Nubeqa (darolutamide) / Bayer, Orion Corp - LARVOL DELTA

ASCERTAIN: An open-label, randomized, phase 1, window-of-opportunity study to investigate the biological effects of AZD5305 and darolutamide alone or in combination in men with prostate cancer eligible for radical prostatectomy. (ASCO-GU 2024) - P1 | "The Phase 3 PROpel study showed that first-line combination treatment with olaparib and abiraterone significantly improved radiographic progression-free survival (rPFS) over abiraterone alone in pts with metastatic castration-resistant PC (mCRPC) (hazard ratio [HR], 0.66; 95% CI, 0.54 to 0.81; p<0.001). Similarly, the Phase 3 TALAPRO-2 study showed that first-line talazoparib with enzalutamide resulted in statistically significant improvement in rPFS over enzalutamide alone in pts with mCRPC (HR, 0.63; 95% CI, 0.51 to 0.78; p<0.0001)...Enrollment began in September 2023; sites across North America, Europe and Australia will enroll up to 120 patients. Clinical trial information: NCT05938270."

Clinical • P1 data • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • PARP2

ProstACT Global: A phase 3 study of Lutetium (Lu177) rosopatamab tetraxetan plus SoC vs SoC alone in patients with metastatic castration-resistant prostate cancer (SUO 2025) - P3 | "In Part 1, patients are divided into 3 groups (n=10 each) to receive 2 single intravenous injections of 76 mCi each, 14d apart, of 177 Lu-rosopatamab with standard of care (SoC) combinations with abiraterone, enzalutamide, or docetaxel to characterize biodistribution & safety profiles of 177 Lu-rosopatamab + SoC combinations...Eligible patients must have PSMA-expressing mCRPC and have experienced disease progression on a minimum 12w prior therapy on their 1 st ARPI (abiraterone, apalutamide, darolutamide, or enzalutamide) in metastatic castration-sensitive PC, non-metastatic CRPC, or mCRPC settings...This study is sponsored by Telix Pharmaceuticals and is currently enrolling in Part 1. ClinicalTrials.gov ID: NCT06520345 "

Clinical • Metastases • P3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Analysis of quality-adjusted time without symptoms or toxicity (Q-TWiST) in patients with metastatic hormone-sensitive prostate cancer: From the ARASENS trial. (ASCO-GU 2026) - P3 | "Background: Triplet combination of darolutamide (DARO; an androgen receptor inhibitor) with androgen deprivation therapy (ADT), and docetaxel significantly improved overall survival (OS; HR 0.68; 95% CI 0.57–0.80; P<0.001) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) in the ARASENS trial (NCT02799602). In ARASENS, DARO triplet therapy provided an additional 6.3 months of OS without symptoms or toxicity and a Q-TWiST relative gain of 16.0% corresponding to higher overall quality-adjusted survival vs doublet therapy at 53 months. This highlights the benefit of the standard of care ARASENS regimen for patients with mHSPC."

Clinical • Metastases • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

3-weekly docetaxel 75 mg/m2 vs 2-weekly docetaxel 50 mg/m2 in combination with darolutamide + ADT in patients with mHSPC: Subgroup analyses from the randomised phase 3 ARASAFE trial. (ASCO-GU 2026) - P3 | "The benefits of the D50 approach in reducing grade 3-5 AE rate and NAER (primary endpoints) were independent of patients' age and performance status, as well as of surrogate markers of tumor load. The ARASAFE approach (D50) may therefore represent a potential new standard of care for triple therapy across all mHPSC subgroups. Further follow-up is ongoing to determine its efficacy in terms of oncological outcomes."

Clinical • Combination therapy • P3 data • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Prostate Cancer

Real-World Longitudinal Treatment Outcomes for Patients with Metastatic Castration-Sensitive Prostate Cancer in Japan. (PubMed, Adv Ther) - "Compared with ADT alone or ADT + NSAA, ARSI-based treatments showed faster PSA declines and longer treatment durations. While ARSI-based treatments demonstrated similar PSA-lowering effects, differences in treatment continuation likely reflect real-world clinical management influenced by not only PSA response but also adverse events and patient characteristics."

Journal • Real-world evidence • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Efficacy and safety of darolutamide in combination with androgen deprivation therapy and docetaxel in European patients from the phase 3 ARASENS trial. (PubMed, Eur J Cancer) - "In European patients with mHSPC, darolutamide improved overall survival and secondary endpoints including time to mCRPC and time to pain progression. Darolutamide was well tolerated with similar incidence of TEAEs between treatment groups. Efficacy and safety findings in European patients were consistent with the overall ARASENS population."

Journal • P3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Pain • Prostate Cancer • Solid Tumor

Deep and Durable Prostate-specific Antigen Response to Darolutamide with Androgen Deprivation Therapy and Docetaxel, and Association with Clinical Outcomes for Patients with High- or Low-volume Metastatic Hormone-sensitive Prostate Cancer: Analyses of the Randomized Phase 3 ARASENS Study. (PubMed, Eur Urol) - P3 | "Darolutamide + ADT + docetaxel led to deep and durable PSA responses in patients with high- or low-volume mHSPC. Achievement of undetectable PSA (<0.2 ng/ml) was correlated with better clinical outcomes."

Clinical data • Journal • Metastases • P3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Age-related Efficacy and Safety of Darolutamide Plus Androgen-deprivation Therapy and Docetaxel in Patients with Metastatic Hormone-sensitive Prostate Cancer: A Subgroup Analysis of the Phase 3 ARASENS Trial. (PubMed, Eur Urol Oncol) - "In the 219 patients aged ≥75 yr in ARASENS, darolutamide demonstrated improved efficacy versus placebo and favorable safety, consistent with the findings in patients aged <75 yr. Thus, darolutamide and androgen-deprivation therapy with docetaxel can be considered a standard of care triplet therapy for metastatic hormone-sensitive prostate cancer regardless of patients' age."

Journal • P3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

TRIPLE-SWITCH (SWOG/CCTG-PR26): A randomized phase III clinical trial for the addition of docetaxel to androgen receptor pathway inhibitors in patients with metastatic castration sensitive prostate cancer (mCSPC) and suboptimal PSA response (NCT06592924). (ASCO 2025) - P3 | "Arm 1 will continue standard ADT + ARPI (abiraterone acetate with prednisone, apalutamide, enzalutamide or darolutamide). Correlative studies will explore the prognostic and predictive value of circulating tumor DNA (ctDNA) and the association between molecular signatures in primary prostate cancer tissue and clinical outcomes. Enrolment has been initiated in January 2025 and is ongoing."

Clinical • Metastases • P3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

3-weekly docetaxel 75 mg/m2 vs 2-weekly docetaxel 50 mg/m2 in combination with darolutamide + ADT in patients with mHSPC: Results from the randomised phase III ARASAFE trial (ESMO 2025) - P3 | "Table: LBA92 Docetaxel 75 mg/m 2 Q3W, N=129 Docetaxel 50 mg/m 2 Q2W, N=121 Age, median (IQR), years 68.0 (63.0, 74.0) 67.0 (63.0, 73.0) Metastases at primary diagnosis, n (%) 102 (79.7) 108 (89.3) Metastasis pattern at study entry, n (%) - Non-regional lymph node only 1 (0.8) 0 (0.0) - Bone / non-visceral 108 (83.7) 107 (88.4) - Visceral / other 20 (15.5) 14 (11.6) High volume disease, n (%) 108 (83.7) 104 (86.0) Alkaline phosphatase ≥ ULN, n (%) 73 (56.6) 73 (60.3) Serum PSA, median (IQR), ng/ml 12.2 (2.2, 75) 14.7 (3.6, 57.7) Conclusions ARASAFE demonstrates a statistically highly significant and clinically meaningful reduction in the incidence of grade 3-5 AE rate and NAER for the D50 approach, which may be considered a potential new standard of care. Further follow-up is ongoing to determine its efficacy in terms of oncological outcomes."

Clinical • Combination therapy • Late-breaking abstract • P3 data • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer

Darolutamide in Combination With Androgen-Deprivation Therapy in Patients With Metastatic Hormone-Sensitive Prostate Cancer From the Phase III ARANOTE Trial. (PubMed, J Clin Oncol) - "These results confirm the efficacy and tolerability of darolutamide plus ADT in patients with mHSPC, demonstrating clinically and statistically significant improvement in rPFS and a favorable safety profile consistent with prior phase 3 darolutamide trials."

Combination therapy • Journal • Metastases • P3 data • Castration-Resistant Prostate Cancer • Fatigue • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Pain • Prostate Cancer • Solid Tumor

Triple therapy in metastatic hormone-sensitive prostate cancer. (PubMed, Curr Opin Urol) - "Men with de novo high-volume disease benefit most from the triplet, while in cases with metachronous and/or low-volume disease, survival advantage is still disputable. As efficacy of ADT+NHA does not appear to be substantially amplified by combination with D, those men with a more favorable underlying tumor biology might mostly benefit from this doublet, also taking quality-adjusted survival into account."

Journal • Metastases • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

EORTC GUCG 2238 De-escalate: A pragmatic trial to revisit intermittent androgen-deprivation therapy in metastatic hormone-naïve prostate cancer in the era of new AR pathway inhibitors. (ASCO-GU 2024) - P3 | "Clinical Trial Registration Number: NCT05974774 Background: The development of androgen receptor pathway inhibitors (ARPI) - abiraterone acetate, apalutamide, darolutamide and enzalutamide - has profoundly reshaped the management of metastatic hormone naïve prostate cancer (mHNPC)...Patients may have received docetaxel and radiotherapy as part of standard treatment. The PRECIS-2 (Pragmatic-Explanatory Continuum Indicator Summary) will be used to evaluate the study as a pragmatic trial. Clinical trial information: NCT05974774."

Metastases • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Darolutamide Maintenance in Patients With Metastatic Castration-Resistant Prostate Cancer With Nonprogressive Disease After Taxane Treatment (SAKK 08/16). (PubMed, J Clin Oncol) - "SAKK 08/16 met its primary end point, showing that switch maintenance with darolutamide after prior taxane chemotherapy and at least one ARPI resulted in a statistically significant but clinically modest rPFS prolongation with good tolerability. The median OS with darolutamide maintenance appears promising. Should these findings be confirmed in a larger trial, maintenance treatment could be a novel strategy in managing patients with mCRPC, especially those who responded well to prior ARPI."

Journal • Metastases • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A randomized, multicenter, phase II trial of docetaxel or cabazitaxel with or without darolutamide in patients with metastatic castration-resistant prostate cancer (the DAROTAXEL study) (ESMO 2025) - P2 | "Legal entity responsible for the study Erasmus University Medical Center, Rotterdam, the Netherlands. Funding Bayer."

Clinical • Metastases • P2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Efficacy and safety of darolutamide (DARO) in combination with androgen-deprivation therapy (ADT) and docetaxel (DOC) by disease volume and disease risk in the phase 3 ARASENS study. (ASCO-GU 2023) - P3 | "In pts with mHSPC, the benefits of early treatment intensification with DARO + ADT + DOC on OS and key pt-relevant secondary efficacy endpoints vs PBO + ADT + DOC were similar in patients with high- and low-volume as well as high- and low-risk mH+SPC. The favorable safety profile of DARO was reconfirmed in high/low-volume and high/low-risk populations. DARO + ADT + DOC sets a new standard of care for pts with mHSPC."

Clinical • Combination therapy • P3 data • Genito-urinary Cancer • Prostate Cancer

Use of concomitant G-CSF in maintaining efficacious dose and safe delivery of docetaxel in combination with darolutamide in ARASENS: A phase III study. (PubMed, Eur J Cancer) - P3 | "Appropriate docetaxel dose modifications and early G-CSF use allowed almost all patients to receive an efficacious dose of docetaxel in combination with darolutamide and ADT and may prevent neutropenic complications in patients receiving docetaxel."

Journal • P3 data • Febrile Neutropenia • Genito-urinary Cancer • Hematological Disorders • Hormone Sensitive Prostate Cancer • Neutropenia • Oncology • Prostate Cancer • Solid Tumor

Darolutamide in combination with androgen deprivation therapy and docetaxel in patients with metastatic hormone sensitive prostate cancer (mHSPC): Real-World Evidence from the SOGUG-TRIDA Study of the Spanish Oncology Genitourinary Group (SOGUG) (ESMO 2026) - No abstract available

Clinical • Combination therapy • HEOR • Metastases • Real-world • Real-world evidence • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Addition of darolutamide to first line treatment of metastatic castration-resistant prostate cancer (mCRPC): A randomized open label phase II trial (SAKK 08/23). (ASCO-GU 2025) - P2 | "Funded by State secretariat for education, research and information (SERI) Switzerland Clinical Trial Registration Number: NCT06401980 Background: The implementation of androgen-receptor pathway inhibitors (ARPI) +/- docetaxel (doce) in addition to androgen deprivation therapy (ADT) in metastatic hormone sensitive prostate cancer (mHSPC) has limited the therapeutic options in the mCRPC setting...Continuing enzalutamide in addition to doce versus a switch to doce alone after progression on enzalutamide in later line mCRPC has been demonstrated to prolong PFS in a phase 3 trial...Patients will be randomized 1:1 to receive physician's choice standard of care (SOC: doce, cabazitaxel, 177lutetium-PSMA, radium-223 or olaparib) or SOC with daro...The trial will enroll pts in Switzerland and Spain. Accrual to the study is currently ongoing."

Clinical • Metastases • P2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

BRCAAway: A randomized phase 2 trial of abiraterone, olaparib, or abiraterone + olaparib in patients with metastatic castration-resistant prostate cancer (mCRPC) bearing homologous recombination-repair mutations (HRRm). (ASCO-GU 2024) - P2 | "Median age: 67 years (range 42-85); 55 White, 6 Black; prior Docetaxel 26% for mHSPC, Darolutamide/Enzalutamide 3.3% for nmCRPC; disease sites: bone n=44, viscera n=12, lymph node n=31, other n=3; median baseline PSA: 14 ng/ml (range 0.15-4,037 ng/ml). In mCRPC pts with BRCA1/2 or ATM alterations, abiraterone/prednisone + olaparib was well tolerated and resulted in a longer PFS vs either agent alone or sequentially. Clinical trial information: NCT03012321."

Clinical • Metastases • P2 data • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • ATM • BRCA1 • BRCA2 • HRD

The impact of lead-in androgen-deprivation therapy (ADT) on severe neutropenia (grade≥3) caused by docetaxel in patients with metastatic, hormone-sensitive prostate cancer(mHSPC): A Post Hoc Analysis of ARASENS (ESMO 2025) - P3 | "Patients receiving darolutamide or placebo, both combined with ADT and docetaxel, were divided into two groups based on lead-in ADT usage. Conclusions Patients receiving lead-in ADT, especially within 30 days, had a lower incidence of grade>=3 neutropenia in the first cycle than patients not receiving lead-in ADT. This may contribute to improved prevention of grade≥3 neutropenia."

Clinical • Metastases • Retrospective data • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Age-related efficacy and safety of darolutamide plus androgen-deprivation therapy (ADT) and docetaxel in patients with metastatic hormone-sensitive prostate cancer (mHSPC): A subgroup analysis of ARASENS. (ASCO-GU 2025) - P3 | "Pts with mHSPC benefited from DARO + ADT + DOC irrespective of age (<75 y and ≥75 y), with consistent improvements in OS, time to mCRPC, and time to initiation of subsequent therapy. DARO was well tolerated in both age subgroups, with similar incidences of TEAEs vs PBO."

Clinical • Metastases • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Long-Term Safety and Tolerability of Extended Treatment with Darolutamide in Metastatic Hormone-Sensitive Prostate Cancer (mHSPC): Insights from ARASENS Rollover Study (AUA 2025) - P3 | "Source of Funding: Bayer and Orion Pharma. Approximately 45% of pts with mHSPC remained on DARO for ≥4 yrs, demonstrating long-term clinical benefit of this treatment. Most TEAEs occurred in the first 6 mo of treatment, overlapping with the docetaxel treatment period. No long-term safety concerns were identified in pts who entered the ARASENS ROS."

Clinical • Metastases • Cardiovascular • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Hypertension • Oncology • Prostate Cancer • Solid Tumor

Game changing session 6 : Game changer session: Overall Survival With Darolutamide Versus Placebo in Combination With Androgen-deprivation Therapy and Docetaxel by Stratification Factors in the Phase 3 ARASENS Trial (EAU 2022) - No abstract available

Clinical • Combination therapy • P3 data

Doublet Versus Triplet Therapy in High-volume Metastatic Hormone-sensitive Prostate Cancer Patients with Bone Metastases: Results from the ARON-3 Study. (PubMed, Eur Urol Oncol) - "In exploratory subgroup analyses, TTF and OS estimates varied by bone metastatic burden, but formal interaction testing did not show evidence of heterogeneity. These findings require prospective validation."

Journal • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor