Evaluation of the effect of necitumumab on the corrected QT interval in patients with advanced solid tumors.
OBJECTIVE
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.
University of Michigan, 1500 E Medical Center Drive SPC 5913, Ann Arbor, MI, 48109, USA. dcsmith@med.umich.edu.
David C
DC
Smith
Carolina BioOncology Institute, Huntersville, NC, USA.
John
J
Powderly
University of Pittsburgh, Pittsburgh, PA, USA.
James J
JJ
Lee
Cleveland Clinic Foundation, Cleveland, OH, USA.
Dale R
DR
Shepard
Eli Lilly and Company, Solna, Sweden.
Johan
J
Wallin
Eli Lilly and Company, Indianapolis, IN, USA.
Archana
A
Chaudhary
Eli Lilly and Company, Indianapolis, IN, USA.
Grace Yi
GY
Chao
Eil Lilly-NUS, Singapore, Singapore.
Wee Teck
WT
Ng
Eli Lilly and Company, Windlesham, Surrey, UK.
Malcolm I
MI
Mitchell
Eli Lilly and Company, Bad Homburg, Germany.
Gerrit
G
Grau
Eli Lilly and Company, Bad Homburg, Germany.
Raffael
R
Kurek
Yale University, New Haven, CT, USA.
Patricia
P
LoRusso
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C527969:necitumumab
Cancer; Epidermal growth factor receptor inhibitor; Monoclonal antibodies; Necitumumab; QTc interval