David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Mary Crowley Cancer Research Center, Dallas, Texas, USA.
Clin Transl Sci. 2021 Mar;14(2):664-670. doi: 10.1111/cts.12928. Epub 2020 Dec 19.
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.
小细胞肺癌（SCLC）是全球癌症死亡的主要原因，治疗选择有限。Rovalpituzumab tesirine（Rova-T）是一种抗体药物偶联物，针对 SCLC 细胞上的 delta-like 3 靶向，将细胞毒性有效载荷直接递送至肿瘤细胞。在这项研究中，通过评估 Rova-T 治疗后 QT 间期、心电图（ECG）波形、心率和致心律失常不良事件（AE）的变化，评估了 Rova-T 的心脏安全性。在 6 周的间隔内，每 2 周静脉输注 2 次 0.3 mg/kg 的 Rova-T，每次输注 30 分钟，每次输注后患者接受 2 周的心电图监测。46 例患者至少接受了一剂 Rova-T。在几何平均 Rova-T 最大血清浓度为 7940ng/mL 时，心电图监测显示 Fridericia 校正 QT（QTcF）间期没有显著变化；任何时间点的双侧 90%置信区间上限均未超过 10 msec。给药后 QRS 或 PR 间隔、心电图波形或心率无临床显著变化。所有患者均发生治疗后出现的 AE（TEAE）；78%的患者有≥3 级 TEAE，59%的患者有严重的 TEAE，41%的患者有与心脏相关的 TEAE。可能提示致心律失常倾向的 TEAEs 并不常见。确认的部分缓解率为 24%。基于 Rova-T 在 0.3 mg/kg 静脉输注、每 6 周一次的治疗中，从接受治疗的患者中收集的 ECG 数据评估，排除了具有临床关注的 QTcF 效应。
