506MO - A phase I dose-expansion cohort of SYHA1813, a vascular endothelial growth factor receptor (VEGFR) 1-3 /colony-stimulating factor 1 receptor (CSF1R) inhibitor, in patients (pts) with recurrent meningioma

Background

SYHA1813 is a highly potent inhibitor, mainly against VEGFR1-3/CSF1R, and exerts synergistic anti-tumor effects by blocking tumor angiogenesis and modulating tumor microenvironment. Here, we report early findings from pts treated with SYHA1813 in the recurrent meningioma cohort.

Methods

Adult pts (Karnofsky performance status ≥ 60) with recurrent histologically confirmed meningioma not amenable to surgery or radiotherapy were enrolled and treated with 15mg or 20mg SYHA1813 once daily. The primary endpoints were objective response rate (ORR) and the 6-month progression-free survival rate (PFS-6) per Response Assessment in Neuro-Oncology Criteria for meningioma. The secondary endpoints included incidence, type, and severity of adverse events, graded by Common Terminology Criteria for Adverse Events (Version 5.0).

Results

As of Apr. 12, 2023, 11 eligible pts (5 males) with a median age of 50 (range 34-76) were enrolled, including 1 with World Health Organization (WHO) grade I tumor, 6 WHO grade II, and 4 WHO grade III. The median number of prior surgeries were 2 (range 1-4). With a median treatment duration of 1.45 months (range 0.23-6.24), ORR was 45.5% [95% confidence interval (CI) 16.8%–76.6%], with 1 partial response (PR), 2 minor response (MR), 1 unconfirmed PR and 1 unconfirmed MR. Tumor regression in target lesions was observed in 10 out of 11 pts, of which 6 reached ≥ 25% reductions in tumor size. PFS-6 was 75.8% (95% CI 30.5%-93.7%). All pts experienced treatment-emergent adverse events (TEAEs), of which 6 (54.5%) were ≥ grade 3, and all of them were recovered within 7 days. Of these ≥ grade-3 TEAEs, hypertension occurred in ≥ 2 patients. One patient with a complex surgery history developed a serious TEAE, grade-4 intracranial hemorrhage, which was resolved quickly after interventions. No grade-5 TEAEs were reported.

Conclusions

SYHA1813 showed encouraging objective responses with a well-tolerated safety profile in pts with recurrent meningioma.

Clinical trial identification

ChiCTR2100045380.

Editorial acknowledgement

Legal entity responsible for the study

CSPC Pharmaceutical Group Limited.

Funding

CSPC Pharmaceutical Group Limited.

Disclosure

W. Pu, X. Yang, J. Lin, M. Liu: Financial Interests, Institutional, Full or part-time Employment: CSPC Pharmaceutical Group Limited. All other authors have declared no conflicts of interest.