Ascentage Pharma released Phase II clinical trial data for its MDM2-p53 inhibitor, alrizomadlin (APG-115), at the 2025 ASCO Annual Meeting. The study investigated alrizomadlin as a single agent and in combination with the PD-1 inhibitor toripalimab in patients with advanced adenoid cystic carcinoma (ACC) or other solid tumors. This marks alrizomadlin’s first foray into clinical development in China.
This research holds significant promise for patients with ACC, a rare cancer with limited effective treatment options. Current therapies, such as antiangiogenic tyrosine kinase inhibitors, have limitations and safety concerns. The positive data for alrizomadlin, particularly its potential to target the MDM2-p53 pathway, offers a new therapeutic avenue. Additionally, the combination therapy with toripalimab offers hope for other difficult-to-treat solid tumors like MPNST, BTC, and LPS, where treatment options are also limited.
The Phase II study enrolled 57 patients with various advanced cancers. In the monotherapy arm, alrizomadlin demonstrated a 16.7% objective response rate and a 100% disease control rate in patients with ACC. For the combination therapy, alrizomadlin with toripalimab showed promising activity in MPNST, BTC, and LPS. Two MPNST patients experienced prolonged responses lasting more than 60 and 96 weeks, respectively. While grade 3 or higher treatment-related adverse events were observed, the data suggest a manageable safety profile.
These findings represent a potential advancement in the treatment of ACC and other challenging solid tumors. The demonstrated activity of alrizomadlin, both as a monotherapy and in combination with a PD-1 inhibitor, warrants further investigation. Continued clinical development and larger trials will be crucial to confirm these findings and explore the full potential of alrizomadlin as a novel therapeutic option. The synergistic effects observed with immunotherapy combinations also merit further exploration and could lead to new treatment paradigms in oncology.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
