Effects of Rovalpituzumab Tesirine on Ventricular Repolarization in Patients With Small-Cell Lung Cancer

• Type of Material: Article
• Authors: Jonathan W Goldman, University of California Los Angeles; Minal Barve, Mary Crowley Cancer Research Center; Jyoti D Patel, Northwestern University; Antoinette Wozniak, University of Pittsburgh; Afshin Dowlati, University Hospitals of Cleveland; Alexander Starodub, Riverside Peninsula Cancer Institute; Taofeek Owonikoko, Emory University; William Edenfield, Prisma Health Cancer Institute; Scott A Laurie, Ottawa Hospital Research Institute; Daniel Da Costa, AbbVie Inc; Sstwant Lally, AbbVie Inc; Martina Koch, AbbVie Inc; Matthew P Kosloski, AbbVie Inc; David Hoffman, AbbVie Inc; Grace K Dy, Roswell Park Comprehensive Cancer Center
• Language: English
• Date: 2020-12-19
• Publisher: WILEY
• Publication Version: Final Published Version
• Copyright Statement: © 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1111/cts.12928
• Title of Journal or Parent Work: CTS-CLINICAL AND TRANSLATIONAL SCIENCE
• Volume: 14
• Issue: 2
• Start Page: 664
• End Page: 670
• Keywords: ANTHRAMYCIN; Medicine, Research & Experimental; Science & Technology; Research & Experimental Medicine; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Oncology

Abstract

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.