A Phase III Study of SYHA1813 for Recurrent or Progressive High-Grade Meningiomas

SYHA1813 vs Investigators' Choice Treatment in Patients With Recurrent or Progressive High-Grade Meningiomas: A Randomized, Controlled, Multicenter, Phase III Study

This is a randomized, controlled, open-label, multicenter, Phase III clinical study designed to compare the efficacy and safety of SYHA1813 versus treatment of investigators' choice in patients with recurrent or progressive high-grade meningioma not amenable to local therapy.

Approximately136 participants with recurrent or progressive high-grade meningioma who have received surgical resection and radiotherapy will be enrolled and randomized 1:1 to receive either SYHA1813 (experimental group) or investigators' choice (control group) treatment. The primary endpoint is progression-free survival (PFS) assessed by blinded Independent Review Committee (BIRC) using the Response Assessment in Neuro-Oncology Working Group (RANO criteria) for meningioma.

Inclusion Criteria:

• 1. Aged >= 18 years.
• 2. Histologically confirmed WHO grade II/III meningioma (WHO CNS 5th) that is progressive or recurrent.
• 3. Individuals must have received surgery and radiation therapy.
• 4. There is at least one measurable intracranial tumor lesion in the baseline period (RANO-meningioma).
• 5. KPS≥60.
• 6. The expected survival time is >=3 months.
• 7. The organ function level and related laboratory indicators must meet requirement.
• 8. Agree to use reliable and effective methods of contraception during the study treatment period and for at least 3 months after the last study treatment.

Exclusion Criteria:

• 1. Individuals who are known to have severe allergic reaction to the study drug or any other ingredients/excipients in the formulation.
• 2. Meets one of the following conditions: patients with brainstem involvement or extracranial metastasis; patients with severe brain herniation or at risk of brain herniation.
• 3. History of other malignant tumors within 3 years or concurrent active malignant tumors.
• 4. The toxic reactions of previous anti-tumor treatments have not yet recovered to ≤ Grade 1.
• 5. Have used potent inhibitors or inducers of CYP3A4, CYP2C19 or CYP1A2 within the 14 days prior to randomization or are still requiring continued use of such agents.
• 6. Individuals currently receiving warfarin or other oral anticoagulants (excluding those who use low-dose anticoagulants to maintain patency of central venous access or prevent deep vein thrombosis).
• 7. Individuals who are unable to undergo enhanced MRI (such as those with pacemakers, metal dentures, claustrophobia, contrast agent allergies, etc.).
• 8. Individuals with evidence or medical history of bleeding tendency within 2 months prior to randomization.
• 9. Individuals with urine protein ≥ 2+, and 24-hour quantitative urine protein ≥ 1.0 g/24 h upon testing.
• 10. History of acquired immunodeficiency syndrome or HIV antibody positivity in the past; Active hepatitis C; Active hepatitis B.
• 11. Individuals with poorly healing wounds or ulcers, or fractures that require treatment or exhibit poor healing.
• 12. Within 14 days prior to randomization, there were severe chronic or active infections (including tuberculosis infections) that required intravenous injection of antibacterial, antifungal or antiviral therapy.
• 13. Individuals with cardiovascular and cerebrovascular diseases of significant clinical significance.
• 14. Have undergone surgery of major vital organs within 28 days prior to randomization (excluding puncture biopsy).
• 15. Individuals with swallowing difficulties or known medication absorption disorders.
• 16. Pregnant or lactating women.
• 17. Any other conditions that may interfere with the participant's adherence to study procedures, compromise the participant's best interests in participating in the study, or affect study results.