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

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

Inclusion Criteria: * 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. 1. Decipher Genomic Classifier \>0.45 (interpreted from decipher report) and/ or 2. Luminal B subtype (interpreted from decipher report). * 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 \