Congratulations on Vebreltinib's inclusion in the Expert Consensus on Targeted and Immunotherapy for Gliomas (2025 Edition), Facilitating Standardized and Precision-based Diagnosis and Treatment of Gliomas in China

Vebreltinib Enteric Capsules, a MET inhibitor developed by Beijing Pearl Biotechnology Co., Ltd., a wholly-owned subsidiary of Beijing Avistone Biotechnology Co., Ltd. (Avistone), has been included in the Expert Consensus on Targeted and Immunotherapy for Gliomas (2025 Edition), which was published in Chinese Journal of Neurosurgery, Volume 41, Issue 12, December 2025¹.

Image Source: Official Website of Chinese Journal of Neurosurgery

Glioma is the most common type of primary intracranial tumor originating from glial cells. Current treatment modalities mainly include surgery combined with adjuvant radiotherapy and chemotherapy postoperatively; however, most patients are not sensitive to conventional therapies, resulting in an overall poor prognosis^[2-3]. As novel therapeutic approaches, targeted therapy and immunotherapy have been increasingly proven effective in delaying tumor recurrence and improving treatment outcomes. Based on evidence-based medicine while considering clinical feasibility, this Consensus aims to provide a more practical guidance framework for clinical practice. Vebreltinib has been recommended in both the glioma targeted therapy and combination therapy modules of this Consensus¹.

 01  Targeted Therapy for Glioma – MET Fusion-targeted Therapy

Multiple forms of MET aberrations exist in gliomas, including MET gene fusions (PTPRZ1-MET, CLIP2-MET, ST7-MET, etc.), MET exon skipping mutations (exon 7-8 skipping, exon 10 skipping, exon 14 skipping, exon 19 skipping, etc.), MET gene amplification, MET activating point mutations, and MET protein overexpression. All these MET aberrations can potentially lead to the activation of the MET signaling pathway. MET aberrations are associated with poor prognosis in glioma patients, and targeted therapy may confer survival benefits to this patient population⁴.

For the first time, the Chinese Glioma Cooperative Group identified the recurrent PTPRZ1-MET fusion gene and its four distinct fusion variants in WHO grade-malignant progressive gliomas, which has accelerated the development of vebreltinib, a targeted agent against the MET signaling pathway⁵⁻⁶. Results from the phase Ⅱ/Ⅲ clinical trial (the FUGEN study) in patients with MET-aberrant high-grade gliomas demonstrated that, compared with the chemotherapy group (temozolomide dose-dense regimen or cisplatin plus etoposide regimen), the vebreltinib monotherapy group achieved a 48% reduction in the risk of death, with median overall survival (OS) of 6.31 months versus 3.38 months in the two groups, respectively (HR=0.52, P=0.009). In the vebreltinib group, patients with baseline tumor diameter ≤3 cm experienced an increase in OS from 4.2 months to 32.5 months, with a 73% reduction in the risk of death (HR=0.27, P=0.046). This evidence was categorized as Level Ⅰ evidence, derived from a phase Ⅱ/Ⅲ randomized controlled clinical trial. In April 2024, the National Medical Products Administration (NMPA) approved vebreltinib enteric-coated capsules for the treatment of gliomas. An investigator-initiated exploratory clinical study is currently underway (Chinese Clinical Trial Registry, ChiCTR2500096587) to evaluate the safety and efficacy of vebreltinib in the treatment of newly diagnosed glioblastoma (GBM) patients with MET protein overexpression.

Recommendation: Vebreltinib is recommended for adult patients with IDH-mutant WHO grade 4 astrocytoma harboring the PTPRZ1-MET fusion gene who have failed prior therapies, as well as for GBM patients with a history of lower WHO grade glioma (Level Ⅰ evidence). Enhanced detection of MET pathway aberrations, such as the PTPRZ1-MET fusion gene, is recommended. The selection of targeted agents should be guided by molecular biomarker status, and patients should be advised to participate in clinical trials when appropriate.

 02  Combination Therapy – Penetration Therapy

Preclinical studies have demonstrated that inhibition of the c-MET pathway in glioma cells can sensitize tumors to temozolomide (TMZ) and reverse drug resistance⁷. Prolonged treatment with TMZ with or without bevacizumab (BEV) tends to induce secondary upregulation of MET and aberrant activation of the MET pathway. Meanwhile, there is a cross-regulatory effect between the MET and VEGF pathways, and concurrent inhibition of both may exert a synergistic effect⁸⁻⁹. Based on these findings, Beijing Tiantan Hospital affiliated to Capital Medical University spearheaded the establishment of China’s first interdisciplinary clinic dedicated to cutting-edge and innovative therapies for gliomas (the CURE Clinic). It also pioneered the novel “Penetration Therapy” strategy, such as the combination of vebreltinib with the anti-angiogenic agent BEV and/or the chemotherapeutic agent TMZ, for the treatment of recurrent or progressive high-grade gliomas, with the aim of ameliorating and reversing tumor drug resistance. As of the submission date, a total of 239 patients were referred to receive Penetration Therapy via the CURE Clinic. Among them, 122 patients received the therapy and underwent at least one follow-up assessment, and 70 patients had available survival outcomes or a follow-up duration exceeding 6 months. The overall objective response rate (ORR) reached as high as 47.5% (58/122), the clinical benefit rate (CBR) was 88.5% (108/122), and the 6-month progression-free survival rate (PFS) stood at 47.1% (33/70).

 03  About Vebreltinib Enteric Capsules

 Vebreltinib Enteric Capsules was conditionally approved in China in November 2023 for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition factor (MET) exon 14 skipping mutations; it obtained full approval in China in April 2024 for adult patients with IDH-mutant WHO grade 4 astrocytoma harboring the PTPRZ1-MET fusion gene or glioblastoma (GBM) with a history of lower-grade glioma who have failed prior therapies; and it received a further conditional approval in China in June 2025 for the treatment of adult patients with locally advanced or metastatic NSCLC harboring MET amplification.

References

1. 脑胶质瘤靶向和免疫治疗专家共识(2025版).

2. Weller M, Wen PY, Chang SM, et al. Glioma [J]. Nat Rev Dis2024，10(1):33.DOI:10.1038/s41572-024-Primers ,00516-y.

3. Tan AC, Ashley DM, López GY, et al. Management of glio-blastoma: state of the art and future directions [J]. CA Cancer JClin,2020,70(4):299-312. DO: 10.3322/caac.21613.

4. Cheng F, Guo D. MET in glioma:signaling pathways and targeted therapies [J]. J Exp Clin Cancer Res, 2019.38(1).270.DOI:10.1186/s13046-019-1269-x.

5. Bao ZS, Chen HM, Yang MY,et al. RNA-seq of 272 gliomasrevealed a novel,recurrent PTPRZl-MET fusion transcript insecondary glioblastomas[J]. Genome Res, 2014,24(11):1765-1773. DOI:10.1101/gr.165126.113.

6. Hu H, Mu O, Bao Z,et al. Mutational landscape of secondaryglioblastoma guides MET-targeted trial in brain tumor[J]. Cell2018,175(6):1665-1678.e18. Dol: 10.1016/i.cell. 201809.038.

7. Li MY , Yang P , Liu YW , et al. Low c-Met expression levels are prognostic for and predict the benefits of temozolomide chemotherapy in malignant gliomas [J]. Sci Rep, 2016, 6: 21141. DOI: 10.1038/srep21141.

8. Lu KV , Chang JP , Parachoniak CA , et al. VEGF inhibits tumor cell invasion and mesenchymal transition through a MET/VEGFR2 complex [J]. Cancer Cell, 2012, 22(1): 21-35. DOI: 10.1016/j.ccr.2012.05.037.

9. Chen TT , Filvaroff E , Peng J , et al. MET suppresses epithelial VEGFR2 via intracrine VEGF-induced endoplasmic reticulum-associated degradation [J]. EBioMedicine, 2015, 2(5): 406-420. DOI: 10.1016/j.ebiom.2015.03.021
 

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