SYHA1813, A VEGFR and CSF1R Inhibitor, in Patients With Recurrent High‐Grade Gliomas: A Multicenter, Open‐Label Phase I Study

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)