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Cancer Chemother Pharmacol. 2016 Aug;78(2):271-80. doi: 10.1007/s00280-016-3074-y. Epub 2016 Jun 16.

Evaluation of the effect of necitumumab on the corrected QT interval in patients with advanced solid tumors.

Author information

1
University of Michigan, 1500 E Medical Center Drive SPC 5913, Ann Arbor, MI, 48109, USA. dcsmith@med.umich.edu.
2
Carolina BioOncology Institute, Huntersville, NC, USA.
3
University of Pittsburgh, Pittsburgh, PA, USA.
4
Cleveland Clinic Foundation, Cleveland, OH, USA.
5
Eli Lilly and Company, Solna, Sweden.
6
Eli Lilly and Company, Indianapolis, IN, USA.
7
Eil Lilly-NUS, Singapore, Singapore.
8
Eli Lilly and Company, Windlesham, Surrey, UK.
9
Eli Lilly and Company, Bad Homburg, Germany.
10
Yale University, New Haven, CT, USA.

Abstract

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

PMID:
27312733
DOI:
10.1007/s00280-016-3074-y
[Indexed for MEDLINE]

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