新辅助伯福替尼联合伏罗尼布治疗可切除II-IIIB期EGFR突变非小细胞肺癌：一项前瞻性、单臂I/II期试验的研究方案
Neoadjuvant befotertinib plus vorolanib in resectable stage II-IIIB EGFR-mutant NSCLC: a study protocol for the prospective, single-arm phase I/II trial.
作者
作者单位
- Department of Thoracic Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China.
摘要
中文
新辅助靶向治疗是可切除的非小细胞肺癌（NSCLC）伴表皮生长因子受体（EGFR）突变的一种有前景的策略，但单用EGFR-酪氨酸激酶抑制剂（TKI）的病理退缩仍不理想。伯福替尼（Befotertinib）是第三代EGFR-TKI，而伏罗尼布（Vorolanib）是多靶点抗血管生成TKI。联合抑制EGFR和血管内皮生长因子受体（VEGFR）通路可能增强肿瘤退缩，同时保留手术可行性。这是一项前瞻性、开放标签、单臂I/II期研究，入组临床可切除II-IIIB期且携带敏感性EGFR 19号外显子缺失和/或21号外显子L858R突变的NSCLC患者。I期采用3+3剂量递增设计，以确定新辅助伯福替尼联合伏罗尼布的最大耐受剂量和推荐II期剂量。II期采用两阶段设计，评估两个21天新辅助周期后的主要病理反应。患者在新辅助治疗后接受影像学评估，然后在最后一次治疗剂量后4-6周接受根治性手术。次要终点包括病理完全缓解、R0切除率、客观缓解率、疾病控制率、安全性、无病生存期和总生存期。该试验将前瞻性探索第三代EGFR抑制联合抗血管生成治疗在可切除II-IIIB期EGFR突变NSCLC中的可行性、安全性和初步活性。该研究可能有助于确定强化新辅助靶向治疗是否能改善这一分子选择人群的病理退缩。中国临床试验注册中心（ChiCTR2500103324）。
English
Neoadjuvant targeted therapy is a promising strategy for resectable non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation, but pathological regression remains suboptimal with EGFR-tyrosine kinase inhibitor (TKI) monotherapy. Befotertinib is a third-generation EGFR-TKI, whereas vorolanib is a multi-target antiangiogenic TKI. Combined EGFR and vascular endothelial growth factor receptor (VEGFR) pathway inhibition may enhance tumor regression while preserving surgical feasibility. This is a prospective, open-label, single-arm phase I/II study enrolling NSCLC patients with clinically resectable stage II-IIIB harboring sensitizing EGFR exon 19 deletion and/or exon 21 L858R mutations. Phase I uses a 3+3 dose-escalation design to determine the maximum tolerated dose and recommended phase II dose of neoadjuvant befotertinib plus vorolanib. Phase II adopts a two-stage design and evaluates major pathological response after two 21-day neoadjuvant cycles. Patients undergo radiographic assessment after neoadjuvant therapy, followed by radical surgery 4-6 weeks after the last treatment dose. Secondary endpoints include pathological complete response, R0 resection rate, objective response rate, disease control rate, safety, disease-free survival, and overall survival. This trial will prospectively explore the feasibility, safety, and preliminary activity of combined third-generation EGFR inhibition and antiangiogenic therapy in resectable stage II-IIIB EGFR-mutant NSCLC. The study may help define whether intensification of neoadjuvant targeted therapy can improve pathological regression in this molecularly selected population. Chinese Clinical Trial Registry (ChiCTR2500103324).
分类与指标
- 研究类型
- 临床研究
- 病种
- 肺癌
- JCR 分区
- Q2
- 影响因子
- 3.4
- 新锐分区
- 3区