor inhibitor; Monoclonal antibodies; Necitumumab; QTc interval.