Igermetostat Plus Enzalutamide Delivers Promising rPFS in Post-Abiraterone mCRPC

Igermetostat (XNW5004), a selective EZH2 inhibitor, pairs effectively with enzalutamide in metastatic castration-resistant prostate cancer after prior novel hormone therapy, based on phase 1b/2 results. EZH2 inhibition reverses enzalutamide resistance through epigenetic changes in castration-resistant prostate cancer models. The study endpoints focused on recommended phase 2 dose, safety, and radiographic progression-free survival.
​Eighty-four patients enrolled by September 2025: median age 69 years, average two prior therapies, 83% post-abiraterone, 15.5% visceral metastases, 10.7%prior taxane. Grade 3 or higher treatment-emergent adverse events occurred in 25 percent (treatment-related 17.9 %); serious events in 13.1% (treatment-related 4.%). No dose-limiting toxicities.

Among 53 post-abiraterone patients with 13.2 months median follow-up, median radiographic progression-free survival was not reached (95 percent confidence interval lower bound 10.97 months), 12-month rate 59.8 percent, median overall survival not reached. In 15 with measurable disease, best overall response rate was 26.7 percent including four partial responses. PSA50 response in 31.4 percent of 35 evaluable. At 1200 mg twice daily (the highest dose tested) with 11.9 months follow-up: median radiographic progression-free survival not reached (lower bound 11.01 months), 12-month rate 70.8 percent.
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Source.

Clinical trial.