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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 664-670 |
| Number of pages | 7 |
| Journal | Clinical and Translational Science |
| Volume | 14 |
| Issue number | 2 |
| DOIs | |
| State | Published - Mar 2021 |
Funding
The authors thank the patients and their families, study coordinators, and support staff. AbbVie provided financial support for this study and participated in the design, study conduct, and analysis and interpretation of data, as well as the writing, review, and approval of this manuscript. Medical writing assistance was provided by Allison Cherry, PhD, of Bio Connections, LLC, and funded by AbbVie. AbbVie provided financial support for this study and participated in the design, study conduct, and analysis and interpretation of the data, as well as the writing, review, and approval of the article. All authors had full access to the study data and were involved in the data gathering, analysis, review, interpretation, and article preparation and approval. No honoraria or payments were made for authorship.
ASJC Scopus subject areas
- General Neuroscience
- General Biochemistry, Genetics and Molecular Biology
- General Pharmacology, Toxicology and Pharmaceutics
