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

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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.

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Acknowledgments

This study was sponsored by Eli Lilly and Company. Eli Lilly and Company contracted with inVentiv Health Clinical for medical writing support provided by Stacey E. Shehin, PhD, and editorial support provided by Angela C. Lorio, ELS, and Teri Tucker.

Author information

Authors and Affiliations

  1. University of Michigan, 1500 E Medical Center Drive SPC 5913, Ann Arbor, MI, 48109, USA

    David C. Smith

  2. Carolina BioOncology Institute, Huntersville, NC, USA

    John Powderly

  3. University of Pittsburgh, Pittsburgh, PA, USA

    James J. Lee

  4. Cleveland Clinic Foundation, Cleveland, OH, USA

    Dale R. Shepard

  5. Eli Lilly and Company, Solna, Sweden

    Johan Wallin

  6. Eli Lilly and Company, Indianapolis, IN, USA

    Archana Chaudhary & Grace Yi Chao

  7. Eil Lilly-NUS, Singapore, Singapore

    Wee Teck Ng

  8. Eli Lilly and Company, Windlesham, Surrey, UK

    Malcolm I. Mitchell

  9. Eli Lilly and Company, Bad Homburg, Germany

    Gerrit Grau & Raffael Kurek

  10. Yale University, New Haven, CT, USA

    Patricia LoRusso

Authors
  1. David C. Smith
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  2. John Powderly
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  9. Malcolm I. Mitchell
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Corresponding author

Correspondence to David C. Smith.

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Conflict of interest

David C. Smith received funding from Eli Lilly and Company. John Powderly received remuneration from Carolina BioOncology Institute, has consultant/advisory roles with Bristol Myers Squibb and Merck, has stock ownership in BioCytics, Lion BioTech, Juno Therapeutics, BlueBird Bio, Kite Pharma, and ZioPharm Oncology, and received funding from Bristol Myers Squibb, Genentech, EMD Serono, AstraZeneca, InCyte, MacroGenics, and Eli Lilly and Company. James J. Lee, Dale R. Shepard, and Patricia LoRusso have no conflicts to disclose. Johan Wallin, Archana Chaudhary, Grace Yi Chao, Wee Teck Ng, Gerrit Grau, and Raffael Kurek are employees of and own stock in Eli Lilly and Company. Malcolm I. Mitchell is a former employee and owns stock in Eli Lilly and Company.

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

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Smith, D.C., Powderly, J., Lee, J.J. et al. Evaluation of the effect of necitumumab on the corrected QT interval in patients with advanced solid tumors. Cancer Chemother Pharmacol 78, 271–280 (2016). https://doi.org/10.1007/s00280-016-3074-y

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  • DOI: https://doi.org/10.1007/s00280-016-3074-y

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