Third Department of Internal Medicine, Wakayama Medical University, Wakayama City, Japan.
Third Department of Internal Medicine, Wakayama Medical University, Wakayama City, Japan.
Clin Lung Cancer. 2018 Nov;19(6):e871-e874. doi: 10.1016/j.cllc.2018.08.001. Epub 2018 Aug 22.
Epidermal growth factor receptor (EGFR) T790M mutation is the most frequent mechanism of resistance among patients with progression during EGFR-tyrosine kinase inhibitor (TKI) therapy. A third-generation EGFR-TKI, osimertinib, demonstrated durable efficacy with mild adverse events in a phase III trial and is considered a novel standard regimen. The tolerability of osimertinib monotherapy has allowed for the development of a more efficacious combination regimen. Preclinical and clinical study data have suggested that vascular endothelial growth factor inhibition can enhance EGFR-TKI activity with tolerable toxicity.
The aim of the present single-arm, phase Ib study is to assess the tolerability of osimertinib combined with ramucirumab in patients with EGFR-mutated, T790M lung cancer with progression during EGFR-TKI therapy. The primary endpoint is to assess the safety of osimertinib plus ramucirumab at a fixed dose. The secondary endpoints are the overall response rate, progression-free survival, overall survival, and safety. Six patients will be enrolled in the trial.
表皮生长因子受体（EGFR）T790M 突变是 EGFR-酪氨酸激酶抑制剂（TKI）治疗期间疾病进展患者最常见的耐药机制。第三代 EGFR-TKI 奥希替尼在 III 期临床试验中显示出持久的疗效和轻微的不良反应，被认为是一种新型的标准治疗方案。奥希替尼单药治疗的耐受性允许开发更有效的联合治疗方案。临床前和临床研究数据表明，血管内皮生长因子抑制可以增强 EGFR-TKI 的活性，同时具有可耐受的毒性。
本单臂、Ib 期研究的目的是评估奥希替尼联合雷莫芦单抗在 EGFR 突变、T790M 肺癌患者中的耐受性，这些患者在 EGFR-TKI 治疗期间发生进展。主要终点是评估奥希替尼联合雷莫芦单抗固定剂量的安全性。次要终点是总缓解率、无进展生存期、总生存期和安全性。该试验将招募 6 名患者。
