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.

11 days ago

Journal

AR (Androgen receptor)

AR F876L • AR T877A • AR W741C

Xtandi (enzalutamide capsule) • Nubeqa (darolutamide)

14d

Evaluating the efficacy of bipolar androgen therapy in extending metastasis-free survival in patients with M0 castrate-resistant prostate cancer with prostate specific antigen progression but not radiological or clinical progression on darolutamide. (ACTRN12624000582550)

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

14 days ago

Enrollment open

Nubeqa (darolutamide)

16d

Neoadjuvant Darolutamide and Relugolix Combination Preceding Radical Prostatectomy for Prostate Cancer (clinicaltrials.gov)

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

16 days ago

Enrollment open • Metastases

Nubeqa (darolutamide) • Orgovyx (relugolix)

16d

INTREPId (INTermediate Risk Erection PreservatIon Trial) (clinicaltrials.gov)

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

16 days ago

Enrollment closed

Nubeqa (darolutamide) • bicalutamide

17d

WOMBAT: Working Out M0 Bipolar Androgen Therapy (clinicaltrials.gov)

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

17 days ago

Enrollment open

Nubeqa (darolutamide)

18d

HAYATE: A Study to Learn About How Safe Darolutamide is and How Well it Works in Combination With Androgen Deprivation Therapy and Docetaxel in Routine Medical Care for Japanese Men With Low Volume Metastatic Hormone-Sensitive Prostate Cancer (clinicaltrials.gov)

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

18 days ago

New trial • Combination therapy • Metastases

docetaxel • Nubeqa (darolutamide)

18d

Evaluating Treatment Outcomes Using Darolutamide and Androgen Deprivation Therapy in Patients With Metastatic Hormone-Sensitive Prostate Cancer. (clinicaltrials.gov)

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

18 days ago

New P4 trial • Metastases

Nubeqa (darolutamide)

22d

BELBEQA: An Observational Study to Learn More About the Use of Darolutamide as a Part of a Combination Therapy in Belgian Men With Metastatic Hormone-Sensitive Prostate Cancer in Routine Medical Care (clinicaltrials.gov)

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

22 days ago

Trial completion • Combination therapy • Metastases

docetaxel • Nubeqa (darolutamide)

24d

PSA-DEEP02: PSA Biochemical Response as Prognostic Factor in Metastatic Castration-Sensitive Prostate Cancer (clinicaltrials.gov)

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

24 days ago

New trial • Metastases

docetaxel • Xtandi (enzalutamide capsule) • abiraterone acetate • prednisone • Nubeqa (darolutamide) • Erleada (apalutamide)

26d

Optimal timing for initiating androgen receptor signaling inhibitor therapy in patients with nonmetastatic castration-resistant prostate cancer: a multicenter collaborative study. (PubMed, Jpn J Clin Oncol)

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.

26 days ago

Journal • Metastases

ARSI (Arylsulfatase Family Member I)

Xtandi (enzalutamide capsule) • Nubeqa (darolutamide) • Erleada (apalutamide)

26d

Androgen receptor pathway inhibitors and drug-drug interactions in prostate cancer. (PubMed, ESMO Open)

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.

26 days ago

Review • Journal

CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4)

Xtandi (enzalutamide capsule) • abiraterone acetate • Nubeqa (darolutamide) • Erleada (apalutamide)

28d

Physical Function During ARSI Treatment (clinicaltrials.gov)

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

28 days ago

Enrollment open • Metastases

Xtandi (enzalutamide capsule) • abiraterone acetate • Nubeqa (darolutamide) • Erleada (apalutamide)

29d

A Study Using Available Data to Learn to What Extent Patients With Prostate Cancer Who Received Second Generation Androgen Receptor Inhibitors Took Their Medication as Prescribed or Stopped Taking Their Medication Completely (clinicaltrials.gov)

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

29 days ago

Trial completion date • Trial primary completion date • Adherence

Xtandi (enzalutamide capsule) • Nubeqa (darolutamide) • Erleada (apalutamide)

30d

An Observational Study to Learn More About the Safety of Darolutamide in Men With Prostate Cancer in Korea (clinicaltrials.gov)

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

30 days ago

Enrollment open

Nubeqa (darolutamide)

ASCERTAIN: A Study to Investigate the Biological Effects of Saruparib (AZD5305), Darolutamide, and in Combination in Men With Newly Diagnosed Prostate Cancer. (clinicaltrials.gov)

P1, N=120, Recruiting, AstraZeneca | Trial completion date: Feb 2025 --> Nov 2025 | Trial primary completion date: Feb 2025 --> Nov 2025

1 month ago

Trial completion date • Trial primary completion date

Nubeqa (darolutamide) • saruparib (AZD5305)

A Study of JNJ-78278343 in Combination With Either JNJ-63723283 (Cetrelimab), Taxane Chemotherapy, or Androgen Receptor Pathway Inhibitors for Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov)

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

1 month ago

Enrollment change

docetaxel • Xtandi (enzalutamide capsule) • abiraterone acetate • prednisone • Nubeqa (darolutamide) • cabazitaxel • Erleada (apalutamide) • cetrelimab (JNJ-63723283) • JNJ-8343

Neoadjuvant Darolutamide and Relugolix Combination Preceding Radical Prostatectomy for Prostate Cancer (clinicaltrials.gov)

P1, N=30, Not yet recruiting, AdventHealth

1 month ago

New P1 trial • Metastases

Nubeqa (darolutamide) • Orgovyx (relugolix)

COACTION Trial - COmbination Androgen bloCkade in inTermediate to hIgh-risk prOstate caNcer (clinicaltrials.gov)

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

1 month ago

New P4 trial

Nubeqa (darolutamide)

PEACE 7: Study Evaluating the Efficacy and Safety of Darolutamide and Stereotactic Dose Escalated Radiotherapy in Patients With Localized Prostate Cancer and High-risk Features of Relapse (clinicaltrials.gov)

P3, N=700, Not yet recruiting, UNICANCER

1 month ago

New P3 trial

Nubeqa (darolutamide)

2ms

Prospective, multicenter, comparative, randomized placebo-controlled Phase III trial evaluating dAroLutamide Addition to anDrogen Deprivation therapy and radIatioN therapy in newly diagnosed prostate cancer with pelvic lymph nodes metastases. Etude de phase III randomisée multicentrique contrôlée contre placebo évaluant l’ajout du darolutamide à l’hormonothérapie et à la radiothérapie chez des patients atteints d’un cancer de prostate avec des métastases ganglionnaires pelviennes. (clinicaltrialsregister.eu)

P3, N=152, ARTIC - Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie

2 months ago

New P3 trial

Nubeqa (darolutamide)

2ms

SAKK 08/23: Darolutamide in Metastatic Castration-Resistant Prostate Cancer (mCRPC) (clinicaltrials.gov)

P2, N=162, Recruiting, Swiss Group for Clinical Cancer Research | Not yet recruiting --> Recruiting

2 months ago

Enrollment open • Metastases

docetaxel • Nubeqa (darolutamide)

2ms

PEACE6-Unfit: ADT +/- Darolutamide in de Novo Metastatic Prostate Cancer Patients With Vulnerable Functional Ability (PEACE6-Vulnerable) (clinicaltrials.gov)

P3, N=300, Recruiting, UNICANCER | Trial completion date: Sep 2033 --> Sep 2037

2 months ago

Trial completion date • Metastases

docetaxel • Nubeqa (darolutamide)

2ms

ORIC-944-01: Study of ORIC-944 in Patients with Metastatic Prostate Cancer (clinicaltrials.gov)

P1, N=250, Recruiting, ORIC Pharmaceuticals | N=42 --> 250 | Trial completion date: Jun 2024 --> Sep 2026 | Trial primary completion date: May 2023 --> Dec 2024

2 months ago

Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Metastases

abiraterone acetate • Nubeqa (darolutamide) • Erleada (apalutamide) • ORIC-944

2ms

Darolutamide-mediated phospholipid remodeling induces ferroptosis through the SREBP1-FASN axis in prostate cancer. (PubMed, Int J Biol Sci)

Moreover, the synergistic antitumor effect of combination therapy with darolutamide and ferroptosis inducers (FINs) was confirmed in PCa organoids and a mouse xenografts model. Overall, these findings revealed a novel mechanism of darolutamide mediated ferroptosis in PCa, laying the foundation for the combination of darolutamide and FINs as a new therapeutic strategy for PCa patients.

2 months ago

Journal

FASN (Fatty acid synthase)

AR mutation

Nubeqa (darolutamide)

2ms

Targeting the cancer cells and cancer-associated fibroblasts with next-generation FGFR inhibitors in prostate cancer co-culture models. (PubMed, Cancer Med)

CAFs exert a protective effect on cancer cells and should be included in the in vitro models to make them physiologically more relevant in screening and testing of FGFRis. The FRS2αi was the most potent agent in reducing the viability and proliferation of the 3D organotypic co-cultures, mainly by disrupting the contact between CAFs and cancer cell clusters. The next-generation FGFRi, FRS2αi, may be a better alternative treatment option for overcoming ARi treatment resistance in advanced PCa.

2 months ago

Journal

CASP3 (Caspase 3)

Xtandi (enzalutamide capsule) • Nubeqa (darolutamide)

2ms

SAKK 08/23: Darolutamide in Metastatic Castration-Resistant Prostate Cancer (mCRPC) (clinicaltrials.gov)

P2, N=162, Not yet recruiting, Swiss Group for Clinical Cancer Research | Initiation date: Aug 2024 --> Nov 2024

2 months ago

Trial initiation date • Metastases

docetaxel • Nubeqa (darolutamide)

2ms

TRIPLE-SWITCH: Docetaxel to Androgen Receptor Pathway Inhibitors in Metastatic Castration Sensitive Prostate Cancer Without Deep PSA Response (clinicaltrials.gov)

P3, N=830, Not yet recruiting, Canadian Cancer Trials Group

2 months ago

New P3 trial • Metastases

docetaxel • Xtandi (enzalutamide capsule) • abiraterone acetate • Nubeqa (darolutamide) • Erleada (apalutamide)

2ms

PEACE8: Treatment With Darolutamide +/- Radiation Therapy for Patients With a Castration Resistant Cancer and Metastases Detected by Functional Imaging (clinicaltrials.gov)

P3, N=336, Not yet recruiting, UNICANCER | Initiation date: Jul 2024 --> Oct 2024 | Trial primary completion date: Jul 2024 --> Oct 2029

2 months ago

Trial initiation date • Trial primary completion date

Nubeqa (darolutamide)

2ms

Comeback From Long coursE Androgen Deprivation Therapy (ADT) With RElugolix and Darolutamide (CLEARED) (clinicaltrials.gov)

P2, N=33, Not yet recruiting, Atish Choudhury, MD | Trial completion date: Aug 2028 --> Nov 2028 | Initiation date: Aug 2024 --> Nov 2024 | Trial primary completion date: Aug 2028 --> Nov 2028

2 months ago

Trial completion date • Trial initiation date • Trial primary completion date

Nubeqa (darolutamide) • Orgovyx (relugolix)

2ms

WOMBAT: Working Out M0 Bipolar Androgen Therapy (clinicaltrials.gov)

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

2 months ago

New P2 trial

Nubeqa (darolutamide)

2ms

Inhibition of human UDP-glucuronosyltransferase (UGT) enzymes by darolutamide: prediction of in vivo drug-drug interactions. (PubMed, Chem Biol Interact)

In particular, it also potently inhibited SN-38, the active metabolite of irinotecan, glucuronidation in HLMs with an IC50 value of 3.84 ± 0.46 μM. The prediction results showed that darolutamide may increase the risk of DDIs when administered in combination with substrates of UGT1A1, UGT1A7, or UGT2B15. Therefore, the combined administration of darolutamide and drugs metabolized by the above UGTs should be used with caution to avoid the occurrence of potential DDIs.

2 months ago

Preclinical • Journal

UGT1A7 (UDP Glucuronosyltransferase Family 1 Member A7) • UGT2B15 (UDP Glucuronosyltransferase Family 2 Member B15)

UGT1A1*1*1

irinotecan • Nubeqa (darolutamide)

3ms

Darolutamide + Androgen Deprivation Therapy (ADT) in Chinese Men With High Risk, Nonmetastatic Prostate Cancer (clinicaltrials.gov)

P2, N=78, Active, not recruiting, Bayer | Recruiting --> Active, not recruiting

3 months ago

Enrollment closed

Nubeqa (darolutamide)

3ms

Neoadjuvant Therapy of Darolutamide Plus ADT for High Risk Prostate Cancer (clinicaltrials.gov)

P2, N=80, Recruiting, Xijing Hospital

3 months ago

New P2 trial

Nubeqa (darolutamide) • goserelin acetate

3ms

Docosahexaenoic acid enhances the treatment efficacy for castration-resistant prostate cancer by inhibiting autophagy through Atg4B inhibition. (PubMed, Arch Biochem Biophys)

Furthermore, we investigated the effect of DHA on resistance to ARSI by establishing darolutamide-resistant prostate cancer 22Rv1 (22Rv1/Dar) cells, which had developed resistance to darolutamide, a novel ARSI...DHA significantly suppressed Dar-induced autophagy and sensitized 22Rv1/Dar cells by inducing apoptotic cell death through mitochondrial dysfunction. These results suggest that DHA supplementation may improve prostate cancer therapy with ARSI.

3 months ago

Journal

ATG4B (Autophagy Related 4B Cysteine Peptidase)

Nubeqa (darolutamide)

3ms

Neo-DAB: Darolutamide and Abemaciclib in Prostate Cancer (clinicaltrials.gov)

P1/2, N=9, Active, not recruiting, Praful Ravi, MB BCHir, MRCP | N=93 --> 9

3 months ago

Enrollment change

Verzenio (abemaciclib) • Eligard (leuprolide acetate) • Nubeqa (darolutamide) • goserelin acetate • Firmagon (degarelix)

3ms

Androgen Receptor Signaling and Prostate-Specific Membrane Antigen Expression (clinicaltrials.gov)

P1, N=15, Recruiting, Beth Israel Deaconess Medical Center | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: Sep 2024 --> Sep 2025

3 months ago

Trial completion date • Trial primary completion date

Xtandi (enzalutamide capsule) • Nubeqa (darolutamide) • Erleada (apalutamide)

3ms

Physical Function During ARSI Treatment (clinicaltrials.gov)

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

3 months ago

Enrollment closed • Metastases

Xtandi (enzalutamide capsule) • abiraterone acetate • Nubeqa (darolutamide) • Erleada (apalutamide)

3ms

ARACOG: Androgen Receptor Directed Therapy on Cognitive Function in Patients Treated With Darolutamide or Enzalutamide (clinicaltrials.gov)

P2, N=132, Recruiting, Alliance Foundation Trials, LLC. | Trial completion date: Aug 2024 --> Aug 2026 | Trial primary completion date: Aug 2024 --> Aug 2025

3 months ago

Trial completion date • Trial primary completion date

Xtandi (enzalutamide capsule) • Nubeqa (darolutamide)

3ms

Assessments of prostate cancer cell functions highlight differences between a pan-PI3K/mTOR inhibitor, gedatolisib, and single-node inhibitors of the PI3K/AKT/mTOR pathway. (PubMed, Mol Oncol)

Using a combination of functional and metabolic assays, we evaluated a panel of PC cell lines with different PTEN/PIK3CA status for their sensitivity to multi-node PAM inhibitors (PI3K/mTOR: gedatolisib, samotolisib) and single-node PAM inhibitors (PI3Kα: alpelisib; AKT: capivasertib; mTOR: everolimus). Gedatolisib, as a single agent and in combination with other therapies, reported promising preliminary efficacy and safety in various solid tumor types. Gedatolisib is currently being evaluated in a Phase 1/2 clinical trial in combination with darolutamide in patients with mCRPC previously treated with an AR inhibitor, and in a Phase 3 clinical trial in combination with palbociclib and fulvestrant in patients with HR+/HER2- advanced breast cancer.

3 months ago

Journal

HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • AR (Androgen receptor)

Ibrance (palbociclib) • everolimus • Piqray (alpelisib) • fulvestrant • Truqap (capivasertib) • gedatolisib (PF-05212384) • Nubeqa (darolutamide) • samotolisib (LY3023414)

3ms

P=N/A, N=100, Active, not recruiting, Bayer | Not yet recruiting --> Active, not recruiting

3 months ago

Enrollment closed • Combination therapy • Metastases

docetaxel • Nubeqa (darolutamide)

4ms

Neo-DAB: Darolutamide and Abemaciclib in Prostate Cancer (clinicaltrials.gov)

P1/2, N=93, Active, not recruiting, Praful Ravi, MB BCHir, MRCP | Trial primary completion date: Jul 2024 --> Jul 2025

4 months ago

Trial primary completion date

Verzenio (abemaciclib) • Eligard (leuprolide acetate) • Nubeqa (darolutamide) • goserelin acetate • Firmagon (degarelix)