Xtandi (enzalutamide)

P3, N=940, Recruiting, Novartis Pharmaceuticals | Trial primary completion date: Feb 2028 --> Sep 2028

P3, N=61, Active, not recruiting, Alliance for Clinical Trials in Oncology | Trial primary completion date: Mar 2026 --> Mar 2027

P1, N=40, Not yet recruiting, Shanghai Changzheng Hospital

P2, N=46, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | N=80 --> 46

P3, N=370, Recruiting, Jiangsu HengRui Medicine Co., Ltd. | Not yet recruiting --> Recruiting

Notably, the combination of NXPH4 knockdown and enzalutamide treatment showed potent synergistic effects, significantly suppressing cell proliferation in vitro and substantially inhibiting tumor growth in vivo. These findings reveal a previously unrecognized mechanism of EnzR and identify the NXPH4-ALDH1L2 complex as a promising therapeutic target for CRPC treatment.

P2, N=7, Completed, Mayo Clinic | Active, not recruiting --> Completed | Trial completion date: Oct 2027 --> Apr 2025 | Trial primary completion date: Oct 2027 --> Apr 2025

Treatment with enzalutamide, an antiandrogen, substantially inhibited patient-derived xenografts growth and demonstrated additive antitumor effects when combined with chemotherapy in AR-positive models...AR expression correlated with poorer overall survival, with statistical significance noted in the full cohort and particularly in male patients. This study suggests that AR may promote metastatic NPC progression via the TTF-1/EGFR signaling pathway and interact with EBV to influence disease behavior, especially in males.

P1/2, N=37, Active, not recruiting, Weill Medical College of Cornell University | Recruiting --> Active, not recruiting | N=76 --> 37

This study developed and validated an LC-MS/MS method for simultaneous quantification of Talazoparib and Enzalutamide in rat plasma using Apalutamide as the internal standard. In pharmacokinetic studies on male Wistar rats, Talazoparib showed a Cmax of 0.88 ng/mL at 3 h and an AUC0-t of 20 ng·h/mL, while Enzalutamide exhibited a Cmax of 76.18 ng/mL at 1 h and an AUC0-t of 1702 ng·h/mL; both had 24 h half-lives. The validated method enables sensitive, rapid, and reliable bioanalysis for preclinical pharmacokinetic evaluation.

Following enzalutamide (ENZ) treatment, GSTA1 expression is inhibited...TNFRSF13B induces c-Fos expression, forming a transcriptional complex with c-Jun, thereby regulating chromogranin A (CHGA) and promoting the neuroendocrine phenotype. Our study suggested that GSTA1 deficiency leads to elevated ROS levels and activation of TNFRSF13B and c-FOS, which subsequently transcriptionally regulate CHGA and ultimately drive neuroendocrine differentiation in PCa.

Additionally, METTL16-mediated m6A modification of EEF1A1 mRNA activates the m6A-IGF2BP1 axis, resulting in increased EEF1A1 protein levels and enhanced resistance to ENZ-induced apoptosis. These findings uncover a novel UFL1-METTL16-EEF1A1 signaling pathway that drives ENZ resistance, suggesting that targeting this cascade may offer a promising therapeutic strategy for overcoming ENZ resistance in prostate cancer.