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

What Was Tested

In this phase 2 trial, researchers set out to test Leuprolide.

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.

It had 1 arm (groups): Participants with Prostate Cancer (experimental).

Neoadjuvant 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.

The registry classes the interventions as drug.

More on the Plan

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.

Who Took Part

The registry lists 40 planned participants were the target.

It was open to men only aged from 18 years with no upper age limit.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could 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.

The full record lists 32 inclusion and 21 exclusion criteria; among the exclusions: subjects with metastatic disease; subjects with gleason score ≤7 (3+4); subjects with biopsy decipher score ≤0.45.

How the Study Was Run

It was run as a single-group and open-label study.

Everyone knew when Leuprolide was being given (open label), which is simpler to run but leaves more room for expectations to affect what is reported.

Everyone received the same intervention, so there was no separate comparison group inside the trial.

It started in 2026-05-21 with completion listed for 2027-12-01.

It ran at 1 site in United States.

Its stated primary purpose is treatment.

What Was Measured

The main thing measured (primary outcome): Proportion of patients who achieve Minimal residual disease (MRD) (time frame: at time of surgery (At Week 17)).

It also tracked 9 secondary outcomes, for example Complete pathological response (pCR), Proportion of patients who had had their tumor downstaged, Adverse events assessed by NCI CTCAE (v.5.0), Biochemical progression free survival bPES, Metastasis free survival (MFS) and Tumor Volumes.

What This Means in Plain Language

Put simply, this is a phase 2 trial of Leuprolide in 40 people.

It is still recruiting; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the Leuprolide compound page, all human trials.