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Prostate CancerPhase 2NCT07027124

Neoadjuvant ADT + Darolutamide With Pembrolizumab, Followed by Adjuvant Pembrolizumab in Molecularly Stratified High-Risk Prostate Cancer

A Phase 2 study testing Darolutamide, Pembrolizumab and Lupron in people with Prostate Cancer and High-risk Prostate Cancer, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This is a single-arm, phase II study of neoadjuvant combination therapy of Androgen Deprivation Therapy (ADT), [Gonadotropin-Releasing Hormone (GnRH) agonist Leuprolide], androgen receptor (AR)-antagonist Darolutamide and Pembrolizumab in a stratified high-risk localized prostate cancer cohort, followed by adjuvant… Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Cancer, High-risk Prostate Cancer
What is being tested?
Darolutamide, Pembrolizumab and Lupron
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteUnited States
Study dates
21 May 2026to 2 May 2031
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male Age ≥ 18 years at the time of consent
  • Subjects must have histopathologically confirmed adenocarcinoma of the prostate
  • Subjects must have unfavorable intermediate and high-risk localized or locally advanced prostate cancer (Gleason score ≥7 (4+3) and absence of distant metastasis or non-regional nodal involvement.
  • Subjects must be risk-stratified at biopsy and their cancer should have all the molecular features given below at baseline.
  • Decipher Genomic Classifier >0.45 (interpreted from decipher report) and/ or
  • Luminal B subtype (interpreted from decipher report).
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  • The patient must have a performance status of 0-1 as determined by criteria set forward by the eastern cooperative oncology group.
  • Subjects with prior neoadjuvant hormonal therapy are allowed if they meet the following criteria.
  • have completed all treatments ≥ 12, months ago.
  • Recovered from all AEs due to previous therapies.
  • If subject has had a major surgery, he should have recovered from all complications and toxicities prior to enrolling in the study.
  • Adequate organ and marrow function as defined below:
  • Hematological
  • Absolute neutrophil count (ANC) ≥ 1,500/mcL
  • Platelets ≥ 100,000/mcl
  • Hemoglobin (Hb) ≥ 9 g/dL Hepatic
  • total bilirubin ≤ 1.5 mg/dl (except in patients with gilbert syndrome who can have total bilirubin <3.0 mg/dl)
  • Aspartate aminotransferase (AST) ≤ 2.5 x ULN
  • Alanine aminotransferase (ALT) ≤ 2.5 x ULN Renal
  • Creatinine OR Creatinine ≤ 1.5 ULN OR
  • Calculated creatinine clearance Creatinine clearance ≥ 30 ml/min
  • Men must agree to use a condom and not father a child or donate sperm for the duration of the study and for 90 days after completion of therapy. Subject must agree to partner use of an additional contraceptive method when having intercourse with women of childbearing potential (WOCBP).
  • Ability to understand and the willingness to sign a written informed consent.
  • Subjects who are HBs Ag positive are eligible if they have received HBV anti-viral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization.
  • Note: Subjects should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention.
  • Hepatitis B screening tests are not required unless:
  • Known history of HBV infection
  • As mandated by local health authority
  • Subjects with a history of HCV infection are eligible if HCV viral load is undetectable at screening.
  • Note: Subjects must have completed curative anti-viral therapy at least 4 weeks prior to randomization.
  • Hepatitis C screening tests are not required unless:
  • Known history of HCV infection
  • As mandated by local health authority
  • Subjects with a known history of Human immunodeficiency virus (HIV) infection are eligible as long as they have an undetectable viral. HIV positive participants must be taking stable ART for ≥ 12 weeks and have an undetectable HIV viral load within 28 days before enrollment. Minor fluctuations up to 200 copies/mL are acceptable.

Who cannot join

  • Subjects with metastatic disease
  • Subjects with Gleason score ≤7 (3+4)
  • Subjects with Biopsy Decipher score ≤0.45.
  • Subjects have had prior hormonal therapy (please see inclusion criteria for exceptions).
  • Subjects have had prior radiation therapy or chemotherapy for prostate cancer.
  • Subjects with active cardiac disease defined as having any of the following within 6 months prior to the start of treatment:
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  • myocardial infarction,
  • severe/unstable angina pectoris,
  • congestive heart failure,
  • hospitalization for any cardiac event
  • Subject has active GI disorder that will interfere with absorption of study drug Darolutamide Subject has prior treatment with androgen receptor inhibitors, such as apalutamide, Darolutamide, enzalutamide, abiraterone acetate or other investigational CYP17 inhibitor.
  • Inability to swallow oral medications.
  • Subject has active infection requiring systemic therapy within 7 days of Week 1.
  • Subject has received prior therapy with anti-PD1, anti-PDL1, anti-PDL2 or with other checkpoint inhibitors or T-cell costimulatory/inhibitory agents (e.g., CD137, OX-40, CTLA4).
  • Subject with an active viral Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive or detectable [qualitative] Hepatitis b virus [HBV] DNA or defined as Hepatitis V virus [HCV] ribonucleic acid [RNA] [qualitative] is detected), known Human Immunodeficiency virus (HIV) infection with detectable viral load, or chronic liver disease with a need of treatment.
  • Subject has a known active or known history of TB (Bacillus tuberculosis) or active history of non-infectious pneumonitis.
  • Subject who are immunodeficient or are receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days of study intervention. Topical or inhaled steroids are permitted in absence of immunodeficiency or autoimmune disease.
  • Subject have active auto-immune disease that has required systemic therapy (use of disease modifying agents, corticosteroids, or immunosuppressive drugs) in the past 2 years. However, subjects receiving replacement therapy (e.g., insulin, thyroxine, or physiological corticosteroid replacement therapy for adrenal and pituitary insufficiency) are eligible.
  • Has history or current evidence of any condition, therapy that might confound results of the study. - Has known psychiatric, epileptic or substance abuse history or disorder that would interfere with participant's ability to cooperate with the requirements of the study.
  • Subjects with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • Known history of allergic reactions attributed to compounds of similar chemical or biologic composition to Agent(s) or other agents used in study.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Daniela Delbeau- Zagelbaum, RN, NP contact

212 241 2066

daniela.delbeau-zagelbaum@mssm.edu

Monali Fatterpekar, PhD contact

212 241 0751

monali.fatterpekar@mountsinai.org

United States1 site, 1 recruiting

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10028

    Darren Deoraj, MHA, darren.deoraj@mountsinai.org

    Ashutosh Tewari, MD

    Recruiting

Other trials in United States

About this study

Official title: Neoadjuvant ADT and Darolutamide With Pembrolizumab, Followed by Adjuvant Pembrolizumab in NCCN High-risk and Molecularly Stratified Prostate Cancer Patients

This is a single-arm, phase II study of neoadjuvant combination therapy of Androgen Deprivation Therapy (ADT), [Gonadotropin-Releasing Hormone (GnRH) agonist Leuprolide], androgen receptor (AR)-antagonist Darolutamide and Pembrolizumab in a stratified high-risk localized prostate cancer cohort, followed by adjuvant treatment with Pembrolizumab (12 cycles) post-radical prostatectomy (RP).

Patients with National Comprehensive Cancer Network (NCCN) high-risk non-metastatic prostate cancer (localized or locally advanced) (defined as Gleason ≥8, disease stage >=cT3a, or PSA l >20 ng/mL) will be risk-stratified at a biopsy using Decipher, a commercial standard-of-care diagnostic assay. Patients satisfying all three criteria of high-risk genomic characteristics listed below as per the Decipher grid results will be enrolled in the study:

  1. Decipher Genomic classifier, GC>0.6
  2. AR activity score/AR-output gene signature (ARoS)>11.0
  3. High Luminal B score/ PAM50 subtype signature
Read the detailed description

The objectives of this study are to evaluate if the neoadjuvant ADT, Darolutamide and Pembrolizumab treatment in high-risk prostate cancer patients stratified based on their genomic characteristics will lead to minimum residual disease (MRD).

A total of 40 men ≥ 18 years of age with non-metastatic adenocarcinoma of the prostate, having NCCN high risk localized disease, risk stratified at biopsy based on Decipher score, AR activity score and Luminal B score will be enrolled.

Being tested
Darolutamide, Pembrolizumab, Lupron
Keywords
Prostate Cancer, Immunotherapy, Pembrolizumab, Darolutamide, ADT
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DarolutamideDrug

    Also called Nubeqa

    Darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equivalent to a total daily dose of 1200 mg for 16 weeks prior to RP.

  • PembrolizumabDrug

    Also called Keytruda

    Administered at the dose of 200 mg intravenously, every 3 weeks, for a total of 5 cycles prior to RP (Neoadjuvant phase, study weeks 1, 4, 7, 10, 13 \& 16), and every 3 weeks, for a total of 12 cycles post-RP (Adjuvant phase, study weeks, 19, 22, 25, 28, 31, 34, 37, 40 43, 46, 49, \& 52). Total Pembrolizumab cycles=17

  • LupronDrug

    Also called Leuprolide

    Androgen deprivation, GnRH agonist Leuprolide will be administered at a dose of 22.5 mg SQ (Eligard)/IM Lupron every 12 weeks prior to RP (Study weeks, 1 and 13).

Study groups in NCT07027124
Study groupRoleWhat they receive
Participants with Prostate CancerExperimentalNeoadjuvant ADT plus AR- antagonist, Darolutamide plus Pembrolizumab (5 cycles) prior to radical prostatectomy (RP) in a stratified high-risk localized prostate cancer cohort, followed by adjuvant treatment with Pembrolizumab (12 cycles) post-RP.
Receives: Drug: Darolutamide; Drug: Pembrolizumab; Drug: Lupron

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of patients who achieve Minimal residual disease (MRD)

    MRD is defined as residual cancer burden (RCB) ≤0.25cm³ at final pathology, where RCB is calculated by multiplying the residual tumor volume with the tumor cellularity. The proportion of patients who achieve MRD will be collected at the time of surgery.

    Measured: at time of surgery (At Week 17)

Secondary outcomes (9)

  1. Complete pathological response (pCR)

    Complete pathological response (pCR) is defined as the absence of viable tumor in post treatment prostatectomy specimens). pCR is typically determined by examining the radical prostatectomy specimen after surgery.

    Measured: After Week 17

  2. Proportion of patients who had had their tumor downstaged

    Proportion of patients who had had their tumor downstaged due to neoadjuvant Pembrolizumab, Darolutamide and ADT at the time of surgery. Downstaging will be determined using MRI and pathology separately.

    Measured: at time of surgery (At Week 17)

  3. Adverse events assessed by NCI CTCAE (v.5.0).

    Adverse events assessed by NCI CTCAE (v.5.0). Incidence of AEs will be reported for the first cycle of neoadjuvant therapy, for the entire neoadjuvant treatment phase, and for the adjuvant treatment phase.

    Measured: Week 1 to Week 16, Week 19 to Week 52

  4. Biochemical progression free survival bPES

    bPFS is defined as the time from baseline to first evidence of biochemical progression based on PSA level or death, whichever occurs first.

    Measured: Week 22 and until 5 years after Week 17

  5. Metastasis free survival (MFS)

    Metastasis free survival (MFS) defined as time from enrollment to detection of metastasis or death, whichever occurs first.

    Measured: Week 17 and until 5 years after Week 17

  6. Tumor Volumes

    Median tumor volumes assessed by MRI at baseline and before surgery (and the corresponding change in median tumor volume from baseline to before surgery).

    Measured: Week 0 to Week 17

  7. Immunological responses in blood

    A broad immunophenotyping panel will be used to define various immune subsets and their functional states, in pre-treatment and longitudinally collected whole blood samples. Longitudinally collected serum/plasma samples will be analyzed using Olink multiplex assay platform.

    Measured: Week 0 to Week 52

  8. Whole exome-sequencing (WES)

    Transcriptomic and genomic changes in tissues - Whole exome-sequencing (WES) will be performed for characterization of the mutational landscape including neoantigens and differentially expressed genes and gene signatures.

    Measured: Week 0 to Week 17

  9. RNA sequencing (RNA-seq)

    Transcriptomic and genomic changes in tissues - RNA sequencing (RNA-seq) will be performed for characterization of the mutational landscape including neoantigens and differentially expressed genes and gene signatures.

    Measured: Week 0 to Week 17

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jun 2025
  2. Study start21 May 2026
  3. Primary completion1 Dec 2027 (estimated)
  4. Study completion2 May 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07027124
Sponsor's protocol ID
STUDY-23-01400
Status last verified
Sep 2026
First submitted
10 Jun 2025
Last updated
7 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Darolutamide, Pembrolizumab and Lupron in people with Prostate Cancer and High-risk Prostate Cancer, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 34 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 7 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Daniela Delbeau- Zagelbaum, RN, NP (212 241 2066, daniela.delbeau-zagelbaum@mssm.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of patients who achieve Minimal residual disease (MRD) (time frame: at time of surgery (At Week 17)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07027124.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2026.

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