Actively Recruiting
Neoadjuvant ADT + Darolutamide With Pembrolizumab, Followed by Adjuvant Pembrolizumab in Molecularly Stratified High-Risk Prostate Cancer
Led by Icahn School of Medicine at Mount Sinai · Updated on 2026-03-19
40
Participants Needed
1
Research Sites
267 weeks
Total Duration
On this page
Sponsors
I
Icahn School of Medicine at Mount Sinai
Lead Sponsor
M
Merck Sharp & Dohme LLC
Collaborating Sponsor
AI-Summary
What this Trial Is About
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
CONDITIONS
Official Title
Neoadjuvant ADT + Darolutamide With Pembrolizumab, Followed by Adjuvant Pembrolizumab in Molecularly Stratified High-Risk Prostate Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Male age 18 years or older at the time of consent
- Histologically confirmed adenocarcinoma of the prostate
- NCCN high-risk localized or locally advanced prostate cancer without distant metastasis or nodal involvement
- Gleason score 8 or higher, or PSA above 20 ng/ml, or clinical stage cT3a or higher
- Cancer must have all three molecular features: Decipher Genomic Classifier above 0.6, AR activity score above 11, and Luminal B subtype
- Performance status of 0-1 by Eastern Cooperative Oncology Group criteria
- Prior neoadjuvant hormonal therapy allowed if completed at least 12 months ago and recovered from adverse events
- Recovery from any prior major surgery complications before enrollment
- Adequate organ and marrow function as specified (e.g., ANC ≥ 1,500/mcL, platelets ≥ 100,000/mcL, hemoglobin ≥ 9 g/dL)
- Men must agree to use condoms and not father a child or donate sperm during the study and for 90 days after
- Willingness and ability to provide informed consent
- Hepatitis B positive participants must be on antiviral therapy with undetectable viral load
- Hepatitis C participants eligible if viral load undetectable and completed therapy at least 4 weeks before
- HIV positive participants eligible if stable on ART for at least 12 weeks with undetectable viral load
You will not qualify if you...
- Presence of metastatic disease
- Gleason score below 8
- Biopsy Decipher score 0.6 or lower
- Prior hormonal therapy not meeting inclusion exceptions
- Prior radiation therapy or chemotherapy for prostate cancer
- Active cardiac disease or cardiac events within 6 months before treatment
- Active gastrointestinal disorders affecting drug absorption
- Prior treatment with androgen receptor inhibitors or investigational CYP17 inhibitors
- Inability to swallow oral medications
- Active infections requiring systemic therapy within 7 days before treatment
- Previous therapy with checkpoint inhibitors or T-cell costimulatory/inhibitory agents
- Active viral Hepatitis B or C infection, or untreated chronic liver disease
- Active or history of tuberculosis or non-infectious pneumonitis
- Immunodeficiency or recent systemic steroid or immunosuppressive therapy
- Active autoimmune disease requiring systemic therapy within past 2 years
- Conditions or treatments that could confound study results
- Psychiatric, epileptic, or substance abuse disorders interfering with study compliance
- Known brain metastases
- Allergy to study agents or similar compounds
AI-Screening
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Trial Site Locations
Total: 1 location
1
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10028
Actively Recruiting
Research Team
D
Daniela Delbeau- Zagelbaum, RN, NP
CONTACT
M
Monali Fatterpekar, PhD
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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