Xtandi (enzalutamide)

P1, N=56, Recruiting, Alessa Therapeutics Inc. | N=20 --> 56 | Trial completion date: Aug 2025 --> Aug 2028 | Trial primary completion date: Jun 2025 --> Jun 2028

Using Bayesian evidence synthesis with prespecified borrowing levels, the Japanese subgroup results were compatible in direction and magnitude with the overall TALAPRO-2 effect. These findings reduce uncertainty around local extrapolation; a dedicated randomized study would be required to establish efficacy independently in Japanese patients.

P2, N=7, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | N=420 --> 7

P2, N=100, Recruiting, Hoffmann-La Roche | Not yet recruiting --> Recruiting

EPHA3 knockout reduces cell proliferation and increases sensitivity to the androgen receptor inhibitor enzalutamide and the YAP1-TEAD inhibitor CA3 in vitro...Bioinformatics analysis further indicates that high YAP1 and EPHA3 correlate with developmental and EMT-related gene signatures. These results demonstrate that the YAP1-EPHA3 axis is a key mediator of cell survival, plasticity, and tumor progression, and may serve as a promising cancer drug target.

P2, N=50, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial primary completion date: Jan 2026 --> Jan 2027

Herein, it is described the case of a 70-year-old man affected by metastatic SCACP, treated with three different sequential therapy lines: carboplatin plus paclitaxel, epirubicin, and an off-label protocol with enzalutamide, achieving 41 months overall survival. Interestingly, SCACP demonstrated to be responsive to enzalutamide treatment, even though the patient precociously stopped the treatment due to severe toxicity. This case represents the first evidence of hormonotherapy administration in a SCACP patient, possibly providing the base for a new therapeutic opportunity for this rare malignancy.

In prostate cancer, MECOM was exclusively overexpressed in both CRPC and enzalutamide-resistant CRPC and interacted with AR in the nucleus...These insights reveal the crucial role of EVI1 in regulating cell survival within the context of an AR-reprogrammed chromatin landscape. More importantly, the findings suggest that MECOM overexpression may be another biomarker that could significantly broaden the use of PARP inhibitors beyond those with HRR gene mutations.

In vitro, enzalutamide-resistant prostate cancer cell lines exhibit heightened glycolysis, and 2-DG inhibition reverses this effect, restoring drug sensitivity. CLN6 knockdown reduces glycolytic activity and cell proliferation. The GLY score offers robust prognostic value, and CLN6 represents a promising therapeutic target for precision medicine in lethal prostate cancer.

PEAK1 plays an oncogenic role in prostate cancer by promoting cell metastasis, reducing docetaxel and enzalutamide sensitivity, and mediating "M2" polarization of macrophages by activating the HIF-1α/STAT3/NF-κB pathway.

Treatment with second-generation androgen receptor (AR) inhibitors, such as enzalutamide, can trigger lineage plasticity, promoting the transdifferentiation of PCa cells into an AR-independent, poorly differentiated neuroendocrine phenotype (NEPC)...Conclusions. These findings establish HOC as a multifaceted therapeutic entity capable of disrupting key NEPC oncogenic networks, highlighting its potential as a novel lead intervention for aggressive NEPC.

P3, N=900, Recruiting, Pfizer | Trial primary completion date: Jul 2026 --> Dec 2026