Firmagon (degarelix) / Astellas, Ferring - LARVOL DELTA

Neoadjuvant Antiandrogen Therapy With or Without MEK or SRC Inhibition for Unfavorable-risk Prostate Cancer: A Phase 2 Randomized Clinical Trial. (PubMed, Eur Urol Oncol) - "Neoadjuvant SRC or MEK inhibition does not appear to mitigate the EMT response to ADT or influence clinical or pathological outcomes."

Clinical • Journal • P2 data • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • CDH2 • MAP2K1 • MAP2K2 • VIM

VPAC antagonism as potential therapeutic for prostate cancer (AACR 2026) - "Enzalutamide upregulated VPAC1 on both M1/M2-like BMDM...Furthermore, degarelix improved the survival of syngeneic TrampC1 tumor (harboring both adenocarcinoma and neuroendocrine phenotypes)-bearing mice, particularly in VPAC1-KO mice, compared to VIP or VPAC2-KO and WT controls, with corresponding benefits in prostate tumor growth control... VPAC1 is an androgen-regulated macrophage checkpoint. VPAC inhibition with ANT308 leads to anti-tumor phagocytosis and enhances ADT-mediated control of prostate tumors in both adenocarcinoma and mixed adeno-neuroendocrine diseases. Further mechanistic investigation is needed to elucidate the intrinsic versus extrinsic role of VIP/VPAC at those stages, informing the design of clinical trials for ANT308 in PC patients."

Genito-urinary Cancer • Neuroendocrine Carcinoma • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • AR • IL12A • MYC • SYP

Enteric and Sympathetic Nervous System Pathways Mediate Early Life Stress Effects on Gut Motility and Pain: Mechanistic Findings with Human Correlation. (PubMed, Gastroenterology) - "These results identify ELS-driven changes in enteric, sensory, and sympathetic pathways as contributors to DGBI risk and offer insight into potential therapeutic targets."

Journal • CNS Disorders • Gastrointestinal Disorder • Immunology • Pain • Pediatrics

Androgen-driven sexual dimorphism reshapes immune crosstalk and limits immunotherapy response in PDAC (AACR 2026) - "Androgen blockade (ARB) with degarelix restored male responsiveness to VPAC inhibition, highlighting androgen-driven resistance in male against VPAC blockade. Combined AR blockade, anti-PD-1, VPAC antagonism, and taxotere markedly extended survival in WT male mice bearing orthotopic MT5 PDAC (MST 54 vs. 18 days for untreated control).These findings show that VPAC signaling restrains TNF-α– and MIF-dependent immune crosstalk and limits phagocytic PDAC clearance. These data also reveal androgen-suppressed phagocytosis as a driver of sexual dimorphism in response to VPAC antagonism and suggest translatable approaches for PDAC treatment."

IO biomarker • Oncology • Pancreatic Ductal Adenocarcinoma • CD4 • CD8 • CSF1R • GZMK • ITGB1 • TNFA

Development of novel syngeneic mouse models of mHSPC and mCRPC for evaluation of radiopharmaceuticals on the immune tumor microenvironment (TME) (AACR 2026) - "In vivo, we conducted biodistribution studies with 177Lu-PSMA-617 in mice bearing bilateral subcutaneous MyC-CaP and MyC-CaPPSMA+ tumors. 100% of MyC-CaPPSMA+ tumors treated with degarelix regressed for 20 days before rebounding.Conclusion Here we reveal translationally relevant models of mHSPC and mCRPC for mechanistic investigations of α- and β-emitting RPTs. Leveraging these tools, we aim to study DNA damage and immune responses to generate foundational data to guide the development of combination therapies to improve outcomes of RPT for patients with mHSPC and mCRPC."

Preclinical • Tumor microenvironment • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • FOLH1 • HER-2

Research Status of Androgen Deprivation Therapy Monotherapy and Combination Therapy for Prostate Cancer: A Scoping Review. (PubMed, Cancer Manag Res) - "There were 52, 67, ten, and 16 studies evaluating leuprorelin, goserelin, triptorelin, and degarelix, respectively. Although numerous studies have evaluated the efficacy of ADT drugs for the treatment of PC, there is still a paucity of high-quality research across multiple domains. Furthermore, there is a relative lack of in-depth research involving Chinese patients."

Journal • Monotherapy • Review • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

CAMO959A12103: A clinical trial to learn about the effects of AMO959 given with AAA617 and an androgen receptor pathway inhibitor (ARPI) in adults with PSMA-positive prostate cancer that has spread to other parts of the body.athway inhibitor (ARPI) in adults with PSMA-positive prostate cancer that has spread to other parts of the body. (clinicaltrialsregister.eu) - P1/2 | N=61 | Not yet recruiting | Sponsor: Novartis Pharma AG

New P1/2 trial • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Supraphysiologic Testosterone Priming Induces Darolutamide Extended Response (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Not yet recruiting ➔ Recruiting

Enrollment open • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Assessing Efficacy of Neoadjuvant ADT in Localized High-Risk Prostate Cancer Patients Utilizing 18F-Flotufolastat PSMA PET/CT (clinicaltrials.gov) - P2 | N=50 | Not yet recruiting | Sponsor: Baptist Health South Florida

New P2 trial • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Androgen deprivation, androgen receptor-targeted vaccination, and nivolumab in patients with high-risk localized prostate cancer. (PubMed, J Immunother Cancer) - P1/2 | "In this first stage of a pilot study that awaits confirmation with larger numbers of patients, our results suggest that vaccination targeting AR given prior to androgen deprivation therapy might improve outcome for patients with high-risk prostate cancer. Contrary to our initial hypothesis, this was not improved with the addition of PD-1 blockade, possibly due to the activation of regulatory CD4+T cells."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • CD4

EORTC-1532: ODM-201 vs Androgen Deprivation Therapy in Hormone naïve Prostate Cancer (clinicaltrials.gov) - P2 | N=250 | Recruiting | Sponsor: European Organisation for Research and Treatment of Cancer - EORTC | Not yet recruiting ➔ Recruiting | Trial completion date: Jul 2021 ➔ May 2022 | Trial primary completion date: Mar 2020 ➔ Dec 2020

Enrollment open • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Neo-DAB: Darolutamide and Abemaciclib in Prostate Cancer (clinicaltrials.gov) - P1 | N=9 | Active, not recruiting | Sponsor: Praful Ravi, MB BCHir, MRCP | Phase classification: P1/2 ➔ P1

Phase classification • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

EORTC-1532: ODM-201 vs Androgen Deprivation Therapy in Hormone naïve Prostate Cancer (clinicaltrials.gov) - P2 | N=61 | Active, not recruiting | Sponsor: European Organisation for Research and Treatment of Cancer - EORTC | Trial primary completion date: Dec 2022 ➔ Dec 2023

Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

EORTC-1532: ODM-201 vs Androgen Deprivation Therapy in Hormone naïve Prostate Cancer (clinicaltrials.gov) - P2 | N=61 | Active, not recruiting | Sponsor: European Organisation for Research and Treatment of Cancer - EORTC | Trial completion date: May 2024 ➔ Dec 2036

Trial completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

EORTC-1532: ODM-201 vs Androgen Deprivation Therapy in Hormone naïve Prostate Cancer (clinicaltrials.gov) - P2 | N=250 | Not yet recruiting | Sponsor: European Organisation for Research and Treatment of Cancer - EORTC

New P2 trial • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

EORTC-1532: ODM-201 vs Androgen Deprivation Therapy in Hormone naïve Prostate Cancer (clinicaltrials.gov) - P2 | N=61 | Active, not recruiting | Sponsor: European Organisation for Research and Treatment of Cancer - EORTC | Unknown status ➔ Active, not recruiting | N=250 ➔ 61 | Trial completion date: May 2022 ➔ May 2024 | Trial primary completion date: Dec 2020 ➔ Dec 2022

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

NeoAdjuvant Theranostic Lutetium Study: The Nautilus Trial (clinicaltrials.gov) - P1/2 | N=6 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | N=36 ➔ 6 | Recruiting ➔ Active, not recruiting

Enrollment change • Enrollment closed • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • CTCs • FOLH1

Disproportionality analysis of adverse events associated with degarelix: a real-world study from the FDA Adverse Event Reporting System (FAERS) database. (PubMed, Clin Transl Oncol) - "Our findings not only validate the established safety data for degarelix but also reveal potential new risks, necessitating continued post-marketing vigilance to guide its safer clinical application."

Adverse events • Journal • Real-world evidence • Cardiovascular • Congestive Heart Failure • Genito-urinary Cancer • Heart Failure • Interstitial Lung Disease • Musculoskeletal Diseases • Oncology • Orthopedics • Prostate Cancer • Pulmonary Disease • Respiratory Diseases • Solid Tumor

Prevalence of major adverse cardiac events in men with prostate cancer receiving androgen deprivation therapy in real-world clinical practice. (ASCO-GU 2026) - "Reporting was carried out for the entire group, men who initiated GnRH agonists (eg, leuprolide) or antagonists (eg, degarelix, relugolix), and men who started ADT before or after relugolix approval (January 2021). In practice, MACE prevalence remained low after initiating ADT. Although differences in baseline characteristics remain, MACE rates were numerically lower in men receiving GnRH antagonists. Use of GnRH antagonists increased following relugolix approval and coincided with a greater awareness of CV risk factors, potentially leading to a decline in MACE rates."

Adverse events • Clinical • Real-world • Real-world evidence • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

PEGASUS: Trial Comparing Irradiation Plus Long Term Adjuvant Androgen Deprivation With GnRH Antagonist Versus GnRH Agonist Plus Flare Protection in Patients With Very High Risk Localized or Locally Advanced Prostate Cancer (clinicaltrials.gov) - P3 | N=885 | Recruiting | Sponsor: European Organisation for Research and Treatment of Cancer - EORTC | Not yet recruiting ➔ Recruiting | Initiation date: Apr 2017 ➔ Sep 2017

Enrollment open • Trial initiation date • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

PEGASUS: Trial Comparing Irradiation Plus Long Term Adjuvant Androgen Deprivation With GnRH Antagonist Versus GnRH Agonist Plus Flare Protection in Patients With Very High Risk Localized or Locally Advanced Prostate Cancer (clinicaltrials.gov) - P3 | N=885 | Not yet recruiting | Sponsor: European Organisation for Research and Treatment of Cancer - EORTC | Initiation date: Oct 2016 ➔ Apr 2017

Trial initiation date • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

PEGASUS: Trial Comparing Irradiation Plus Long Term Adjuvant Androgen Deprivation With GnRH Antagonist Versus GnRH Agonist Plus Flare Protection in Patients With Very High Risk Localized or Locally Advanced Prostate Cancer (clinicaltrials.gov) - P3 | N=885 | Not yet recruiting | Sponsor: European Organisation for Research and Treatment of Cancer - EORTC

New P3 trial • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

PEGASUS: Trial Comparing Irradiation Plus Long Term Adjuvant Androgen Deprivation With GnRH Antagonist Versus GnRH Agonist Plus Flare Protection in Patients With Very High Risk Localized or Locally Advanced Prostate Cancer (clinicaltrials.gov) - P3 | N=885 | Active, not recruiting | Sponsor: European Organisation for Research and Treatment of Cancer - EORTC | Trial completion date: Jun 2024 ➔ Jun 2026 | Trial primary completion date: Jun 2024 ➔ Nov 2023

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

PEGASUS: Trial Comparing Irradiation Plus Long Term Adjuvant Androgen Deprivation With GnRH Antagonist Versus GnRH Agonist Plus Flare Protection in Patients With Very High Risk Localized or Locally Advanced Prostate Cancer (clinicaltrials.gov) - P3 | N=885 | Active, not recruiting | Sponsor: European Organisation for Research and Treatment of Cancer - EORTC | Recruiting ➔ Active, not recruiting

Enrollment closed • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Effects of a GnRH antagonist on antral follicular development and ovarian hemodynamics in cycling ewes. (PubMed, J Reprod Dev) - "Compared with controls, LD ewes had higher (P < 0.05) ovarian artery pulsatility index (PI; D16-17) and resistive index (RI; D17), but lower flow-propagation velocity (FPV; D17), whereas HD ewes exhibited higher PI (D15) and RI (D17), along with lower FPV (D8 and D15) and end-diastolic velocity (D17). Firmagon® treatment was associated with a reduced number of large antral follicles and alterations in ovarian blood perfusion."

Journal