A phase 2 study of novel MDM2 inhibitor alrizomadlin (APG-115) with or without toripalimab in patients (pts) with advanced adenoid cystic carcinoma (ACC) or other solid tumors.

作者：Ye Guo, Ning Li, Xing Zhang, Meiyu Fang, Shuhang Wang, Yan Yu, Lichuang Men, Hengbang Wang, Yifan Zhai · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.16_suppl.6102 · 被引用次数：5 · 研究领域：Glioma Diagnosis and Treatment、Salivary Gland Tumors Diagnosis and Treatment、Gestational Trophoblastic Disease Studies

6102 Background: Alrizomadlin, an investigational MDM2 inhibitor, has shown a manageable safety profile with preliminary efficacy in liposarcoma (LPS) and ACC and in combination with a PD-1/PD-L1 inhibitor in advanced solid tumors. Methods: This multicenter trial (APG115XC102) assessed alrizomadlin (± toripalimab) in pts with advanced ACC, malignant peripheral nerve sheath tumor (MPNST), LPS, biliary-tract cancer (BTC), or other solid tumors in China. Enrolled pts had an ECOG PS 0-1 and were without central nervous system metastases. Alrizomadlin was administered orally at 50, 100, or 150 mg every other day for 2 weeks, with 1 week off, in repeated 21-day cycles, and combined with toripalimab 240 mg IV for 30 minutes on Day 1 of repeated 21-day cycles until disease progression or unacceptable toxicity. The primary endpoint was RP2D for the combination. ORR was assessed per RECIST v1.1. Results: As of January 5, 2025, 54 pts were enrolled. In the monotherapy arm, 22 pts were treated with alrizomadlin 150 mg; common treatment-related adverse events (TRAEs) included nausea (68.2%), decreased appetite (45.5%), thrombocytopenia (40.9%), white blood cell count decreased (40.9%), neutropenia (36.4%), and hypoalbuminemia (22.7%). Grade ≥ 3 TRAEs included neutropenia (13.6%) and thrombocytopenia (9.1%). No treatment-related serious adverse events (SAEs) were reported. In the combination arm, 32 pts were treated with alrizomadlin at 50 (n = 3), 100 (n = 3), or 150 mg (n = 26). No DLT w...