NCT07027124

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

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Icahn School of Medicine at Mount Sinai · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

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 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

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.

Conditions

• Prostate Cancer
• High-risk Prostate Cancer

Interventions

Type	Name	Description
DRUG	Darolutamide	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.
DRUG	Pembrolizumab	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
DRUG	Lupron	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).

Timeline

• Start date: 2026-03-19
• Primary completion: 2026-12-01
• Completion: 2031-05-02
• First posted: 2025-06-18
• Last updated: 2026-03-19

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study