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Published on: October 27, 2014
SYHA1813, A VEGFR and CSF1R Inhibitor, in Patients With Recurrent High-Grade Gliomas: A Multicenter, Open-Label Phase
Zhuang Kang1, Shenglan Li1, Liang Wang2
1Department of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Objective:
Recurrent high-grade gliomas have a poor prognosis and limited therapeutic options. This study aimed to evaluate the safety and efficacy of SYHA1813, a dual inhibitor of VEGFR and CSF1R, in patients with recurrent high-grade gliomas.
Methods:
Eligible patients (aged ≥ 18) with histologically or cytologically confirmed recurrent high-grade gliomas were included. Patients were administered different doses of SYHA1813 daily to assess its safety and initial efficacy.
Results:
Sixty-four individuals with high-grade gliomas were enrolled. Treatment-related adverse events (TRAEs) were reported in 92.2% of the patients, with 40.6% experiencing grade 3 or higher TRAEs. No grade 5 TRAE was reported. The overall objective response rate (ORR) and disease control rate (DCR) were 18.8% (95% confidence interval [CI], 10.1-30.5) and 51.6% (95% CI, 38.7-64.3), respectively. With a median follow-up duration of 9.5 months, the median progression-free survival (PFS) was 2.8 months (95% CI, 2.3-4.2) with PFS-6 of 22.5% (95% CI, 11.8-35.4) and the median OS was 15.1 months (95% CI, 10.2-NE) with OS-12 of 63.3% (95% CI, 49.3-74.4). Among the 38 patients with glioblastoma, the ORR was 18.4% (95% CI, 7.7-34.3), with a DCR of 52.6% (95% CI, 35.8-69.0). The median PFS and OS were 4.1 months (95% CI, 2.3-5.3) and 13.0 months (95% CI, 9.1-NE), respectively. SYHA1813 was detected in cerebrospinal fluid samples and the drug concentration to plasma free drug concentration ratio was 0.30-1.27.
Interpretation:
SYHA1813 exhibits encouraging anti-tumor activity with a manageable safety profile for the treatment of recurrent high-grade gliomas, especially glioblastoma.
Trial Registration:
chictr.org.cn (ChiCTR2100045380).
Insights
SYHA1813, a dual inhibitor of VEGFR and CSF1R, shows promising anti-tumor activity in recurrent high-grade gliomas. This investigational drug demonstrated a manageable safety profile and encouraging efficacy, particularly in glioblastoma patients.
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.
