Outcomes of H3K27M-altered Diffuse Midline Glioma Adult Chinese Patients and Real-World Experience with German-Sourced ONC201 Targeted Therapy: A Multi-center Study in Hong Kong

Abstract INTRODUCTION A novel dopamine-receptor small molecule inhibitor, ONC201, was observed to elicit a treatment response in patients with H3K27M-altered diffuse midline gliomas (DMG). Given restricted access to this therapy, an alternative formulation from Germany (GsONC201) was made available by compassionate means. We describe the treatment outcomes of these patients and our experience with GsONC201. METHODS This was a multicenter retrospective study of adult Chinese patients with histologically confirmed H3K727M-altered DMG. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival, the observed response rate (ORR) at three-months after radiotherapy and GsONC201-associated adverse effects. RESULTS 27 patients, median age of 40 years (range: 31–52), were identified. 52% (14/27) of tumors arose from the thalamus followed by the pons (22%, 6). 85% (23/27) of patients received standard-of-care (SOC) fractionated radiotherapy. 37% (10/27) of patients received GsONC201 of which 80% (8/10) started it as first-line monotherapy after SOC. The mOS of the entire cohort was 17.4 months (IQR: 12.1–30.0). GsONC201 + SOC patients (8) had a mOS of 18.9 months (IQR: 11.3–54.4) compared to 16.0 months (IQR: 12.5–27.6) for SOC-alone patients (13, Pvalue: 0.57). The ORR was 33% (7/21) and 63% of GsONC201 + SOC patients had a treatment response compared to 15% of SOC-alone patients (Pvalue: 0.01). No GsONC201-associated adverse effects were observed. CONCLUSION This is the first real-world study to review the outcomes of first line imipridone-class agent therapy in adult Chinese DMG patients. GsONC201 was well-tolerated, but its effect on OS remains unknown.