Effects of Rovalpituzumab Tesirine on Ventricular Repolarization in Patients With Small‐Cell Lung Cancer
Small cell lung cancer (SCLC) is a leading cause of cancer death worldwide, with few treatment options. Rovalpituzumab tesirine (Rova‐T) is an antibody‐drug conjugate that targets delta‐like 3 on SCLC cells to deliver a cytotoxic payload directly to tumor cells. In this study, the cardiac safety pro...
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doaj-accac0c4d8ab4b6a908935af63ca37f02021-03-25T15:37:46ZengWileyClinical and Translational Science1752-80541752-80622021-03-0114266467010.1111/cts.12928Effects of Rovalpituzumab Tesirine on Ventricular Repolarization in Patients With Small‐Cell Lung CancerJonathan W. Goldman0Minal Barve1Jyoti D. Patel2Antoinette Wozniak3Afshin Dowlati4Alexander Starodub5Taofeek K. Owonikoko6William Edenfield7Scott A. Laurie8Daniel Da Costa9Satwant Lally10Martina Koch11Matthew P. Kosloski12David Hoffman13Grace K. Dy14David Geffen School of Medicine at UCLA Los Angeles California USAMary Crowley Cancer Research Center Dallas Texas USALurie Cancer Center of Northwestern University Chicago Illinois USAHillman Cancer Center at University of Pittsburgh Medical Center Pittsburgh Pennsylvania USAUniversity Hospitals Cleveland Medical Center Cleveland Ohio USARiverside Peninsula Cancer Institute Newport News Virginia USAWinship Cancer Institute of Emory University Atlanta Georgia USAPrisma Health Cancer Institute Greenville South Carolina USAOttawa Hospital Research Institute Ottawa Ontario CanadaAbbVie, Inc. Illinois North Chicago USAAbbVie, Inc. Illinois North Chicago USAAbbVie, Inc. Illinois North Chicago USAAbbVie, Inc. Illinois North Chicago USAAbbVie, Inc. Illinois North Chicago USARoswell Park Comprehensive Cancer Center Buffalo New York USASmall cell lung cancer (SCLC) is a leading cause of cancer death worldwide, with few treatment options. Rovalpituzumab tesirine (Rova‐T) is an antibody‐drug conjugate that targets delta‐like 3 on SCLC cells to deliver a cytotoxic payload directly to tumor cells. In this study, the cardiac safety profile of Rova‐T was assessed by evaluating changes in QT interval, electrocardiogram (ECG) waveform, heart rate, and proarrhythmic adverse events (AEs) after treatment with Rova‐T in patients with previously treated extensive‐stage SCLC. Patients underwent ECG monitoring for 2 weeks after each of 2 i.v. infusions of 0.3 mg/kg Rova‐T over 30 minutes, administered 6 weeks apart. Forty‐six patients received at least one dose of Rova‐T. At the geometric mean Rova‐T maximum serum concentration of 7,940 ng/mL, ECG monitoring showed no significant changes in the Fridericia‐corrected QT (QTcF) interval; the upper limit of the 2‐sided 90% confidence interval did not exceed 10 msec for any time point. There were no clinically significant changes in QRS or PR intervals, ECG waveforms, or heart rate after Rova‐T administration. All patients experienced a treatment‐emergent AE (TEAE); 78% had a grade ≥ 3 TEAE, 59% had a serious TEAE, and 41% had a cardiac‐related TEAE. The TEAEs that might signal proarrhythmia tendencies were uncommon. Confirmed partial responses were observed in 24% of patients. Based on the evaluation of ECG data collected in this study from patients treated with Rova‐T at 0.3 mg/kg i.v. administered every 6 weeks, a QTcF effect of clinical concern can be excluded.https://doi.org/10.1111/cts.12928 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jonathan W. Goldman Minal Barve Jyoti D. Patel Antoinette Wozniak Afshin Dowlati Alexander Starodub Taofeek K. Owonikoko William Edenfield Scott A. Laurie Daniel Da Costa Satwant Lally Martina Koch Matthew P. Kosloski David Hoffman Grace K. Dy |
spellingShingle |
Jonathan W. Goldman Minal Barve Jyoti D. Patel Antoinette Wozniak Afshin Dowlati Alexander Starodub Taofeek K. Owonikoko William Edenfield Scott A. Laurie Daniel Da Costa Satwant Lally Martina Koch Matthew P. Kosloski David Hoffman Grace K. Dy Effects of Rovalpituzumab Tesirine on Ventricular Repolarization in Patients With Small‐Cell Lung Cancer Clinical and Translational Science |
author_facet |
Jonathan W. Goldman Minal Barve Jyoti D. Patel Antoinette Wozniak Afshin Dowlati Alexander Starodub Taofeek K. Owonikoko William Edenfield Scott A. Laurie Daniel Da Costa Satwant Lally Martina Koch Matthew P. Kosloski David Hoffman Grace K. Dy |
author_sort |
Jonathan W. Goldman |
title |
Effects of Rovalpituzumab Tesirine on Ventricular Repolarization in Patients With Small‐Cell Lung Cancer |
title_short |
Effects of Rovalpituzumab Tesirine on Ventricular Repolarization in Patients With Small‐Cell Lung Cancer |
title_full |
Effects of Rovalpituzumab Tesirine on Ventricular Repolarization in Patients With Small‐Cell Lung Cancer |
title_fullStr |
Effects of Rovalpituzumab Tesirine on Ventricular Repolarization in Patients With Small‐Cell Lung Cancer |
title_full_unstemmed |
Effects of Rovalpituzumab Tesirine on Ventricular Repolarization in Patients With Small‐Cell Lung Cancer |
title_sort |
effects of rovalpituzumab tesirine on ventricular repolarization in patients with small‐cell lung cancer |
publisher |
Wiley |
series |
Clinical and Translational Science |
issn |
1752-8054 1752-8062 |
publishDate |
2021-03-01 |
description |
Small cell lung cancer (SCLC) is a leading cause of cancer death worldwide, with few treatment options. Rovalpituzumab tesirine (Rova‐T) is an antibody‐drug conjugate that targets delta‐like 3 on SCLC cells to deliver a cytotoxic payload directly to tumor cells. In this study, the cardiac safety profile of Rova‐T was assessed by evaluating changes in QT interval, electrocardiogram (ECG) waveform, heart rate, and proarrhythmic adverse events (AEs) after treatment with Rova‐T in patients with previously treated extensive‐stage SCLC. Patients underwent ECG monitoring for 2 weeks after each of 2 i.v. infusions of 0.3 mg/kg Rova‐T over 30 minutes, administered 6 weeks apart. Forty‐six patients received at least one dose of Rova‐T. At the geometric mean Rova‐T maximum serum concentration of 7,940 ng/mL, ECG monitoring showed no significant changes in the Fridericia‐corrected QT (QTcF) interval; the upper limit of the 2‐sided 90% confidence interval did not exceed 10 msec for any time point. There were no clinically significant changes in QRS or PR intervals, ECG waveforms, or heart rate after Rova‐T administration. All patients experienced a treatment‐emergent AE (TEAE); 78% had a grade ≥ 3 TEAE, 59% had a serious TEAE, and 41% had a cardiac‐related TEAE. The TEAEs that might signal proarrhythmia tendencies were uncommon. Confirmed partial responses were observed in 24% of patients. Based on the evaluation of ECG data collected in this study from patients treated with Rova‐T at 0.3 mg/kg i.v. administered every 6 weeks, a QTcF effect of clinical concern can be excluded. |
url |
https://doi.org/10.1111/cts.12928 |
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