Brentuximab vedotin does not cause clinically relevant QTc interval prolongation in patients with CD30-positive hematologic malignancies

T. H. Han, R. Chen, R. Advani, R. B. Berryman, S. E. Smith, A. Forero-Torres, Joseph D Rosenblatt, M. R. Smith, J. Zain, N. N. Hunder, A. Engert

Research output: Contribution to journalArticle

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Abstract

Purpose: Brentuximab vedotin (ADCETRIS®), an antibody-drug conjugate, comprises an anti-CD30 antibody conjugated by a protease-cleavable linker to a microtubule-disrupting agent, monomethyl auristatin E (MMAE). In vitro studies showed that MMAE does not interfere with hERG K+ channels at clinically relevant concentrations. In pivotal phase 2 clinical trials in patients with relapsed or refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma, brentuximab vedotin has shown substantial efficacy and an acceptable safety profile. This phase 1 open-label study was designed to evaluate the effect of brentuximab vedotin on the duration of cardiac ventricular repolarization. Methods: Patients with CD30-positive hematologic malignancies were treated with 1.8 mg/kg brentuximab vedotin by intravenous infusion every 3 weeks for up to 16 cycles. The primary endpoint was the change from baseline to Cycle 1 Days 2, 3, and 4 in the duration of ventricular repolarization using Fridericia's corrected QT interval (QTcF). Results: There was no clinically meaningful change from baseline in the duration of ventricular repolarization as measured by QTcF in the 46 evaluable patients out of 52 total patients treated with brentuximab vedotin. There was no evidence of treatment-emergent cardiac safety abnormalities. Brentuximab vedotin was generally well tolerated with a response rate and an adverse event profile consistent with prior studies. Conclusion: There is no significant prolongation of the QT/QTc interval with brentuximab vedotin in patients with CD30-positive hematologic malignancies.

Original languageEnglish
Pages (from-to)241-249
Number of pages9
JournalCancer Chemotherapy and Pharmacology
Volume72
Issue number1
DOIs
StatePublished - Jul 1 2013

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Hematologic Neoplasms
Anaplastic Large-Cell Lymphoma
Safety
Antibodies
cAC10-vcMMAE
Hodgkin Disease
Intravenous Infusions
Microtubules
Refractory materials
Labels
Anti-Idiotypic Antibodies
Peptide Hydrolases
Clinical Trials
Pharmaceutical Preparations

Keywords

  • Antibody-drug conjugate
  • Brentuximab vedotin
  • CD30-positive hematologic malignancies
  • QT interval

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Toxicology

Cite this

Brentuximab vedotin does not cause clinically relevant QTc interval prolongation in patients with CD30-positive hematologic malignancies. / Han, T. H.; Chen, R.; Advani, R.; Berryman, R. B.; Smith, S. E.; Forero-Torres, A.; Rosenblatt, Joseph D; Smith, M. R.; Zain, J.; Hunder, N. N.; Engert, A.

In: Cancer Chemotherapy and Pharmacology, Vol. 72, No. 1, 01.07.2013, p. 241-249.

Research output: Contribution to journalArticle

Han, TH, Chen, R, Advani, R, Berryman, RB, Smith, SE, Forero-Torres, A, Rosenblatt, JD, Smith, MR, Zain, J, Hunder, NN & Engert, A 2013, 'Brentuximab vedotin does not cause clinically relevant QTc interval prolongation in patients with CD30-positive hematologic malignancies', Cancer Chemotherapy and Pharmacology, vol. 72, no. 1, pp. 241-249. https://doi.org/10.1007/s00280-013-2192-z
Han, T. H. ; Chen, R. ; Advani, R. ; Berryman, R. B. ; Smith, S. E. ; Forero-Torres, A. ; Rosenblatt, Joseph D ; Smith, M. R. ; Zain, J. ; Hunder, N. N. ; Engert, A. / Brentuximab vedotin does not cause clinically relevant QTc interval prolongation in patients with CD30-positive hematologic malignancies. In: Cancer Chemotherapy and Pharmacology. 2013 ; Vol. 72, No. 1. pp. 241-249.
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abstract = "Purpose: Brentuximab vedotin (ADCETRIS{\circledR}), an antibody-drug conjugate, comprises an anti-CD30 antibody conjugated by a protease-cleavable linker to a microtubule-disrupting agent, monomethyl auristatin E (MMAE). In vitro studies showed that MMAE does not interfere with hERG K+ channels at clinically relevant concentrations. In pivotal phase 2 clinical trials in patients with relapsed or refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma, brentuximab vedotin has shown substantial efficacy and an acceptable safety profile. This phase 1 open-label study was designed to evaluate the effect of brentuximab vedotin on the duration of cardiac ventricular repolarization. Methods: Patients with CD30-positive hematologic malignancies were treated with 1.8 mg/kg brentuximab vedotin by intravenous infusion every 3 weeks for up to 16 cycles. The primary endpoint was the change from baseline to Cycle 1 Days 2, 3, and 4 in the duration of ventricular repolarization using Fridericia's corrected QT interval (QTcF). Results: There was no clinically meaningful change from baseline in the duration of ventricular repolarization as measured by QTcF in the 46 evaluable patients out of 52 total patients treated with brentuximab vedotin. There was no evidence of treatment-emergent cardiac safety abnormalities. Brentuximab vedotin was generally well tolerated with a response rate and an adverse event profile consistent with prior studies. Conclusion: There is no significant prolongation of the QT/QTc interval with brentuximab vedotin in patients with CD30-positive hematologic malignancies.",
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AU - Forero-Torres, A.

AU - Rosenblatt, Joseph D

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