Abstract 302P
Background
SYHA1813 is a novel small-molecule vascular endothelial growth factor receptors (VEGFRs)/ colony-stimulating factor 1 receptor (CSF1R) inhibitor, exerting synergistic antitumor effects through inhibiting angiogenesis and modulating macrophage polarity in preclinical models. We report preliminary results from a phase Ⅰ, DE study of SYHA1813 in pts with recurrent or advanced solid tumors including HGG.
Methods
Adult pts with recurrent HGG or advanced solid tumors that have progressed on/been intolerant to the standard therapy were enrolled. An accelerated titration design was utilized at 5 mg and 15 mg once daily (QD), followed by a standard 3 + 3 scheme with a starting dose of 30 mg QD. Safety, pharmacokinetics, biomarkers, and preliminary efficacy were evaluated.
Results
Up to date of 15 Feb 2022, 14 eligible pts received SYHA1813 5 mg (n = 1), 15 mg (n = 8), and 30 mg (n = 5). The tumor types included WHO grade III or IV gliomas (n = 13) and colorectal cancer (n = 1). The dose-limiting toxicities (DLTs) were grade (G) 4 hypertension (n = 1) and G3 mucositis oral (n =1) at 30 mg. The maximum tolerated dose (MTD) was identified as 15 mg QD, which was chosen as the dose for the expansion cohort. The most frequently reported treatment-related adverse events (TRAEs) were hypertension (42.9%), platelet count decreased (35.7%), sinus bradycardia (35.7%), and G3/4 TRAEs were hypertension (35.7%), platelet count decreased (14.3%), mucositis oral (7.1%). After a single dose, SYHA1813 was absorbed rapidly, with peak plasma concentrations observed for ∼2 hours. The exposure at steady state, as measured by Cmax and AUC, increased with escalating doses. Of 10 measurable pts, 2 gliomas pts experienced partial response; 7 pts had stable disease, one with glioma for > 6 mo; 1 pt developed progressive disease. By multiple-dose administration, placental growth factor (PlGF), and VEGFA were significantly increased (P = .0484 and .0092, respectively), whereas soluble VEGFR2 was significantly reduced (P = .0023).
Conclusions
SYHA1813 showed manageable safety and encouraging antitumor activities at selected dose levels, which warranted further development in pts with recurrent HGG.
Clinical trial identification
ChiCTR2100045380, China.
Editorial acknowledgement
Legal entity responsible for the study
Shanghai Runshi Medical Technology Co., Ltd.
Funding
Shanghai Runshi Medical Technology Co., Ltd.
Disclosure
H. Wang, Y. Su, Y. Yang, J. Qiu: Financial Interests, Institutional, Full or part-time Employment: CSPC Pharmaceutical Group Co., Ltd. All other authors have declared no conflicts of interest.