Xtandi (enzalutamide capsule)

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.

P1/2, N=150, Active, not recruiting, ESSA Pharmaceuticals | Recruiting --> Active, not recruiting | Trial completion date: Jan 2026 --> Jan 2025 | Trial primary completion date: Aug 2025 --> Oct 2024

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

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.

P3, N=439, Active, not recruiting, Curium US LLC | Trial completion date: Jun 2029 --> Feb 2029

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

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.

Moreover, enzalutamide-resistant C4-2B MDVR cells display higher HMGA2 levels compared to C4-2B cells, as well as sensitivity to RSL3 ferroptosis inducer, which is partially reversed by ferroptosis inhibitor, ferrostatin-1. Moreover, HMGA2-expressing cells including enzalutamide-resistant cells are susceptible to RSL-3-induced ferroptosis. Thus, ferroptosis sensitivity offers promising insights for the development of targeted therapeutic interventions for aggressive PCa.

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.

P1/2, N=81, Recruiting, Cancer Research UK | N=135 --> 81

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

P2, N=192, Active, not recruiting, MacroGenics | Trial primary completion date: Feb 2025 --> Jul 2024

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

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

P=N/A, N=450, Recruiting, Janssen-Cilag Ltd. | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Dec 2025 --> Jun 2026

P3, N=900, Recruiting, Pfizer

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

P2, N=90, Active, not recruiting, Merus N.V. | Recruiting --> Active, not recruiting

P1/2, N=48, Recruiting, Fred Hutchinson Cancer Center | Not yet recruiting --> Recruiting

P3, N=600, Recruiting, Pfizer | Not yet recruiting --> Recruiting

P2, N=45, Active, not recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Sep 2025 --> Sep 2026 | Trial primary completion date: Sep 2024 --> Sep 2025

Furthermore, MJP6412 demonstrated significant inhibition of tumor growth in a VCaP xenograft model. Collectively, MJP6412 is a promising lead compound for the treatment of prostate cancer, especially enzalutamide-resistant prostate cancer.

Second-generation androgen receptor axis-targeted (ARAT) agents, namely abiraterone acetate (AbA) and enzalutamide (ENZ), are currently used in the management of metastatic castration-resistant PC (mCRPC). In the same subgroup, significant associations of HSD3B1 rs1047303 (CC/CA vs. AA; HR = 3.41; p = 0.025), YBX1 rs12030724 (AT vs. AA; HR = 3.54; p = 0.039) and YBX1 rs10493112 (log-rank test, p = 0.041; CC vs. AA/AC; HR = 3.22; p = 0.053) with overall survival were also observed, which were confirmed by multivariate Cox analyses. Although validation with larger cohorts is required, these findings suggest that SNPs could enhance the prognosis assessment of mCRPC patients, leading to a more personalised treatment.

P1/2, N=39, Not yet recruiting, University of Michigan Rogel Cancer Center

This review and hypothetical case study illustrate the role of oncology nurses and APPs in the administration of talazoparib plus enzalutamide and the management of adverse events to ensure safe and effective use in clinical practice. Oncology nurses and APPs play an important role in the dosing and administration of talazoparib plus enzalutamide and can recognize and manage adverse events in patients with HRR-deficient mCRPC.

P2, N=69, Completed, Medical University of South Carolina | Active, not recruiting --> Completed

P2, N=60, Not yet recruiting, Washington D.C. Veterans Affairs Medical Center

Recent approvals and ongoing investigations of single agents and intensification approaches will keep transforming the mCRPC treatment landscape. Improvement of patient profiling applying recognized genomic, molecular, and clinical predictive and prognostic indicators is fundamental to optimize sequential use of available therapies.