National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
Wakayama Medical University Hospital, Wakayama, Wakayama, Japan.
Lung Cancer. 2019 Sep;135:145-150. doi: 10.1016/j.lungcan.2019.07.025. Epub 2019 Jul 24.
Rovalpituzumab tesirine (Rova-T™) is an antibody-drug conjugate that targets delta-like protein 3 (DLL3) on small cell lung cancer (SCLC) tumors, is internalized and releases the toxin pyrrolobenzodiazepine to induce cell death. This open label phase I study was the first study of Rova-T in Japanese patients. The aim of this study was to evaluate, safety, pharmacokinetics, and preliminary efficacy of Rova-T in Japanese patients with advanced recurrent SCLC.
Patients received Rova-T (0.2 or 0.3 mg/kg) by intravenous infusion on Day (D) 1 of each 6-week cycle for 2 doses and dexamethasone (8 mg BID oral) on D-1, D1, and D2 of each 6-week cycle. Retreatment with Rova-T was permitted for patients who tolerated their initial doses and then progressed after disease control (defined as stable disease or better) was observed for at least 12 weeks after their last dose of Rova-T.
Rova-T exhibited toxicity that was generally manageable in Japanese patients (N = 29). No dose-limiting toxicities were experienced. The most common treatment-related adverse events (≥25% of patients, all grades) were platelet count decreased, pleural effusion, peripheral edema, aspartate aminotransferase increased, white blood cell count decreased, neutrophil count decreased, alanine aminotransferase increased, hypoalbuminaemia, anemia and decreased appetite. Safety and pharmacokinetics exposures were similar to previous observations in non-Japanese populations. Per investigator assessment of DLL3 high patients, 17% (3/18) had confirmed partial responses, and the disease control rate was 56%, mPFS was 2.9 months, and mOS was 7.4 months.
These preliminary data support further exploration of Rova-T treatment in Japanese patients with SCLC in global studies. This trial was registered with ClinicalTrials.gov as NCT03086239.
罗瓦替曲单抗（Rova-T）是一种针对小细胞肺癌（SCLC）肿瘤上的 Delta 样蛋白 3（DLL3）的抗体药物偶联物，可被内吞并释放毒素吡咯并苯并二氮杂卓，从而诱导细胞死亡。这项开放标签的 I 期研究是 Rova-T 在日本患者中的首次研究。本研究旨在评估 Rova-T 在日本晚期复发性 SCLC 患者中的安全性、药代动力学和初步疗效。
患者每 6 周周期的第 1 天接受 Rova-T（0.2 或 0.3mg/kg）静脉输注，每 6 周周期的第 1 天、第 1 天和第 2 天接受地塞米松（8mg BID 口服）。在初始剂量耐受且在最后一次 Rova-T 剂量后至少 12 周疾病控制（定义为稳定疾病或更好）后进展的患者中，可以重新使用 Rova-T。
Rova-T 在日本患者中表现出可管理的毒性（N=29）。未观察到剂量限制毒性。最常见的治疗相关不良事件（≥25%的患者，所有级别）为血小板计数降低、胸腔积液、外周水肿、天门冬氨酸氨基转移酶升高、白细胞计数降低、中性粒细胞计数降低、丙氨酸氨基转移酶升高、低白蛋白血症、贫血和食欲下降。安全性和药代动力学暴露与非日本人群中的先前观察结果相似。根据研究者对 DLL3 高表达患者的评估，17%（3/18）的患者有确认的部分缓解，疾病控制率为 56%，mPFS 为 2.9 个月，mOS 为 7.4 个月。
这些初步数据支持在全球研究中进一步探索 Rova-T 治疗日本 SCLC 患者的应用。该试验在 ClinicalTrials.gov 上注册为 NCT03086239。
