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OncoMatch/Clinical Trials/NCT07027124

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

Is NCT07027124 recruiting? Yes, currently enrolling (May 2026). This Phase 2 trial studies multiple treatments including Darolutamide and Pembrolizumab for prostate cancer.

Phase 2RecruitingIcahn School of Medicine at Mount SinaiNCT07027124Data as of May 2026

Treatment: Darolutamide · Pembrolizumab · LupronThis 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

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Extracted eligibility criteria

Cancer type

Prostate Cancer

Biomarker criteria

Required: AR high ar activity/ar activity score >11 (>11)

Disease stage

Required: Stage NCCN HIGH-RISK LOCALIZED, III (NCCN)

Excluded: Stage IV

NCCN high-risk localized or locally advanced prostate cancer and absence of distant metastasis or nodal involvement

Performance status

ECOG 0–1(Restricted strenuous activity)

Prior therapy

Cannot have received: hormonal therapy

Exception: prior neoadjuvant hormonal therapy allowed if completed ≥ 12 months ago and recovered from all AEs

Patients have had prior hormonal therapy (please see inclusion criteria for exceptions)

Cannot have received: radiation therapy

Patients have had prior radiation therapy or chemotherapy for prostate cancer

Cannot have received: cytotoxic chemotherapy

Patients have had prior radiation therapy or chemotherapy for prostate cancer

Cannot have received: androgen receptor inhibitor (apalutamide, darolutamide, enzalutamide, abiraterone acetate)

Subject has prior treatment with androgen receptor inhibitors, such as apalutamide, Darolutamide, enzalutamide, abiraterone acetate or other investigational CYP17 inhibitor

Cannot have received: anti-PD-1 therapy

Patients has received prior therapy with anti-PD1, anti-PDL1, anti-PDL2 or with other checkpoint inhibitors or T-cell costimulatory/inhibitory agents (e.g., CD137, OX-40, CTLA4)

Lab requirements

Blood counts

ANC ≥ 1,500/mcL; Platelets ≥ 100,000/mcl; Hemoglobin (Hb) ≥ 9 g/dL

Kidney function

Creatinine ≤ 1.5 ULN OR Creatinine clearance ≥ 30 ml/min

Liver function

total bilirubin ≤ 1.5 mg/dl (except in patients with Gilbert syndrome who can have total bilirubin <3.0 mg/dl); AST ≤ 2.5 x ULN; ALT ≤ 2.5 x ULN

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 <3.0 mg/dl) Aspartate aminotransferase (AST) ≤ 2.5 x ULN Alanine aminotransferase (ALT) ≤ 2.5 x ULN Renal Creatinine ≤ 1.5 ULN OR Calculated creatinine clearance ≥ 30 ml/min

Structured fields extracted by AI. May contain errors — verify against the official protocol.

US trial sites

  • Icahn School of Medicine at Mount Sinai · New York, New York

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