title: Brentuximab vedotin does not cause clinically relevant QTc interval prolongation in patients with CD30-positive hematologic malignancies.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  There is no significant prolongation of the QT/QTc interval with brentuximab vedotin in patients with CD30-positive hematologic malignancies.
authors.affiliation: Seattle Genetics, Inc., Bothell, WA 98021, USA. than@seagen.com
authors.forename: T H
authors.initials: TH
authors.lastname: Han
authors.forename: R
authors.initials: R
authors.lastname: Chen
authors.forename: R
authors.initials: R
authors.lastname: Advani
authors.forename: R B
authors.initials: RB
authors.lastname: Berryman
authors.forename: S E
authors.initials: SE
authors.lastname: Smith
authors.forename: A
authors.initials: A
authors.lastname: Forero-Torres
authors.forename: J D
authors.initials: JD
authors.lastname: Rosenblatt
authors.forename: M R
authors.initials: MR
authors.lastname: Smith
authors.forename: J
authors.initials: J
authors.lastname: Zain
authors.forename: N N
authors.initials: NN
authors.lastname: Hunder
authors.forename: A
authors.initials: A
authors.lastname: Engert
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D000079963:Brentuximab Vedotin; D054715:Cardiotoxins / Q000009:adverse effects / Q000627:therapeutic use; D004342:Drug Hypersensitivity / Q000276:immunology; D015716:Electrocardiography, Ambulatory / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D019337:Hematologic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006689:Hodgkin Disease / Q000097:blood / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D017730:Ki-1 Antigen / Q000097:blood / Q000378:metabolism*; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000503:physiopathology; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D054715:Cardiotoxins; D018796:Immunoconjugates; D017730:Ki-1 Antigen; D000079963:Brentuximab Vedotin