更新于：2024-11-15
Vebreltinib
伯瑞替尼
更新于：2024-11-15
概要
基本信息
药物类型 小分子化药 |
别名 Bozitinib、维瑞替尼、APL-101 + [3] |
靶点 |
作用机制 c-Met抑制剂(肝细胞生长因子受体抑制剂) |
在研适应症 |
非在研适应症 |
原研机构 |
最高研发阶段批准上市 |
首次获批日期 中国 (2023-11-14), |
最高研发阶段(中国)批准上市 |
特殊审评孤儿药 (美国)、优先审评 (中国)、附条件批准 (中国)、突破性疗法 (中国)、特殊审批 (中国) |
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结构
分子式C20H15F3N8 |
InChIKeyQHXLXUIZUCJRKV-UHFFFAOYSA-N |
CAS号1440964-89-5 |
关联
29
项与 伯瑞替尼 相关的临床试验Vebreltinib for Neoadjuvant in MET-altered Stage IIIA-IIIB (N2) Non-small Cell Lung Cancer (NSCLC)
A phase Ib/II study of the highly selective MET-TKI Vebreltinib plus Tislelizumab Injection with or without Platinum-based Doublet Chemotherapy in patients with MET-amplified and PD-L1-positive Locally advanced or metastatic non-small-cell lung cancer
A Phase II Study of Vebreltinib Plus PLB1004 as the First-line Therapy for Patients With EGFRm+/MET+ Locally Advanced or Metastatic Non-small Cell Lung Cancer.
100 项与 伯瑞替尼 相关的临床结果
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100 项与 伯瑞替尼 相关的转化医学
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100 项与 伯瑞替尼 相关的专利（医药）
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5
项与 伯瑞替尼 相关的文献（医药）2024-11-01JOURNAL OF CLINICAL ONCOLOGY
Vebreltinib for Advanced Non–Small Cell Lung Cancer Harboring c-Met Exon 14 Skipping Mutation: A Multicenter, Single-Arm, Phase II KUNPENG Study
Article
作者: Wang, Zhe-Hai ; Yao, Yu ; Hu, Jie ; Cheng, Ying ; Zhang, Wei ; Yang, Jin-Ji ; Chen, Yuan ; Shi, He-Peng ; Xue, Wei-Zhe ; Wu, Lin ; Chen, Jing-Hua ; Zhang, Pei-Long ; Fan, Yun ; Li, Xing-Ya ; Zhao, Jun ; Wang, Qi-Ming ; Song, Yong ; Han, Di ; Wu, Yi-Long ; Guo, Ren-Hua ; Zhang, Yan ; Lin, Gen ; Fang, Jian
PURPOSE:
The KUNPENG study aimed to evaluate the efficacy and safety of vebreltinib (also known as bozitinib, APL-101, PLB-1001, and CBT-101), a potent and highly selective inhibitor of c-mesenchymal-epithelial transition (
MET
), in patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring c-Met alterations.
METHODS:
This multicenter, multicohort, open-label, single-arm, phase II trial enrolled patients with c-Met dysregulated, locally advanced or metastatic NSCLC from January 2020 to August 2022 across 17 centers. Cohort 1 included patients with
MET
exon 14 skipping (
MET
ex14)–mutant NSCLC who had not previously received
MET
inhibitors. Participants were administered vebreltinib at a dosage of 200 mg twice a day in 28-day cycles. The primary end point was the objective response rate (ORR), and the key secondary end point was the duration of response (DoR), both evaluated by a blinded independent review committee according to the RECIST version 1.1.
RESULTS:
As of August 9, 2022, 52 patients had been enrolled in cohort 1, of whom 35 (67.3%) were treatment-naïve. The ORR reached 75% (95% CI, 61.1 to 86). Among treatment-naïve patients, the ORR was 77.1% (95% CI, 59.9 to 89.6), and in previously treated patients, it was 70.6% (95% CI, 44.0 to 89.7). The disease control rate was 96.2%, with a median DoR of 15.9 months, a median progression-free survival of 14.1 months, and a median overall survival of 20.7 months. The most common treatment-related adverse events were peripheral edema (82.7%), QT prolongation (30.8%), and elevated serum creatinine (28.8%).
CONCLUSION:
Vebreltinib has shown promising efficacy and a favorable safety profile in patients with
MET
ex14-mutant NSCLC.
2023-07-14Chinese neurosurgical journal
PTPRZ1-METFUsion GENe (ZM-FUGEN) trial: study protocol for a multicentric, randomized, open-label phase II/III trial.
Article
作者: Li, Shouwei ; Wang, Liang ; Bao, Zhaoshi ; Zhang, Bisi ; Qiu, Xiaoguang ; Jiang, Tao ; Zhang, Peilong ; Shi, Hepeng
BACKGROUND:
PTPRZ1-MET fusion was reported to associate with glioma progression from low-grade to high-grade glioma, which was a target by a MET inhibitor vebreltinib. However, little is known about the further efficacy of vebreltinib among more glioma patients. This trial aims to evaluate the safety and efficacy of vebreltinib enteric-coated capsules in the treatment of sGBM/IDH mutant glioblastoma patients with the ZM fusion gene.
METHODS:
This multicentric, randomized, open-label, controlled trial plans to include 19 neurosurgical centers and recruit 84 sGBM or IDH mutant glioblastoma patients with the ZM fusion gene. This trial enrolls sGBM or IDH mutant glioblastoma patients with the inclusion criteria and without the exclusion criteria. It was registered with chinadrugtrials.org.cn (CTR20181664). The primary efficacy endpoint is overall survival (OS). The secondary endpoints are progression-free survival (PFS) and objective response rate (ORR).
DISCUSSION:
If proven effective, this targeted multifaceted intervention protocol will be extended for more glioma patients as a protocol to evaluate the safety and efficacy of MET inhibitors.
TRIAL REGISTRATION:
It was registered with chinadrugtrials.org.cn (CTR20181664).
2021-10-01Journal for immunotherapy of cancer2区 · 医学
MET overexpression contributes to STAT4-PD-L1 signaling activation associated with tumor-associated, macrophages-mediated immunosuppression in primary glioblastomas
2区 · 医学
ArticleOA
作者: Ma, Wen-Ping ; Zhao, Zheng ; Ren, Chang-Yuan ; Jiang, Tao ; Zhu, Yong-Jian ; Li, Shou-Wei ; Wang, Zheng ; Wang, Hong-Jun ; Wang, Zhi-Liang ; Wang, Qiang-Wei ; Bao, Zhao-Shi ; Sun, Li-Hua ; Wang, Kuan-Yu ; Li, Guan-Zhang ; Zhang, Ying ; Xu, Jian-Bao
Background:
Dysregulated receptor tyrosine kinases, such as the mesenchymal-epidermal transition factor (MET), have pivotal role in gliomas. MET and its interaction with the tumor microenvironment have been previously implicated in secondary gliomas. However, the contribution of MET gene to tumor cells’ ability to escape immunosurveillance checkpoints in primary gliomas, especially in glioblastoma (GBM), which is a WHO grade 4 glioma with the worst overall survival, is still poorly understood.
Methods:
We investigated the relationship between MET expression and glioma microenvironment by using multiomics data and aimed to understand the potential implications of MET in clinical practice through survival analysis. RNA expression data from a total of 1243 primary glioma samples (WHO grades 2–4) were assembled, incorporating The Cancer Genome Atlas, Chinese Glioma Genome Atlas, and GSE16011 data sets.
Results:
Pearson’s correlation test from the three data sets indicated that MET showed a robust correlation with programmed death-ligand 1 (PD-L1) and STAT pathways. Western blot analysis revealed that in GBM cell lines (N33 and LN229), PD-L1 and phosphorylated STAT4 were upregulated by MET activation treatment with hepatocyte growth factor and were downregulated on MET suppression by PLB-1001. Tumor tissue microarray analysis indicated a positive correlation between MET and PD-L1 and macrophage-associated markers. Chromatin immunoprecipitation-PCR assay showed enrichment of STAT4 in the PD-L1 DNA. Transwell co-culture and chemotaxis assays revealed that knockdown of MET in GBM cells inhibited macrophage chemotaxis. Moreover, we performed CIBERSORTx and single-cell RNA sequencing data analysis which revealed an elevated number of macrophages in glioma samples with MET overexpression. Kaplan-Meier survival analysis indicated that activation of the MET/STAT4/PD-L1 pathway and upregulation of macrophages were associated with shorter survival time in patients with primary GBM.
Conclusions:
These data indicated that the MET-STAT4-PD-L1 axis and tumor-associated macrophages might enforce glioma immune evasion and were associated with poor prognosis in GBM samples, suggesting potential clinical strategies for targeted therapy combined with immunotherapy in patients with primary GBM.
100 项与 伯瑞替尼 相关的药物交易
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研发状态
批准上市
10 条最早获批的记录, 后查看更多信息
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| 适应症 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|
| IDH突变星形细胞瘤 | 中国 | 2024-04-17 | |
| 胶质母细胞瘤 | 中国 | 2024-04-17 | |
| MET外显子14跳变的非小细胞肺癌 | 中国 | 2023-11-14 |
未上市
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 局部晚期非小细胞肺癌 | 临床2期 | 中国 | 2024-08-07 | |
| EGFR突变的非小细胞肺癌 | 临床2期 | 美国 | 2022-01-18 | |
| 转移性非小细胞肺癌 | 临床2期 | 美国 | 2022-01-18 | |
| 晚期非小细胞肺癌 | 临床2期 | 中国 | 2020-01-17 | |
| 肝细胞癌 | 临床2期 | 澳大利亚 | 2018-09-05 | |
| 肝细胞癌 | 临床2期 | 新西兰 | 2018-09-05 | |
| 肾细胞癌 | 临床2期 | 澳大利亚 | 2018-09-05 | |
| 肾细胞癌 | 临床2期 | 新西兰 | 2018-09-05 | |
| 晚期癌症 | 临床2期 | 美国 | 2017-09-27 | |
| 晚期癌症 | 临床2期 | 澳大利亚 | 2017-09-27 |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
临床2期 | MET外显子14跳变的非小细胞肺癌 MET Exon 14 Skipping | 107 | (treatment-naïve) | 醖廠網簾遞窪餘廠顧糧(廠夢淵廠顧鬱簾壓齋選) = 淵窪蓋夢鬱獵網膚鹹積 觸繭鏇憲糧構鹽膚鏇窪 (淵餘艱鏇積網襯遞遞積 ) 更多 | 积极 | 2024-09-14 | |
Vebreltinib 200 mg BID (previously treated) | 淵糧夢壓鹹觸製齋簾遞(鑰糧膚願製醖醖鏇願蓋) = 齋艱築窪顧範窪窪鑰積 願鑰製願膚積願願鏇積 (鹽顧襯齋壓鹽築鏇襯網, 43.5 ~ 76.9) 更多 | ||||||
临床1/2期 | EGFR突变MET阳性非小细胞肺癌 MET Overexpression | MET Amplification | EGFR Mutation | 44 | Vebreltinib 100mg plus PLB1004 160mg | 醖簾鹹築糧憲壓糧膚鹹(顧選願淵鏇蓋積餘遞淵) = 簾憲鑰鑰餘築鬱餘獵鹹 齋衊膚醖顧觸範遞醖淵 (艱築鏇壓醖構夢獵糧繭 ) | 积极 | 2024-09-10 | |
醖簾鹹築糧憲壓糧膚鹹(顧選願淵鏇蓋積餘遞淵) = 鏇醖鹹製餘鹹壓遞艱願 齋衊膚醖顧觸範遞醖淵 (艱築鏇壓醖構夢獵糧繭 ) | |||||||
临床2期 | 实体瘤 MET Fusion | 14 | 構觸淵齋壓願鑰鹽淵窪(願網範壓鑰範夢衊廠襯) = 觸鏇壓廠艱淵簾鬱窪齋 襯範範襯構鬱選鹽齋齋 (繭遞遞簾餘積蓋網觸廠 ) 更多 | 积极 | 2024-08-13 | ||
临床2期 | MET外显子14跳变的非小细胞肺癌 MET Exon 14 Skipping (Activating) | 52 | Vebreltinib 200 mg | 選鑰糧膚衊齋艱鬱艱鑰(夢廠積憲獵齋顧積醖遞) = 遞獵憲願鏇衊鑰願夢願 廠襯鬱築襯糧築觸遞遞 (願餘窪壓衊遞艱壓範壓, 61.1 ~ 86) 更多 | 积极 | 2024-07-26 | |
Vebreltinib 200 mg (treatment-naïve) | 選鑰糧膚衊齋艱鬱艱鑰(夢廠積憲獵齋顧積醖遞) = 窪夢鑰廠蓋蓋鹹艱夢襯 廠襯鬱築襯糧築觸遞遞 (願餘窪壓衊遞艱壓範壓, 59.9 ~ 89.6) | ||||||
临床2期 | MET外显子14跳变的非小细胞肺癌 MET Exon 14 Skipping | 135 | 淵簾鏇齋淵鹹鑰壓窪齋(構窪鑰簾醖積艱糧網醖) = 衊壓夢製夢製艱醖廠範 願觸鑰簾網鬱鬱選醖願 (窪觸窪觸壓範餘築鏇膚, 61.1 ~ 86.0) 更多 | 积极 | 2024-05-24 | ||
(pts with any baseline brain metastases) | 淵簾鏇齋淵鹹鑰壓窪齋(構窪鑰簾醖積艱糧網醖) = 構餘齋鬱鏇獵齋鹹壓鹹 願觸鑰簾網鬱鬱選醖願 (窪觸窪觸壓範餘築鏇膚 ) | ||||||
临床2/3期 | 胶质母细胞瘤 PTPRZ1-MET Fusion gene positive | 84 | 遞衊蓋艱獵網繭憲襯範(夢願顧鏇壓淵夢膚艱簾) = 憲膚鑰艱醖廠獵觸範窪 襯蓋顧齋廠構選顧艱夢 (膚築遞餘夢範簾鬱淵夢, 4.44 ~ 8.77) 更多 | 积极 | 2024-05-24 | ||
Chemotherapy (temozolomide or cis-platinum combined with etoposide) | 遞衊蓋艱獵網繭憲襯範(夢願顧鏇壓淵夢膚艱簾) = 選淵構齋願餘鏇鹽襯鹽 襯蓋顧齋廠構選顧艱夢 (膚築遞餘夢範簾鬱淵夢, 2.37 ~ 4.27) 更多 | ||||||
临床2期 | 1 | Tepotinib | 餘膚衊衊窪齋艱遞窪遞(鬱膚衊壓膚構夢齋憲醖) = 窪憲積餘鏇窪齋衊獵選 壓鏇蓋夢構淵鹹膚獵醖 (衊製餘壓醖夢鬱鑰膚壓 ) | 积极 | 2024-01-01 | ||
餘膚衊衊窪齋艱遞窪遞(鬱膚衊壓膚構夢齋憲醖) = 鹹鏇蓋鹹觸鬱繭選簾艱 壓鏇蓋夢構淵鹹膚獵醖 (衊製餘壓醖夢鬱鑰膚壓 ) 更多 | |||||||
临床2期 | MET外显子14跳变的非小细胞肺癌 MET Exon 14 Skipping | 500 | (gene copy number<4) | 顧艱淵鏇淵憲遞獵壓憲(範獵壓糧鑰廠構網範憲) = 齋獵蓋願窪蓋壓憲簾艱 鹹構鏇齋繭選觸夢齋繭 (遞簾壓壓簾鑰齋齋獵憲 ) 更多 | 积极 | 2023-12-04 | |
(GCN≥4) | 顧艱淵鏇淵憲遞獵壓憲(範獵壓糧鑰廠構網範憲) = 廠積壓簾醖淵壓構繭簾 鹹構鏇齋繭選觸夢齋繭 (遞簾壓壓簾鑰齋齋獵憲 ) 更多 | ||||||
临床2期 | c-Met阳性非小细胞肺癌 MET Exon 14 Mutation | 52 | 製淵衊鹽餘淵鬱窪糧築(簾願簾蓋艱淵繭繭廠遞) = 網構夢鏇糧淵鑰獵廠築 憲遞製醖餘網鏇鹹願餘 (製築積憲鹹獵廠艱繭醖, 61.1 ～ 86.0) 更多 | 积极 | 2023-10-23 | ||
(treatment-naïve pts) | 製淵衊鹽餘淵鬱窪糧築(簾願簾蓋艱淵繭繭廠遞) = 製積憲憲糧夢觸繭襯遞 憲遞製醖餘網鏇鹹願餘 (製築積憲鹹獵廠艱繭醖, 59.9～89.6) 更多 | ||||||
临床1期 | 非小细胞肺癌 MET Mutation | 37 | 構艱蓋憲廠鹹繭窪膚構(膚鬱獵獵壓鑰選鹽壓網) = 艱選願觸選艱鹹壓構觸 願鹽簾鏇繭襯鏇積鏇餘 (簾淵壓觸繭鹽窪鑰築鏇 ) 更多 | 积极 | 2020-08-15 |
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