Prostate Androgen Response Investigation Using a Stratification BIOmarker; Predicting Prostate Cancer Downstaging by Neoadjuvant Darolutamide With PCAI ImmunoScore (PARIS-BIO)

PARIS-BIO - Prostate Androgen Response Investigation Using a Stratification BIOmarker; Predicting Prostate Cancer Downstaging by Neoadjuvant Darolutamide With PCAI ImmunoScore in a Non-randomised Open Label Prospective Trial

The PARIS-BIO study evaluates whether a novel genomic biomarker, the PCAI ImmunoScore, can predict the response to neoadjuvant treatment with Darolutamide in patients with high-risk localized or locally advanced prostate cancer. Patients will receive Darolutamide monotherapy for 90-120 days prior to radical prostatectomy. The study aims to validate if the biomarker can identify patients who achieve Minimal Residual Disease (MRD) at the time of surgery.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer (Adenocarcinoma)
• Intervention / Treatment: Drug: Darolutamide; Procedure: Radical prostatectomy

Detailed Description

High-risk prostate cancer patients are at risk for recurrence after local therapy. The presence of micro-metastatic disease, undetectable by conventional imaging, likely contributes to the poor prognosis. Neoadjuvant hormonal therapy, particularly with the advent of ARPIs like Darolutamide, has shown promise, but patient selection remains crucial for optimizing outcomes. This Phase II, single-arm, open-label trial investigates the predictive value of the PCAI ImmunoScore, a gene expression signature derived from diagnostic biopsies.

100 participants with high-risk prostate cancer scheduled for radical prostatectomy will be enrolled. They will receive Darolutamide (600 mg twice daily) for a period of 90 to 120 days. MRI imaging will be performed between day 90 and 120 prior to surgery. Radical prostatectomy is performed within the same window.

The primary analysis compares the pre-treatment biomarker score with the pathological response (Minimal Residual Disease) observed in the surgical specimen. Secondary analyses include MRI response, PSA kinetics, and patient-reported functional outcomes.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Per H Vincent, MScEng, PhD; Phone Number: +46(0)708239320; Email: per.vincent@regionstockholm.se
• Study Contact Backup: Name: Sara Göransson, PhD; Phone Number: +46(0)812377000; Email: sara.goransson@regionstockholm.se

Study Locations

• Sweden
  • Gothenburg, Sweden
    • Recruiting
    • Sahlgrenska University Hospital
    • Contact: Johan Stranne, MD, Professor; Phone Number: +46(0)709558865; Email: johan.stranne@vgregion.se
    • Principal Investigator: Johan Stranne, MD, Professor
  • Stockholm, Sweden, SE-17176
    • Recruiting
    • Karolinska University Hospital
    • Contact: Johan Björklund, MD, PhD; Phone Number: +46(0)709583113; Email: johan.bjorklund@regionstockholm.se
    • Contact: Axel Möller, MD, PhD; Phone Number: +46(0)706271734; Email: axel.moller@regionstockholm.se
    • Principal Investigator: Johan Björklund, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Biopsy-confirmed high-risk prostate cancer defined as: Global ISUP score > 3 with any MRI PI-RADS score OR Global ISUP score = 3 with MRI PI-RADS score = 5
• Candidate for radical prostatectomy
• Clinical prostate MRI not older than 3 months at screening
• ECOG performance status score of 0 or 1
• Able to receive Darolutamide for 90-120 days
• Signed informed consent form
• Willingness to use contraception if sexually active

Exclusion Criteria:

• Metastatic (M1) or node-positive (N2) disease
• Prior treatment with androgen receptor antagonists
• Prior treatment with gonadotropin-releasing hormone (GnRH)
• History of prior systemic or local therapy for prostate cancer (including radiation and focal therapy)
• Major surgery <4 weeks prior to inclusion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Neoadjuvant Darolutamide; All participants receive Darolutamide 600 mg orally twice daily for 90-120 days prior to radical prostatectomy

Drug: Darolutamide; Neoadjuvant Darolutamide alone (without ADT) 2x300 mg orally twice daily is given to all study subjects for 90-120 days prior to prostatectomy.; Other Names: Nubeqa; Neoadjuvant ARPI; Procedure: Radical prostatectomy; Robot-assisted radical prostatectomy, with or without extirpation of pelvic lymph nodes according to clinician's choice in concordance with local guidelines; Other Names: RALP; RARP; Robot-assisted prostatectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The association between the pre-treatment probability of treatment response given by PCAI ImmunoScore and the occurrence of minimal residual disease (MRD)	The primary outcome is the association between the pre-treatment PCAI ImmunoScore and the occurrence of minimal residual disease (MRD) after 90-120 days of neoadjuvant Darolutamide treatment. MRD is defined as < 0.05 cm3 residual tumour on final pathology after prostatectomy. The study endpoint MRD will be dichotomized into responder (if MRD is met) or non-responder (if MRD is not met) as input for the statistical data analysis. This classification (ground truth) will be tested in AUROC analysis against the calculated PCAI ImmunoScore-based probability p (0<p<1) of Darolutamide response. PCAI ImmunScore is calculated from RNA sequencing of tumor material from diagnostic (pre-treatment) biopsies. The collection of RNA and calculation of PCAI ImmunoScore will take place after the recruitment period. Sequencing will be performed in bulk once all samples have been collected. The objective is to assess the predictive value of the pre-treatment genomic biomarker for pathological response.	MRD is ascertained shortly after radical prostatectomy (day 90-120). PCAI ImmunoScore will be ascertained after bulk sequencing of all samples, tentatively 1 year after surgery of the 100th study subject. The association will be calculated thereafter.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The association between PCAI ImmunoScore and pathologic complete response (pCR)	The study endpoint pCR is defined as no residual tumour visible at final pathology and will be dichotomized into responder (if pCR is met) or non-responder (if pCR is not met) as input for the statistical data analysis. This classification (ground truth) will be tested in AUROC analysis against the calculated PCAI ImmunoScore-based probability p (0<p<1) (baseline model) of Darolutamide response. The extended model including the additional covariates will be tested equivalent to the baseline model.	pCR is ascertained shortly after radical prostatectomy (day 90-120). PCAI ImmunoScore will be ascertained after bulk sequencing of all samples, tentatively 1 year after surgery of the 100th study subject. The association will be calculated thereafter.
Pathological T-stage (pT-stage)	Staging of the tumor at final pathology	Pathological T-stage will be ascertained shortly after radical prostatectomy (day 90-120)
Residual tumor size	Measurement of the largest cross-sectional dimensions (mm) of residual tumor	At the time of radical prostatectomy (day 90-120)
PSA Kinetics	Change in blood PSA concentration (ng/ml) during treatment	Baseline, Day 30, Day 60, Day 90, and within 4 weeks after surgery
Hormonal side effects	Incidence and severity of adverse events assessed by CTCAE v5.0 and patient-reported quality-of-life using the 26-question questionnaire Expanded Prostate cancer Index Composite (EPIC-26), where lower scores indicate worse outcome	From baseline up to 12 months post-surgery
Patient-reported urinary continence	Assessment of pre-and post-treatment urinary function using the Swedish national questionnaires (electronic patient-reported outcome measurements -ePROM "Symtom- och biverkningsenkät" that all patients undergoing prostate cancer treatment in Sweden routinely are invited to answer), where urinary continence is assessed using the question "How many protective pads do you use daily due to urine leakage?" The reply alternatives are: None Fewer than 1 per day About 1 per day About 2 per day About 3-4 per day About 5 or more per day	Pre-surgery (day 80-119), 3 months post-surgery, 12 months post-surgery
Patient-reported erectile function	Assessment of pre-and post-treatment erectile function using the Swedish national questionnaires (electronic patient-reported outcome measurements -ePROM "Symtom- och biverkningsenkät" that all patients undergoing prostate cancer treatment in Sweden routinely are invited to answer), where erectile function is assessed using the question "How would you describe your erection?" The reply alternatives are: No noticeable filling or firmness Some filling, but not sufficient for full function Moderate firmness Full firmness	Pre-surgery (day 80-119), 3 months post-surgery, 12 months post-surgery
MRI tumor response	Change in tumor size and Extraprostatic Extension (EPE) score (Likert scale 1-5) on MRI compared to baseline MRI	Pre-surgery (day 90-120)

Collaborators and Investigators

• Sponsor: Region Stockholm
• Collaborators: Bayer; Sahlgrenska University Hospital; Philips Intellectual Property & Standards; OHMX.bio; Innovative Health Initiative - European Union
• Investigators: Principal Investigator: Peter N Wiklund, MD, Professor, Region Stockholm represented by Karolinska University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: December 12, 2025
• First Submitted That Met QC Criteria: May 24, 2026
• First Posted (Actual): June 1, 2026

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 24, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Prostate cancer; Neoadjuvant; Darolutamide; Prediction of treatment response; ARPI
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Prostatic Neoplasms; Adenocarcinoma; darolutamide
• Other Study ID Numbers: 5.1.1-2025-027483; 2025-520639-17-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No