Abstract
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).