Yang JJ, Zhang Y, Wu L, Hu J, Wang ZH, Chen JH, Fan Y, Lin G, Wang QM, Yao Y, Zhao J, Chen Y, Fang J, Song Y, Zhang W, Cheng Y, Guo RH, Li XY, Shi HP, Xue WZ, Han D, Zhang PL, Wu YL. Vebreltinib for Advanced Non-Small Cell Lung Cancer Harboring c-Met Exon 14 Skipping Mutation: A Multicenter, Single-Arm, Phase II KUNPENG Study. J Clin Oncol. 2024 Nov;42(31):3680-3691. doi: 10.1200/JCO.23.02363. Epub 2024 Jul 26. PMID: 39058972; PMCID: PMC11527384.
Wu YL, Yao Y, Yang JJ, Wu L, Zhang W, Wang Y, Xu HP, Song Y, Zhang Y, Zhao J, Chen JH, Wang ZH, Wang QM, Hu J, Li XY, Fan Y, Chen Y, Fang J, Han D, Xue WZ, Liu SM, Zhou Q, Zhang PL, Shi HP. Vebreltinib in MET amplification-driven advanced non-small-cell lung cancer (KUNPENG): a single-arm, multi-cohort, multicentre, phase 2 study. Lancet Oncol. 2026 Jan;27(1):36-44. doi: 10.1016/S1470-2045(25)00594-7. Epub 2025 Dec 6. PMID: 41365311.
伯瑞替尼（vebreltinib，又称bozitinib、APL-101、PLB-1001 或CBT-101）是一种强效的、高选择性的c-MET 抑制剂。为了评估伯瑞替尼在伴有c-Met 改变的、局部晚期或转移性NSCLC 患者中的疗效和安全性，该项多中心、多队列、开放标签、单臂、Ⅱ期试验（KUNPENG） 于2020 年1月至2022 年8 月自17 个中心纳入c-Met 表达异常的、局部晚期或转移性NSCLC 患者。队列1 包括携带METex14 的、未接受过MET抑制剂的NSCLC 患者。在28 天的周期中，患者应用伯瑞替尼200mg bid。
主要终点是客观缓解率（ORR）。关键的次要终点是缓解持续时间（DoR）。
结果显示，截至2022 年8 月9日，52 例患者被纳入队列1，其中35 例（67.3%）为初治患者。ORR为75%（95%CI 61.1%~86%）。在初治患者中，ORR 为77.1%（95%CI59.9%~89.6%），在经治患者中为70.6%（95%CI 44.0%~89.7%）。疾病控制率为96.2%，中位DoR 为15.9 个月，中位无进展生存期为14.1 个月，中位总生存期为20.7个月。
最常见的治疗相关不良事件为外周水肿（82.7%）、QT 间期延长（30.8%）和血清肌酐水平升高（28.8%）。
在MET 第14 号外显子跳跃突变（METex14）的、局部晚期或转移性非小细胞肺癌（NSCLC）患者中，伯瑞替尼（vebreltinib，又称bozitinib、APL-101、PLB-1001 或CBT-101）显示出有希望的疗效和良好的安全性。
Background: MET amplification is recognised as a de novo driver alteration in non-small-cell lung cancer (NSCLC) but treatment responses with existing MET inhibitors remain largely unsatisfactory. We aimed to investigate the antitumour activity and safety of vebreltinib, a potent and highly selective MET inhibitor, in patients with MET amplification-driven NSCLC.
Methods: KUNPENG was a multicentre, multi-cohort, single-arm, phase 2 trial conducted across 17 hospitals in China, in patients with locally advanced or metastatic NSCLC with MET dysregulation. Patients were eligible if they were MET inhibitor-naive, aged 18 years or older with MET amplification-driven NSCLC (gene copy number of six or higher), and progressed after previous standard chemotherapy or were ineligible for chemotherapy (cohort 2) or refused chemotherapy (cohort 3). Patients received 200 mg vebreltinib orally twice daily until disease progression or intolerable toxicity. The primary endpoint was the objective response rate, assessed by a masked independent review committee in the full analysis set. The study was amended to merge cohorts 2 and 3 due to slow accrual and was closed to enrolment on Nov 14, 2023. This trial is registered with ClinicalTrials.gov (NCT04258033).
Findings: Between Jan 17, 2020, and Nov 14, 2023, 145 patients were enrolled; of these, 86 patients (30 chemotherapy-treated and 56 untreated) from cohorts 2 and 3 were included in the current analysis. The median age was 65 years (range 48-82; IQR 59-71), 77 (90%) patients were male, and nine (10%) were female. All patients were Chinese. 42 patients had partial response, resulting in an objective response rate of 48·8% (42 of 86; 95% CI 38·3-59·4) per masked independent review committee. The median follow-up was 18·6 months (IQR 15·7-37·3). The incidence of grade 3 or worse treatment-related adverse events was 31% (27 of 86), predominantly abnormal liver function terms reported by the investigators (eight [9%]). Serious adverse events related to treatment were reported by 16 (19%) patients. 11 treatment-emergent adverse events leading to death occurred, of which one patient died of abnormal liver function, which was possibly related to vebreltinib treatment.
Interpretation: Vebreltinib showed antitumour activity in patients with MET amplification-driven advanced NSCLC who had previously received chemotherapy or were chemotherapy-naive. Further research is needed to validate these findings.
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