446MO - SYHA1813, a vascular endothelial growth factor receptor (VEGFR) 1-3/colony-stimulating factor 1 receptor (CSF1R) inhibitor, in patients with recurrent glioblastoma

Background

Glioblastoma is the most common malignant brain tumor associated with a poor prognosis. There are currently few systemic treatment options that can prolong patient survival after recurrence. SYHA1813 is an oral multi-kinase inhibitor, mainly against VEGFR1-3/CSF1R, and exerts synergistic anti-tumor effects by blocking tumor angiogenesis and modulating tumor microenvironment. Here, we report preliminary results from a recurrent glioblastoma cohort of a phase I study (ChiCTR2100045380).

Methods

Adult patients aged ≥ 18 years with Karnofsky performance status ≥ 60 and histologically confirmed recurrent glioblastoma were enrolled. Patients were treated with five dose levels of SYHA1813 once daily (10, 15, 20, 25 or 30 mg). The aim of the study was to evaluate the safety and preliminary efficacy of SYHA1813. Tumor response was assessed according to the RANO criteria. Adverse events (AEs) were graded by Common Terminology Criteria for Adverse Events (Version 5.0).

Results

As of Mar. 7, 2024, a total of 38 eligible patients with recurrent glioblastoma were enrolled. Thirteen patients (34.2%) had more than once recurrence and 9 patients (23.7%) had been treated with VEGF/VEGFR-targeting therapies. The overall response rate was 18.4% (7 PRs, 95% CI, 7.7-34.3), and the disease control rate was 52.6% (7 PRs + 13 SDs, 95% CI, 35.8-65.0). After a median follow-up of 9.5 months, the median progression-free survival (PFS) was 4.1 months (95% CI 2.3-5.3; 65.8% events), and the median overall survival (OS) was not reached (47.4% events), with OS rate at 12 months was 61.8% (95% CI 42.3-76.4). A total of 17 (44.7%) patients reported grade 3-4 treatment-related adverse events (TRAEs). TRAEs ≥ grade 3 occurred in more than 2 patients were hypertension (28.9%) and decreased platelet count (10.5%). No death was considered by the investigators to be drug related.

Conclusions

SYHA1813 showed encouraging antitumor activity with a manageable safety profile for the treatment of recurrent glioblastoma.

Clinical trial identification

ChiCTR2100045380, Release date: April 14, 2021.

Editorial acknowledgement

Legal entity responsible for the study

CSPC Pharmaceutical Group Limited.

Funding

CSPC Pharmaceutical Group Limited.

Disclosure

X. Yang, F. She, S. Xiang, G. Liu, M. Liu: Financial Interests, Personal, Full or part-time Employment: CSPC Pharmaceutical Group Limited. All other authors have declared no conflicts of interest.