SH-1028对EGFR T790M阳性非小细胞肺癌患者的疗效和安全性

SCI

24 July 2022

Efficacy and safety of SH-1028 in patients with EGFR T790M positive non-small-cell lung cancer: a multicenter, single-arm, open-label, phase 2 trial

（ J Thorac Oncol IF：20.121）

• Xiong A, Ren S, Liu H, Miao L, Wang L, Chen J, Li W, Li R, Wang X, Lu Z, Wang D, Wu X, Liu Z, Xing L, Mao Y, Liu C, Zeng A, Niu H, Du Y, Sun Y, Pan Y, Hu Y, Zhang X, Chen X, Ma Z, Li N, Zhang J, Zhao M, Li X, Ye F, Li M, Yu G, Zhang X, Min J, Han D, Li J, Zhou C. Efficacy and safety of SH-1028 in patients with EGFR T790M positive non-small-cell lung cancer: a multicenter, single-arm, open-label, phase 2 trial. J Thorac Oncol. 2022 Jul 4:S1556-0864(22)00327-6. doi: 10.1016/j.jtho.2022.06.013. Epub ahead of print. PMID: 35798241.

Introduction 简介

As a novel third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), SH-1028 (formerly oritinib) is developed to inhibit both sensitizing EGFR mutations and EGFR T790M mutation.

作为一种新型的第三代表皮生长因子受体酪氨酸激酶抑制剂（EGFR TKI），SH-1028（原奥瑞替尼）被开发出来，可以抑制敏感的EGFR突变和EGFR T790M突变。

Methods 方法

This was a multicenter, single-arm, open-label, phase 2 trial (NCT03823807). Eligible patients were advanced NSCLC patients 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/day until disease progression or intolerable toxicity. Tumor response was evaluated every 6 weeks per the RECIST 1.1. The primary endpoint was objective response rate (ORR) by Independent Review Committee (IRC). The secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), safety, etc. 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 cut-off on September 17, 2021, the IRC-assessed ORR 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 PFS 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∼NR) 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 (TRAE), with the most common ones as increased serum creatine phosphokinase (13 [4.5%]), diarrhea (6 [2.1%]), and prolonged QT interval (3 [1.0%]). Treatment-related skin rash was reported in 26 (9.1%) patients, all grade 1 or 2. There was no interstitial lung disease reported in this study.

这是一项多中心、单臂、开放标签、2期试验（NCT03823807）。符合条件的患者是具有中心确认的EGFR T790M突变的晚期NSCLC患者，这些患者在使用第一代或第二代EGFR TKIs后出现进展，或具有原发性EGFR T790M突变。每位患者接受SH-1028片剂口服，剂量为200毫克/天，直到疾病进展或无法忍受的毒性。根据RECIST 1.1标准，每6周对肿瘤反应进行评估。主要终点是独立审查委员会（IRC）的客观反应率（ORR）。次要终点是无进展生存期（PFS）、总生存期（OS）、疾病控制率（DCR）、安全性等。结果：共有286名EGFR T790M阳性的晚期NSCLC患者被纳入本研究，包括A部分（剂量验证研究）的59名患者和B部分（二线注册研究）的227名患者。到2021年9月17日数据截止时，IRC评估的ORR在A部分为55.9%（95%置信区间[CI]：42.4∼68.8），B部分为60.4%（95%CI：53.7∼66.8). A部分的中位PFS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∼NR），B部分的OS则不成熟。在286名患者中，有44名患者至少经历了一次3级或以上的治疗相关不良事件（TRAE），最常见的是血清肌酸磷酸激酶升高（13[4.5%]），腹泻（6[2.1%]）和QT间期延长（3[1.0%]）。有26名（9.1%）患者报告了与治疗相关的皮疹，均为1或2级。本研究中没有间质性肺病的报告。

Conclusions 结论

SH-1028 is efficacious and tolerable in second-line treatment of advanced NSCLC patients with positive EGFR T790M. 

SH-1028在EGFR T790M阳性的晚期NSCLC患者的二线治疗中是有效和可耐受的。