Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Darolutamide (BAY1841788, Nubeqa), Darolutamide (Nubeqa, BAY1841788), Standard Darolutamide, Darolutamide Oral Tablet
Darolutamide · 14 trials · 13 indications
Metastasis-free survival (MFS) is defined as the time interval from randomization to the date of the appearance of metastasis (on next generation imaging) or death (from any cause), whichever occurs first.
The failure-free survival is defined as the time from the date of randomization to clinical (new cancer-related symptoms), biochemical (PSA rising) or radiological (local relapse or new metastases) progression, death, end of 3-year follow-up period or lost to follow-up, whichever occurs first.
rPFS used conventional imaging method (99mTc-phosphonate bone scan, CT/MRI scan). rPFS was defined as the time from the date of randomization to the date of progressive disease in malignant soft tissue lesions, progressive disease in malignant bone lesions, or death due to any cause, whichever occurs first. Malignant soft tissue lesions were assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and malignant bone lesions were assessed by Prostate Cancer Clinical Trials Working Group (PCWG3) criteria.
pRR is defined as the proportion of participants with either condition of pCR or MRD at week 12 or 24 in corresponding arm. Proportion of participants with pCR is defined as the proportion of participants with no residual tumor detected in radical prostatectomy (RP) specimens following 12 or 24 weeks of neoadjuvant treatment of darolutamide and ADT per randomization. Proportion of participants with MRD is defined as the proportion of participants that have residual cancer burden (RCB) ≤0.25 cm\^3 in the RP specimens.
Recurrence Free Survival (RFS), with recurrence event defined as (whichever occurs first): * Biochemical failure defined as per Phoenix criteria (i.e., a rise in PSA by 2 ng/mL or more above the nadir PSA, confirmed by a second PSA measurement) * Clinical, radiographic, or pathological evidence of local, regional, or distant recurrence/metastasis * Initiation of salvage hormonal therapy * Death from any cause.
Time interval from enrollment to PSA progression, clinical progression or death, whichever occurs first. PSA progression is defined as when the PSA demonstrates an increase that is more than 50% of nadir, taking as reference the lowest recorded PSA level since starting androgen deprivation therapy (ADT). Clinical progression is defined as increasing symptomatic bone metastases, radiographic progression per Response Evaluation Criteria In Solid Tumors (RECIST) criteria (v. 1.1) for soft tissue metastases and PCWG3 criteria for bone metastases, or clinical deterioration due to cancer per investigator's opinion.
The proportion of patients with confirmed tumor response of complete response (CR) or partial response (PR) per RECIST 1.1, as assessed by investigators
The proportion of patients with confirmed tumor response of CR or PR per RECIST 1.1, as assessed by an independent review committee
Obtained by comparing whole brain grey matter quantitative voxel-by-voxel maps of cerebral blood flow/ perfusion (mL per 100g tissue per min) of enzalutamide to placebo. Measured in grey matter voxels with arterial spin labeling magnetic resonance imaging (ASL-MRI).
Obtained by comparing whole brain grey matter quantitative voxel-by-voxel maps of cerebral blood flow/ perfusion (mL per 100g tissue per min) of darolutamide to placebo. Measured in grey matter voxels with ASL-MRI.
Obtained by comparing whole brain grey matter quantitative voxel-by-voxel maps of cerebral blood flow/ perfusion (mL per 100g tissue per min) of enzalutamide to darolutamide. Measured in grey matter voxels with ASL-MRI.
| Arm | Type | Description |
|---|---|---|
| Arm A (Standard arm) | OTHER | ADT + conventional fractionated or moderately hypo-fractionated prostate radiotherapy including pelvic nodal radiotherapy |
| Arm B (Experimental arm): | EXPERIMENTAL | ADT + conventional fractionated or moderately hypo-fractionated prostate radiotherapy including pelvic nodal radiotherapy + darolutamide |
| Arm C (Experimental arm): | EXPERIMENTAL | ADT + conventional fractionated or moderately hypo-fractionated pelvic nodal radiotherapy + Prostate SBRT |
| Arm D (Experimental arm): | EXPERIMENTAL | ADT + conventional fractionated or moderately hypo-fractionated pelvic nodal radiotherapy + Prostate SBRT + darolutamide |
| Darolutamide+ADT | EXPERIMENTAL | Participants will receive darolutamide plus ADT twice daily with food for a pre-specified duration of 24 months. |
| Placebo+ADT | PLACEBO_COMPARATOR | Participants will receive Placebo plus ADT twice daily with food for a pre-specified duration of 24 months. |
| Arm A | EXPERIMENTAL | Arm A: ADT + Intensity-Modulated Image-Guided Radiation Therapy + Darolutamide ADT will be associated with LHRH agonists or antagonists for 24 months4. Darolutamide regimen will be of 2 tablets of 300 mg orally twice daily for 24 months. |
| Arm B | PLACEBO_COMPARATOR | Arm B: ADT + Intensity-Modulated Image-Guided Radiation Therapy + Placebo of Darolutamide ADT will be associated with LHRH agonists or antagonists for 24 months4. Darolutamide regimen will be of 2 tablets of 300 mg orally twice daily for 24 months. |
| Darolutamide (BAY1841788) | EXPERIMENTAL | Participants enrolled in the current study will use the dose they were assigned to in the feeder study they come from. |
| Darolutamide | EXPERIMENTAL | Darolutamide 600mg (2 x 300mg tablets) twice daily by mouth for 96 weeks, adherence monitored by participant report. All participants are treated with an LHRHA for 96 weeks from randomisation and external beam radiation therapy started within 8-24 weeks after randomisation. |
| Placebo | PLACEBO_COMPARATOR | Placebo (2 tablets) twice daily by mouth for 96 weeks, adherence monitored by participant report. All participants are treated with an LHRHA for 96 weeks from randomisation and external beam radiation therapy started within 8-24 weeks after randomisation. |
| Darolutamide + docetaxel + ADT | EXPERIMENTAL | Adopting the triple neoadjuvant treatment regimen of Darolutamide + docetaxel + ADT |
| Docetaxel + ADT | ACTIVE_COMPARATOR | Adopting the dual neoadjuvant treatment regimen of docetaxel + ADT |
| Darolutamide + ADT (12 weeks) | EXPERIMENTAL | Participants will receive darolutamide and androgen deprivation therapy (ADT) as neoadjuvant treatment for 12 weeks, followed by radical prostatectomy (RP). |
| Darolutamide + ADT (24 weeks) | EXPERIMENTAL | Participants will receive darolutamide and androgen deprivation therapy (ADT) as neoadjuvant treatment for 24 weeks, followed by radical prostatectomy (RP). |
| Group 1: Radiation Therapy Only | ACTIVE_COMPARATOR | Participants randomized to Group 1 will receive radiation therapy only. |
| Group 2: Radiation Therapy + darolutamide + degarelix | EXPERIMENTAL | Participants randomized to Group 2 will receive radiation therapy only + darolutamide + degarelix. |
| Lead-in phase: Darolutamide treatment | EXPERIMENTAL | Darolutamide treatment arm is single cohort in lead-in phase. |
| Randomized phase: Darolutamide treatment | EXPERIMENTAL | The conduct of the randomized phase is dependent on the results of the lead-in phase. |
| Randomized phase: Enzalutamide treatment | ACTIVE_COMPARATOR | The conduct of the randomized phase is dependent on the results of the lead-in phase. |
| Darolutamide monotherapy | EXPERIMENTAL | Targeted patients: 24 |
| Darolutamide plus Goserelin | EXPERIMENTAL | Targeted patients: 32 |
| Men_EPD | EXPERIMENTAL | Healthy male participants receive drugs in order Enzalutamide, Placebo and Darolutamide. |
| Men_DEP | EXPERIMENTAL | Healthy male participants receive drugs in order Darolutamide, Enzalutamide and Placebo. |
| Men_PDE | EXPERIMENTAL | Healthy male participants receive drugs in order Placebo, Darolutamide and Enzalutamide. |
| Men_DPE | EXPERIMENTAL | Healthy male participants receive drugs in order Darolutamide, Placebo and Enzalutamide. |
| Men_EDP | EXPERIMENTAL | Healthy male participants receive drugs in order Enzalutamide, Darolutamide and Placebo. |
| Men_PED | EXPERIMENTAL | Healthy male participants receive drugs in order Placebo, Enzalutamide and Darolutamide. |
| Name | Type | Description |
|---|---|---|
| Darolutamide | DRUG | Pharmaceutical form: 300 mg tablets Administration route: oral (PO) Posology: 600 mg twice daily (BID) |
| Stereotactic Body RadioTherapy (SBRT) | RADIATION | Following randomization, patients will receive dose escalated intensity modulated radiotherapy (IMRT) using normo-fractionation or moderate hypo-fractionation including whole pelvic nodal radiotherapy (WPRT). At study entry, each investigational site will be asked to choose one regimen (normo-fractionation or moderate hypo-fractionation) which will be applied for all patients included by the investigational site in the study. SBRT, experimental treatment, will be used as a boost in Arms C \& D. The placement of 3 to 4 fiducial markers for stereotactic boost is mandatory. SBRT will be applied only on Prostate: 2 times 10 Gy delivered to the prostate with a gap of one week between each SBRT fraction. |
| ADT (Standard of Care) | DRUG | Androgen Deprivation Therapy (ADT) The ADT treatment will be chosen at the investigator's discretion, and will be administered according to local standard procedures for up to 2 years. Patients who may have received ADT prior joining the study should have started the ADT treatment within a maximum of 6 weeks before randomization. Otherwise ADT will be started on Day 1 (or 14 days at the latest after the randomization). |
| radiotherapy | RADIATION | Following randomization, patients will receive dose escalated intensity modulated radiotherapy (IMRT) using normo-fractionation or moderate hypo-fractionation including whole pelvic nodal radiotherapy (WPRT). Arm A and Arm B: If Normo-fractionated radiotherapy: Pelvic nodes 46 Gy, seminal vesicles 46-54 Gy and prostate 78 Gy (39 fractions over 8 weeks). If Hypo-fractionated radiotherapy: Pelvic nodes and seminal vesicles 44 Gy in 20 fractions; prostate 60 Gy delivered concomitantly in 20 fractions over 4 weeks. Arm C and Arm D: If Normo-fractionated radiotherapy: Pelvic nodes 46 Gy, seminal vesicles 46 Gy in 23 fractions over 4.5 weeks. If Hypo-fractionated radiotherapy: Pelvic nodes and seminal vesicles 44 Gy in 20 fractions over 4 weeks. |
| Darolutamide (BAY1841788, Nubeqa) | DRUG | Coated tablet, 300 mg / tablet, oral. |
| Placebo matching darolutamide | OTHER | Coated tablet, oral |
| ADT | OTHER | Luteinizing hormone-releasing hormone \[LHRH\] agonist/antagonists |
| Darolutamide 300 mg | DRUG | Darolutamide regimen will be of 2 tablets of 300 mg orally twice daily for 24 months. |
| Placebo of Darolutamide | DRUG | Placebo of Darolutamide regimen will be of 2 tablets of 300 mg orally twice daily for 24 months. |
| Darolutamide (Nubeqa, BAY1841788) | DRUG | Coated tablet, oral administration |
| Placebo | DRUG | Coated tablet matching Darolutamide in appearance, oral administration |
| Androgen deprivation therapy (ADT) | OTHER | Luteinizing hormone-releasing hormone (LHRH) agonist/antagonists or orchiectomy |
| Placebo oral tablet | DRUG | 2 oral tablets twice daily for 96 weeks |
| Luteinizing Hormone-Releasing Hormone Analog | DRUG | All participants are to receive standard background therapy with an LHRHA, as per standard of care. The choice of LHRHA is at the discretion of the treating clinician. |
| External Beam Radiotherapy | RADIATION | All participants are to receive standard background therapy with curative-intent RT to the prostate or prostate bed as well as the pelvic lymph nodes using EBRT. |
| docetaxel | DRUG | Docetaxel: intravenous injection, 75 mg/m², once every 3 weeks, for a total of 4 doses/cycles. (Oral prednisone acetate should be started 14 days before docetaxel chemotherapy at 5 mg twice daily and discontinued 3 weeks after the last chemotherapy cycle.) |
| Degarelix | DRUG | Degarelix is administered by subcutaneous injection. The first dose of degarelix is 240 mg followed by monthly doses of 80 mg for a total treatment duration of 6 months. |
| Radiation Therapy | RADIATION | The total radiotherapy dose for all subjects will be: 36.25 Gy in 5Fx. The study will not include elective nodal irradiation. Every fraction will have 3D image guidance (i.e. cone-beam CT). |
| Darolutamide(BAY1841788, Nubeqa) | DRUG | tablet, oral |
| Enzalutamide | DRUG | tablet, oral |
| Goserelin | DRUG | Goserelin at a dose of 3.6 mg will be administered subcutaneously every 4 weeks. |
| Darolutamide (BAY1841788) | DRUG | 300 mg tablet darolutamide, once orally |
Inclusion Criteria: 1. Signed a written informed consent form prior to any trial specific procedures Note: In case of physical incapacitation, a trusted representative of their choice, which is not the investigator or sponsor, can sign on the behalf of the patients 2. Men, 18 years ≤ Age ≤ 80 y...
Darolutamide is an investigational small molecule being studied for the treatment of prostate cancer, including high-risk non-metastatic castration-resistant prostate cancer, metastatic hormone-sensitive prostate cancer, and high-risk localized prostate cancer. It is also being evaluated in salivary gland cancer and cerebrovascular circulation conditions. The drug is currently in Phase 3 clinical development.
Darolutamide is an androgen receptor inhibitor. It works by blocking the effects of androgens, such as testosterone, on the androgen receptor, which can slow the growth of prostate cancer cells. This mechanism is being studied across multiple prostate cancer indications.
Darolutamide is being developed by Bayer AG, a German pharmaceutical company. Bayer's stock is traded over-the-counter under the ticker symbol BAYRY. The company is conducting multiple clinical trials to evaluate the drug's efficacy and safety in various prostate cancer settings.
Darolutamide is in Phase 3 clinical development. It is an investigational drug and has not been approved by regulatory authorities. The drug is being studied in several Phase 3 trials for prostate cancer, including non-metastatic castration-resistant prostate cancer and metastatic hormone-sensitive prostate cancer.
Darolutamide is being evaluated in four clinical trials. NCT02200614 is a completed Phase 3 study in high-risk non-metastatic castration-resistant prostate cancer with 1,509 participants. NCT04464226 is an active Phase 3 extension study with 402 participants. NCT04736199 is a completed Phase 3 trial in metastatic hormone-sensitive prostate cancer with 669 participants. NCT07450599 is a recruiting Phase 2 study in high-risk localized prostate cancer with 250 participants.
Yes, Darolutamide is also known as Nubeqa and BAY1841788. These names refer to the same drug substance. The drug is being developed by Bayer AG under these various names, and it is also referred to as standard Darolutamide or Darolutamide oral tablet in clinical contexts.