vebreltinib (APL-101)

P2, N=145, Completed, Beijing Pearl Biotechnology Limited Liability Company | Trial completion date: Dec 2025 --> Jun 2025 | Active, not recruiting --> Completed

While vebreltinib appears clinically advantageous over crizotinib for METex14-mutated NSCLC, the therapeutic benefits did not reach statistical significance in this study. The observed differential response patterns and resistance mechanisms suggest distinct biological behaviors to type Ia and Ib MET TKIs that warrant further investigation. These findings underscore the need for larger prospective studies to validate the potential superiority of vebreltinib and to better characterize the molecular determinants in NSCLC.

Although clinical practice has attempted to combine targeted drugs for MET amplification, such as crizotinib, with first and second-generation ALK-TKIs and observed preliminary efficacy, there is no published research on the combination of third-generation ALK-TKI lorlatinib with new MET inhibitors such as vebreltinib. Our case report first successfully documented the use of third-generation ALK inhibitor (lorlatinib) in combination with novel MET inhibitor (vebreltinib) for the treatment of advanced NSCLC patients with ALK-TKI resistance due to MET amplification, enabling sustained clinical remission. This case highlights the importance of repeat biopsy to identify acquired resistance mechanisms arising from intratumoral heterogeneity in response to targeted therapy, which is critical for making clinical decisions and adjusting treatment plans for patients with NSCLC.

Following oral administration, the predominant radioactive component recovered in faeces was unchanged parent drug. The quantitative metabolic profile confirms significant systemic exposure to the M2 metabolite. These data provide critical insights into the human disposition of vebreltinib, including a MIST assessment, and support its continued clinical development.

Vebreltinib plus an EGFR-TKI demonstrates favorable efficacy and manageable safety in real-world NSCLC patients with MET-driven resistance, with notable intracranial activity. Immunohistochemistry 3 + may serve as a practical predictive biomarker.

P2, N=19, Not yet recruiting, Shanghai Chest Hospital

P=N/A, N=29, Fudan University Shanghai Cancer Center; Fudan University Shanghai Cancer Center

P2, N=37, Zhongshan Hospital, Fudan University; Zhongshan Hospital, Fudan University

In this multicenter, open-label ZM FUsion GENe (FUGEN) trial, patients with previously treated astrocytoma, IDH-mutant, grade 4, or glioblastoma, IDH wild-type, harboring the ZM fusion were randomized in a 1:1 ratio to receive vebreltinib (300 mg orally twice daily) or control treatment (temozolomide or cisplatin plus etoposide) in 28-d cycles. Vebreltinib significantly improved OS in patients with previously treated high-grade glioma harboring the ZM fusion, particularly in the subgroup with IDH-mutant astrocytoma, and the safety profile was manageable. Trial registration: This study was registered with the Chinese Drug Clinical Trial Registry (ChinaDrugTrials.org.cn) under the identifier, CTR20181664 (registration date: 2018 September 19).

P2, N=52, Not yet recruiting, West China Hospital of Sichuan University; West China Hospital of Sichuan University

P2/3, N=84, Active, not recruiting, Beijing Pearl Biotechnology Limited Liability Company | Trial completion date: Dec 2024 --> Dec 2026