P1, N=8, Active, not recruiting, Roswell Park Cancer Institute | Recruiting --> Active, not recruiting | N=18 --> 8 | Trial completion date: Jan 2025 --> Mar 2026

Introduction: TALAPRO-2 (NCT03395197) demonstrated that first-line talazoparib + enzalutamide significantly improved radiographic progression-free survival versus placebo + enzalutamide for patients with metastatic castration-resistant prostate cancer (mCRPC). These results are supportive of the ability of F1LCDx to sensitively detect alterations in HRR genes, and the likely overall modest impact of CHiP in calling HRR gene alteration status in this study. These results support the complementary benefits of ctDNA testing to tumor tissue testing in assessing current disease alteration status, particularly AR.

P1, N=63, Completed, Bayer | Active, not recruiting --> Completed

We previously developed and validated a signature reflecting low TSG expression (TSGlow) that was associated with poor outcomes in patients with metastatic hormone-sensitive prostate cancer (mHSPC) treated with androgen deprivation therapy (ADT) ± docetaxel...We found that patients with low expression of two out of three tumor suppressor genes (TP53, RB1, PTEN) had worse clinical outcomes and had aggressive variants of prostate cancer. Measuring the expression of these genes in early-stage prostate cancer could help in finding better treatments for these patients.

P3, N=430, Recruiting, Telix Pharmaceuticals (Innovations) Pty Limited | Not yet recruiting --> Recruiting

P1, N=30, Not yet recruiting, University of Nebraska | Initiation date: Oct 2024 --> Jan 2025

Especially, 4a showed superior efficacy against ARF876L/T877A and ARW741C mutants compared to darolutamide and enzalutamide. Moreover, 4a exhibited favorable pharmacokinetic profiles (F = 66.24%) in vivo and significant tumor growth inhibition in an LNCaP xenograft mouse model upon oral administration. These results highlight the potential of 4a as a promising oral AR antagonist for overcoming drug resistance in PCa.

Talazoparib plus enzalutamide had a generally manageable safety profile in patients with mCRPC within the all-comers and the HRR-deficient populations.

P2, N=69, Recruiting, Australian and New Zealand Urogenital and Prostate Cancer Trials Group | Not yet recruiting --> Recruiting

P1, N=30, Recruiting, AdventHealth | Not yet recruiting --> Recruiting

P2, N=234, Active, not recruiting, Dana-Farber Cancer Institute | Recruiting --> Active, not recruiting

P2, N=69, Recruiting, Australian and New Zealand Urogenital and Prostate Cancer Trials Group | Not yet recruiting --> Recruiting

P2, N=79, Active, not recruiting, Alliance for Clinical Trials in Oncology | Trial primary completion date: Jun 2024 --> Nov 2025

P=N/A, N=100, Not yet recruiting, Bayer

P4, N=80, Not yet recruiting, University of Chicago

MYO6 has pro-tumor and Enz-resistant effects in CRPC, suggesting that targeting MYO6 may be beneficial for ENZ-resistant CRPC therapy through the AR/MYO6/FAK signaling pathway.

P=N/A, N=106, Completed, Bayer | Active, not recruiting --> Completed

P2, N=200, Recruiting, Fudan University

P=N/A, N=152, Not yet recruiting, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

P2, N=60, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2025 --> May 2026 | Trial primary completion date: Oct 2024 --> May 2025

Patients with rapid PSADT are at increased risk of early disease progression, suggesting that immediate treatment may be warranted. In addition, initiating therapy at a PSA level <5.4 ng/ml may be associated with improved patient outcomes in patients with low PSADT.

These interactions, particularly through pathways like CYP2D6 inhibition by abiraterone and CYP3A4 induction by enzalutamide and apalutamide, necessitate a thorough understanding to optimize therapeutic outcomes and minimize adverse effects. This review aims to delineate the efficacy of ARPIs in prostate cancer management and elucidate their interaction with common medications, highlighting the importance of vigilant drug management to optimize patient care.

P2, N=214, Active, not recruiting, Centre hospitalier de l'Université de Montréal (CHUM) | Trial completion date: Sep 2024 --> Dec 2024 | Trial primary completion date: Jul 2024 --> Dec 2024

P=N/A, N=24, Recruiting, UNC Lineberger Comprehensive Cancer Center | Active, not recruiting --> Recruiting

Combination therapy with enzalutamide and JH-RE-06 significantly suppresses cancer growth in a syngeneic murine tumor model over vehicle control or individual treatment groups. These findings suggest that AR inhibition broadly triggers DNA replication stress in hormone-sensitive prostate cancer, thereby exposing a unique vulnerability that can be exploited by a TLS-disrupting adjuvant for targeted therapy.

P=N/A, N=13779, Active, not recruiting, Bayer | Trial completion date: Sep 2024 --> Dec 2024 | Trial primary completion date: Sep 2024 --> Dec 2024

These findings demonstrate that Abi + Chl treatment lowers autophagy levels and suppresses tumors more effectively than Abi alone.

P1/2, N=76, Recruiting, Weill Medical College of Cornell University | Suspended --> Recruiting

P=N/A, N=600, Recruiting, Bayer | Not yet recruiting --> Recruiting

P=N/A, N=120, Recruiting, Duke University | Trial completion date: Oct 2026 --> Apr 2027 | Trial primary completion date: Oct 2026 --> Apr 2027

For FDA-approved second-generation androgen receptor (AR) antagonists, including enzalutamide (ENZ) and abiraterone (AA), patients who initially respond to them eventually develop resistance. ENZ combined with PAP can significantly inhibit 22Rv1 xenograft growth in mice without experiencing castration. Owing to the low toxicity, PAP has potential to offer a new antiandrogen treatment for current ENZ-resistant PCa.

Introduction: TP-2 (NCT03395197) demonstrated statistically significant improvement in rPFS with 1L talazoparib (TALA) + enzalutamide (ENZA) in patients (pts) with mCRPC with and without HRR gene alterations (HRRm; prospectively determined). Broad differential efficacy benefit was evident for TALA+ENZA vs PBO+ENZA across multiple molecular subgroups and was most pronounced for the BRCA1 - PALB2 - BRCA2 axis and CDK12.

Our findings uncovered the critical role of acetate metabolism in NED-mediated CRPC and suggest that ACSS2 inhibitors may represent a novel, low-toxicity strategy when combined with hormone therapy for treating patients with NED-mediated CRPC.

P2, N=474, Not yet recruiting, Alliance for Clinical Trials in Oncology

P1, N=200, Recruiting, Janssen Research & Development, LLC | N=345 --> 200

P2, N=50, Recruiting, Northwestern University | Not yet recruiting --> Recruiting

P3, N=900, Recruiting, Pfizer

P1, N=30, Not yet recruiting, AdventHealth

The trial registration number is NCT02955394. The full trial protocol is available under Study Details at the Clinicaltrials.gov link provided).

P4, N=144, Not yet recruiting, Brazilian Clinical Research Institute

No abstract available

P3, N=700, Not yet recruiting, UNICANCER