Xtandi (enzalutamide)

P3, N=49, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: Jun 2026 --> Jun 2027

P1, N=56, Not yet recruiting, Astellas Pharma Global Development Inc.

This study clarifies the clinical relevance of cytoplasmic AR-V7 in circulating tumor cells from men with metastatic castration-resistant prostate cancer. While nuclear-localized AR-V7 predicts extremely poor response, PFS, and overall survival with AR pathway inhibitors, cytoplasmic AR-V7 expands the definition of AR-V7-positive status and identifies patients with equally poor PFS and intermediate response and overall survival outcomes. Assessing both nuclear and cytoplasmic AR-V7 fractions may thus improve risk stratification heterogeneity and could better guide poor-risk ARPI treatment decisions by avoiding ineffective ARPI treatment, helping personalize therapy, and improving outcomes in men with mCRPC.

P1, N=300, Recruiting, Janssen Research & Development, LLC | Trial completion date: Sep 2027 --> May 2028 | Trial primary completion date: Jun 2026 --> Aug 2027

P=N/A, N=1400, Recruiting, Bayer | Trial completion date: Feb 2026 --> May 2026 | Trial primary completion date: Feb 2026 --> May 2026

P1/2, N=123, Recruiting, Novartis Pharmaceuticals | N=73 --> 123

Notably, these compounds also inhibited the growth of several human PCa cell lines and displayed synergistic effects when combined with the standard-of-care antiandrogen enzalutamide. Together, our findings provide evidence that murine tumoroids are versatile preclinical models for studying PCa tumorigenesis and drug sensitivities to develop therapeutic options for PCa patients.

In conclusion, promoting DCN-mediated ferroptosis might be a potential strategy for enhancing the sensitivity of enzalutamide in PCa cells. This study delineates a novel mechanism by which DCN downregulation suppresses ferroptosis and drives enzalutamide resistance in CRPC.

P1, N=42, Completed, University of Chicago | Active, not recruiting --> Completed

C4-2B and 22Rv1 CRPC cell lines were treated with increasing QRC concentrations, with or without enzalutamide (Enz)...Enz cotreatment with QRC did not produce additive effects, consistent with a model in which QRC acts upstream of ligand-driven AR activation and thereby limits the incremental benefit of AR antagonism under these conditions. These data support QRC as an AKT-AR axis modulator in CRPC and provide a target engagement framework beyond simple ROS scavenging.

In summary, this study defines a core epigenetic pathway, showing that increased SMARCA4 activity promotes luminal-to-neuroendocrine transformation by enhancing histone acetylation and chromatin accessibility at the PROX1 locus. Targeting the SMARCA4-PROX1 axis provides a valuable therapeutic strategy for combating enzalutamide resistance and NEPC progression.

Olaparib plus durvalumab demonstrated modest activity in HRR-unselected mCRPC, with clinical benefit enriched in BRCA2-variant disease. Integrated ctDNA and peripheral immune analyses support ongoing efforts to refine molecular and immune selection strategies and to better define mechanisms of benefit and resistance for combination approaches in mCRPC.