A phase 1b/2 study to evaluate the safety and efficacy of igermetostat (XNW5004) in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer.

作者：Yuan Chang, Jian Zhang, Haitao Niu, Jiasheng Bian, Shusuan Jiang, Chaozhao Liang, Yonghong Li, H. Guo, Jinchun Xing, Zimin Shi, Jing Li, H. Chen, Bin Hu, Xiang Li, Jianguo Zhang, Shudong Zhang, Sheng Wang, Xiaoping Zhang, Tianjiao Guo, Dingwei Ye · 发表于：Journal of Clinical Oncology · 年份：2026 · DOI：10.1200/jco.2026.44.7_suppl.169 · 被引用次数：1 · 研究领域：Prostate Cancer Treatment and Research、Chemical Reactions and Isotopes、Epigenetics and DNA Methylation

169 Background: Overexpression of EZH2 is associated with poor prognosis in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). Inhibition of EZH2 has been reported to overcome enzalutamide (E) resistance in CRPC. Igermetostat is a highly selective, small molecule EZH2 inhibitor. Here, we report the safety and efficacy of igermetostat in combination with E in mCRPC pts from a phase 1b/2 study (NCT06702995). Methods: mCRPC pts who had received one novel hormone therapy (NHT) except E and whose disease had progressed on the received NHT per PCWG3 criteria were eligible for this multicenter, phase 1b/2 study in China. In phase1b, 3+3 design was used for dose escalation in 3 dose levels of igermetostat (800, 1200, 1600mg, p.o, BID) + E (160 mg QD) and 2 of them were selected to confirm RP2D. In phase 2, igermetostat 1200mg BID + E were selected for dose expansion. The primary endpoint was RP2D, safety, and radiographic progression-free survival (rPFS). Best overall response (BOR), ≥50% PSA decline from baseline (PSA 50 ), and pharmacokinetics (PK) were also assessed. Results: As of Sep 05, 2025, 84 mCRPC pts were treated with igermetostat at dose levels of 800mg BID (n=3), 1200mg BID (n=65), or 1600mg BID (n=16) in combination with E. Median age was 69 years. The median lines of prior systemic therapy were 2. 83.3% of the pts received abiraterone previously. 15.5 % of the pts had visceral metastasis. 10.7% of the pts had received prior taxane therapy. The...