Study of Darolutamide and Pembrolizumab for High-Risk Prostate Cancer
This study is for men with high-risk prostate cancer that has not spread. It is testing a combination of treatments given before surgery, followed by more treatment after surgery. Before surgery, you would receive Darolutamide (an androgen receptor blocker), Lupron (a hormone therapy), and Pembrolizumab (an immunotherapy). After surgery, you would continue with Pembrolizumab. Researchers want to see if this treatment combination leads to very little cancer remaining at the time of surgery (minimal residual disease). The study plans to enroll 40 men aged 18 or older who have been diagnosed with high-risk prostate cancer based on specific criteria like Gleason score and PSA levels.
- Study design
- This is a single-arm study, meaning all participants receive the same treatment. It aims to enroll 40 men.
- What's involved
- You would receive Darolutamide and Lupron for 16 weeks before surgery, and Pembrolizumab for 5 cycles before surgery and 12 cycles after surgery. The primary endpoint is measured at the time of surgery (Week 17).
- Compensation
- Not stated in the trial record.
- Follow-up
- The primary endpoint is measured at the time of surgery (Week 17). Pembrolizumab treatment continues for 12 cycles post-surgery, with the last cycle at Week 52.
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NCT07027124
Neoadjuvant ADT + Darolutamide With Pembrolizumab, Followed by Adjuvant Pembrolizumab in Molecularly Stratified High-Risk Prostate Cancer
Recruiting
PHASE2Ages 18+InterventionalTreatmentIcahn School of Medicine at Mount SinaiInvestigator-initiated
~40 participants
Updated 2026-06-16 on ClinicalTrials.gov
What's tested:DarolutamidePembrolizumabLupron
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Proportion of patients who achieve Minimal residual disease (MRD)
Measured over at time of surgery (At Week 17)
Conditions
Where it's being run
1 sites across 1 statesNew York1
Study leadership
- Ashutosh K Tewari, MD · PRINCIPAL_INVESTIGATOR · Icahn School of Medicine at Mount Sinai
- Dimple Chakravarty, PhD · PRINCIPAL_INVESTIGATOR · Icahn School of Medicine at Mount Sinai
Who to contact
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Do you actually qualify for this trial?
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Eligibility criteria
Inclusion
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.
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.
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.
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.
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:
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.
Exclusion
Subjects with metastatic disease
Subjects with Gleason score ≤7 (3+4)
Subjects with Biopsy Decipher score ≤0.45.
What this trial measures
- Proportion of patients who achieve Minimal residual disease (MRD)at time of surgery (At Week 17)
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.