Castration-Resistant Prostate Cancer

P1, N=269, Completed, Exelixis | Active, not recruiting --> Completed

The demonstrated delays in definitive deterioration in GHS/QoL, urinary symptoms, and other functioning and symptom scales with talazoparib plus enzalutamide compared with placebo plus enzalutamide in patients with HRR-deficient metastatic castration-resistant prostate cancer provide insight that might inform clinical decisions for these patients.

Talazoparib plus enzalutamide prolonged time to definitive deterioration in GHS/QoL versus placebo plus enzalutamide. Together with clinical efficacy and safety data, these results inform the risk-benefit assessment of talazoparib plus enzalutamide in patients with metastatic castration-resistant prostate cancer in TALAPRO-2.

Three weeks of voluntary wheel running was effective in delaying tumor formation and progression, which coincided with reduced transcription of DNA replication, AR signaling targets and mitochondrial dynamics. We further identified a downregulation in molecular pathways related to angiogenesis that may be responsible for the delayed tumor formation and progression by voluntary wheel running.

P1, N=1274, Active, not recruiting, Exelixis | Recruiting --> Active, not recruiting | Trial completion date: May 2026 --> Jun 2030 | Trial primary completion date: Feb 2026 --> Jun 2030

P=N/A, N=15, Recruiting, Mianyang Central Hospital; Mianyang Central Hospital

P1, N=180, Not yet recruiting, West China Hospital of Sichuan University; Jiangsu Hengrui Pharmaceutical Co., LTD

P1, N=8, Completed, The First Affiliated Hospital of Xiamen University | Recruiting --> Completed | N=20 --> 8 | Trial completion date: Dec 2026 --> Mar 2025 | Trial primary completion date: Dec 2025 --> Mar 2025

This study identified several clinical, biological, and 68Ga-PSMA PET/CT-derived factors associated with early treatment discontinuation. Patients with poor overall health, aggressive or extensive disease, or low PSMA expression are at higher risk of treatment failure.

P=N/A, N=2, Terminated, Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS | N=40 --> 2

Despite demonstrating similar clinical outcomes, cancers from African Americans display distinct tumor biology. Specifically, we observed racial differences in expression of prostate cancer driver gene pathways (including potential clinically actionable pathways of IFN-γ and JAK/STAT) and DNA alterations, including TMPRSS2:ERG gene fusion. Our findings highlight the importance of racial diversity in future genomic profiling and clinical trials efforts.

These findings highlight the scaffold-dependent variability in 3D culture outcomes and emphasize the need for standardized methodologies to ensure consistency and relevance in prostate cancer research. Comparing of Matrigel, GelTrex, and GrowDex in 3D prostate cancer cultureIdentifying scaffold-dependent spheroid formation and gene expression shiftsObserving consistent AR reduction and variable neuroendocrine marker changesHighlighting the need for standard 3D culture methods in cancer studies.

P2, N=474, Recruiting, Alliance for Clinical Trials in Oncology | Not yet recruiting --> Recruiting

P1/2, N=500, Not yet recruiting, CHU de Quebec-Universite Laval | Trial completion date: Jun 2032 --> Mar 2034 | Trial primary completion date: Jun 2028 --> Mar 2033

P1/2, N=90, Recruiting, Portage Biotech | Active, not recruiting --> Recruiting | Trial completion date: Aug 2025 --> Dec 2027 | Trial primary completion date: May 2025 --> Jun 2026

Dynamic changes in the detection rate of histology-specific clones in circulation reflected histology-specific sensitivity to treatment. This dataset serves as an illustration of non-neuroendocrine transdifferentiation and highlights the importance of serial sampling at progression in CRPC for the detection of emergent non-adenocarcinoma histologies with implications for the treatment of lineage plasticity and transdifferentiation in metastatic CRPC.

Additionally, patient dataset analysis revealed that c-Myc plays a significant role in developing ENZ resistance. To summarize, these findings suggest a novel therapeutic strategy for ENZ-resistant prostate cancer.

P1, N=257, Recruiting, Janssen Research & Development, LLC | Trial completion date: Sep 2027 --> May 2028 | Trial primary completion date: Sep 2027 --> May 2028

P2, N=45, Completed, Dana-Farber Cancer Institute | Active, not recruiting --> Completed

P1, N=60, Active, not recruiting, Xencor, Inc. | Recruiting --> Active, not recruiting | N=220 --> 60 | Trial completion date: Dec 2027 --> Jun 2025 | Trial primary completion date: Dec 2027 --> Jun 2025

P2, N=49, Active, not recruiting, University of Michigan Rogel Cancer Center | Trial completion date: Jan 2027 --> Aug 2028

A multivariate analysis, adjusted for age and metastatic dissemination, identified miR-375 expression and LMR to be the independent negative predictors for ARPI therapy failure in CRPC patients. Regarding the HSPC patients, we report the priority finding on the independent negative predictive value of platelets, CRP, and CGA for the therapy failure of the combined ADT and ARPI.

FOR46 demonstrated encouraging preliminary clinical activity with a manageable safety profile. Targeting CD46 elicited an immune priming effect that was associated with clinical outcomes.

In this analysis of patients with early PSMA PET follow-up after ARSi initiation, we observed a PSMA-upregulation by WB-PET imaging in 25% of the patients. Further studies are needed to better understand the potential synergistic and / or additive effects of AR- and PSMA-targeted approaches.

To date, studies have also shown potential clinical benefits. This comprehensive review analyzed the utilization of immunotherapy techniques in the treatment of PCa, assessing their advantages and obstacles, with the aim of providing healthcare professionals and scholars with a comprehensive understanding of the progress in this field.

P1, N=134, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting

P1, N=3, Not yet recruiting, Shanghai Changzheng Hospital

All these data support the notion that BAP1 functions as a tumor suppressor. Integrating BAP1 status with other genomic alterations offers a more comprehensive understanding of disease aggressiveness.

P2, N=420, Not yet recruiting, Novartis Pharmaceuticals

TALAPRO-2 is a notable clinical trial, specifically examining the effectiveness of Talazoparib when used in combination therapies. Current investigations demonstrate a significant improvement in survival outcomes for the patients of mCRPC, making Talazoparib a promising intervention.

P2, N=70, Recruiting, Syncromune, Inc. | Phase classification: P1 --> P2 | N=28 --> 70

P2, N=75, Not yet recruiting, Jina Pharmaceuticals Inc.

Simvastatin altered the expression of several genes associated with DNA repair in castration-resistant and taxane-resistant prostate cancer cells. The combination of poly (ADP-ribose) polymerase inhibitors and drugs that decrease DNA repair gene expression can potentially affect castration-resistant and taxane-resistant prostate cancer growth.

Compound B effectively radiosensitized ATM-deficient CRPC in vitro and in vivo, and impacted replication fork dynamics. Overall, dual targeting of both ATR and DNA-PKcs is necessary to block DDR in ATM-deficient CRPC, and Compound B could be utilized as a novel therapy in combination with irradiation in these patients.

Remarkably, tumors treated with zotatifin become more sensitive to anti-androgen therapy and radiotherapy. Therefore, "translatome therapy" provides additional strategies to treat the deadliest cancers.

Although second-line androgen receptor signaling inhibition treatments such as enzalutamide and abiraterone are available, their effectiveness against CRPC is only transient. Further studies in RB1-silenced CRPC cell lines showed that treatment with a hypoxia-inducible factor-1α inhibitor can restore the sensitivity of Rb-deficient cells to high-dose dihydrotestosterone treatment. In conclusion, our research provides new molecular insights into CRPC tumor cell responses to Hi-T and proposes a new strategy to resensitize Rb-deficient CRPC cells to Hi-T treatment.

Our results revealed gene mutations that are significantly associated with metastatic site selectivity and that frequencies of non-coding mutations at AR chromatin binding sites differ between metastatic sites. Immunotherapeutics are thus far unsuccessful in unselected mCRPC patients. We found a higher TML in liver and visceral metastases compared to bone and lymph node metastases. As immunotherapeutics response is associated with mutational burden, these findings may assist in selecting mCRPC patients for immunotherapy treatment based on organs affected by metastatic disease.

Importantly, combined inhibition of STAT3 and N-glycosylation demonstrated a synergistic effect in reducing tumor viability. Our findings elucidate a novel positive feedback loop involving JAK2/STAT3/GnT-V/PSMA axis, contributing to the malignancy of prostate cancer and providing a foundation for innovative therapeutic strategies targeting this pathway.

The advent of modern molecular profiling methods applied in the clinic, namely, next-generation sequencing and advanced positron emission tomography (PET) imaging, has allowed for the development of biomarker-driven therapeutics including anti-PD-L1 therapy for microsatellite instability-high or tumor mutation burden-high disease, poly(ADP-ribose) polymerase (PARP) inhibitors for patients with DNA damage repair mutations, and lutetium 177 vipivotide tetraxetan (177Lu-PSMA-617) for patients with prostate-specific membrane antigen (PSMA) PET-avid disease...The clinical management of NEPC typically follows the treatment paradigm for small cell lung cancer and increasingly relies on genomic and phenotypic characterization of disease, including loss of tumor suppressors and expression of cell surface markers such as DLL3. Therefore, both genomic subtyping and phenotypic subtyping are important to consider and can guide the clinical management of patients with advanced prostate cancer.

VRK1 serves as a prognostic marker in PCa, regulated by AR signaling. VRK1 depletion inhibited cell proliferation both in vitro and in vivo, while elevated VRK1 upregulated YAP1, promoting cell proliferation and therapeutic resistance.

P1/2, N=40, Enrolling by invitation, Zenith Epigenetics | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026

P1/2, N=277, Completed, Karyopharm Therapeutics Inc | Active, not recruiting --> Completed