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- Title
Evaluation of the effect of necitumumab on the corrected QT interval in patients with advanced solid tumors.
- Authors
Smith, David; Powderly, John; Lee, James; Shepard, Dale; Wallin, Johan; Chaudhary, Archana; Chao, Grace; Ng, Wee; Mitchell, Malcolm; Grau, Gerrit; Kurek, Raffael; LoRusso, Patricia; Smith, David C; Lee, James J; Shepard, Dale R; Chao, Grace Yi; Ng, Wee Teck; Mitchell, Malcolm I
- Abstract
<bold>Purpose: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
ELECTROCARDIOGRAPHY; IMMUNOGLOBULIN G; MONOCLONAL antibodies; MOLECULAR cloning; ELECTRODIAGNOSIS; ANTINEOPLASTIC agents; CLINICAL trials; COMPARATIVE studies; RESEARCH methodology; MEDICAL cooperation; RESEARCH; TUMORS; LONG QT syndrome; EVALUATION research
- Publication
Cancer Chemotherapy & Pharmacology, 2016, Vol 78, Issue 2, p271
- ISSN
0344-5704
- Publication type
journal article
- DOI
10.1007/s00280-016-3074-y