SH-1028 治疗 EGFR T790M 阳性 NSCLC 患者的疗效和安全性：一项多中心、单臂、开放标签、Ⅱ期临床试验。
Efficacy and Safety of SH-1028 in Patients With EGFR T790M-Positive NSCLC: A Multicenter, Single-Arm, Open-Label, Phase 2 Trial.
机构信息
Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
Department of Integrated Chinese and Western Medicine, Henan Provincial Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
出版信息
J Thorac Oncol. 2022 Oct;17(10):1216-1226. doi: 10.1016/j.jtho.2022.06.013. Epub 2022 Jul 5.
INTRODUCTION
As a novel third-generation EGFR tyrosine kinase inhibitor (TKI), SH-1028 (formerly oritinib) is developed to inhibit both sensitizing EGFR mutations and EGFR T790M mutation.
METHODS
This was a multicenter, single-arm, open-label, phase 2 trial (NCT03823807). Eligible patients were those with advanced NSCLC with centrally confirmed EGFR T790M mutation who progressed after first- or second-generation EGFR TKIs or with primary EGFR T790M mutations. Each patient received SH-1028 tablets orally at 200 mg/d until disease progression or intolerable toxicity. Tumor response was evaluated every 6 weeks per the Response Evaluation Criteria in Solid Tumors, version 1.1. The primary end point was objective response rate by an independent review committee. The secondary end points were progression-free survival, overall survival (OS), disease control rate, safety, and so on.
RESULTS
A total of 286 patients with EGFR T790M-positive advanced NSCLC were enrolled in this study, including 59 patients in part A (dose-verification study) and 227 patients in part B (second-line registration study). By data cutoff on September 17, 2021, the independent review committee-assessed objective response rate was 55.9% (95% confidence interval [CI]: 42.4-68.8) in part A and 60.4% (95% CI: 53.7-66.8) in part B. The median progression-free survival was 12.4 months (95% CI: 8.3-20.8) in part A and 12.6 months (95% CI: 9.7-15.3) in part B. The median OS was 26.0 months (95% CI: 23.3-not reached) in part A, and OS was immature in part B. Among the 286 patients, 44 of them experienced at least one grade 3 or higher treatment-related adverse event, with the most common ones as increased serum creatinine phosphokinase level (13 [4.5%]), diarrhea (six [2.1%]), and prolonged QT interval (three [1.0%]). Treatment-related skin rash was reported in 26 patients (9.1%), all grade 1 or 2. There was no interstitial lung disease reported in this study.
CONCLUSIONS
SH-1028 is efficacious and tolerable in second-line treatment of patients with advanced NSCLC with positive EGFR T790M.
简介
SH-1028（前身为奥替尼）作为一种新型第三代 EGFR 酪氨酸激酶抑制剂（TKI），旨在抑制敏感 EGFR 突变和 EGFR T790M 突变。
方法
这是一项多中心、单臂、开放标签、2 期临床试验（NCT03823807）。入组标准为：经中心确认为 EGFR T790M 突变的局部晚期 NSCLC 患者，在接受第一代或第二代 EGFR TKI 治疗后进展，或存在原发性 EGFR T790M 突变。每位患者接受 SH-1028 片 200mg/d 口服治疗，直至疾病进展或出现无法耐受的毒性。每 6 周根据实体瘤反应评价标准 1.1 评估肿瘤反应。主要终点为独立评审委员会评估的客观缓解率。次要终点包括无进展生存期、总生存期（OS）、疾病控制率、安全性等。
结果
共纳入 286 例 EGFR T790M 阳性局部晚期 NSCLC 患者，其中 59 例患者入组 A 部分（剂量验证研究），227 例患者入组 B 部分（二线注册研究）。截至 2021 年 9 月 17 日数据截止时，独立评审委员会评估的 A 部分客观缓解率为 55.9%（95%CI：42.4-68.8），B 部分为 60.4%（95%CI：53.7-66.8）。A 部分的中位无进展生存期为 12.4 个月（95%CI：8.3-20.8），B 部分为 12.6 个月（95%CI：9.7-15.3）。A 部分的中位 OS 为 26.0 个月（95%CI：23.3-未达到），B 部分 OS 不成熟。在 286 例患者中，44 例（15.3%）至少发生 1 次 3 级或以上治疗相关不良事件，最常见的是血清肌酸磷酸激酶升高（13 例[4.5%]）、腹泻（6 例[2.1%]）和 QT 间期延长（3 例[1.0%]）。治疗相关皮疹报告 26 例（9.1%），均为 1 级或 2 级。本研究无间质性肺病报告。
结论
SH-1028 在 EGFR T790M 阳性晚期 NSCLC 二线治疗中具有疗效和可耐受性。
Zotero 插件