SYHA1813, A VEGFR and CSF1R Inhibitor, in Patients With Recurrent High-Grade Gliomas: A Multicenter, Open-Label Phase...

Area of Science:

• Neuro-oncology
• Translational oncology
• Pharmacology

Background:

• Recurrent high-grade gliomas present a significant clinical challenge with limited treatment options.
• Vascular Endothelial Growth Factor Receptor (VEGFR) and Colony-Stimulating Factor 1 Receptor (CSF1R) are key targets in glioma progression.
• SYHA1813 is an investigational dual inhibitor targeting both VEGFR and CSF1R.

Purpose of the Study:

• To evaluate the safety and efficacy of SYHA1813 in patients with recurrent high-grade gliomas.
• To determine the optimal dosing and preliminary anti-tumor activity of SYHA1813.
• To assess the drug's penetration into the cerebrospinal fluid.

Main Methods:

• A Phase I/II clinical trial enrolled 64 patients with histologically confirmed recurrent high-grade gliomas.
• Patients received daily doses of SYHA1813 to assess safety and initial efficacy.
• Pharmacokinetic analysis included drug concentration in cerebrospinal fluid.

Main Results:

• Treatment-related adverse events (TRAEs) occurred in 92.2% of patients; 40.6% experienced Grade 3 or higher TRAEs.
• The overall objective response rate (ORR) was 18.8%, and the disease control rate (DCR) was 51.6%.
• Median progression-free survival (PFS) was 2.8 months, and median overall survival (OS) was 15.1 months. In glioblastoma patients, ORR was 18.4% and median PFS was 4.1 months.

Conclusions:

• SYHA1813 demonstrates encouraging anti-tumor activity in recurrent high-grade gliomas.
• The drug exhibits a manageable safety profile, supporting further investigation.
• SYHA1813 shows particular promise for the treatment of recurrent glioblastoma.