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
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.
Subjects with metastatic disease
Subjects with Gleason score ≤7 (3+4)
Subjects with Biopsy Decipher score ≤0.45.
Subjects have had prior hormonal therapy (please see inclusion criteria for exceptions).
Icahn School of Medicine at Mount Sinai
Lead sponsor
Merck Sharp & Dohme LLC
Collaborator
Bayer
Collaborator