177Lu-PSMA-617 Combined With Darolutamide in Neoadjuvant Treatment of High-risk Localized Prostate Cancer: a Prospective, Single-arm, Multi-center Clinical Trial (IUNU-PC-123)

The goal of this clinical trial is to explore the efficacy and safety of darolutamide combined with 177Lu-PSMA-617 in treating high-risk localized prostate cancer patients who are scheduled to undergo radical prostatectomy. The main questions it aims to answer are:

Does this combination treatment improve the pathological complete response rate (pCR)? What is the minimal residual disease (MRD) rate in these patients? What are the safety profiles and any adverse effects associated with this treatment? Researchers will compare the combination of darolutamide and 177Lu-PSMA-617 to a placebo to see if the combination is effective in treating high-risk localized prostate cancer.

Participants will:

Receive either darolutamide combined with 177Lu-PSMA-617 or a placebo every day for 12 weeks.

Visit the clinic every 6 weeks for checkups and tests. Keep a diary of their symptoms and any side effects experienced during the treatment.

Undergo imaging tests, including prostate MRI and PSMA PET/CT, before surgery and during follow-up.

Study Overview

• Status: Not yet recruiting
• Conditions: Prostate Cancer; Prostate Cancer Patients
• Intervention / Treatment: Drug: Darolutamide combined with 177Lu-PSMA-617

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Hongqian Guo; Phone Number: +86 (025)-83106666; Email: dr.ghq@nju.edu.cn

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School
      • Contact: Hongqian Guo; Phone Number: +86 (025)-83106666; Email: dr.ghq@nju.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients must be ≥ 18 and ≤75 years of age
2. All patients must have a histologically or cytologically diagnosis of prostate cancer，without distant metastasis, and suitable for radical prostatectomy
3. All patients meet at least one of the following criteria： multi-parameter MRI or PSMA PET / CT shows clinical staging of primary tumor ≥ T2c； Gleason score of primary tumor ≥ 8； prostate specific antigen (PSA) ≥20 ng/ml； Radiographic assessment of regional lymph node metastases (N1)
4. Eastern Cooperative Oncology Group (ECOG) physical condition score 0- 1
5. Primary lesion SUVmax ≥ 20.0 as assessed by PSMA-PET examination.
6. Adequate organ function: Complete Blood Count: White blood cell count (WBC) ≥ 3.0 × 10^9/L, platelet count ≥ 100 × 10^9/L, hemoglobin ≥ 9 g/dL. Renal Function: Serum creatinine ≤ 2 × ULN. Liver Function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN, total bilirubin (TBIL) ≤ 1.5 × ULN. Coagulation Function: International normalized ratio (INR) < 1.5.
7. Voluntary Participation: Participants must voluntarily agree to participate and sign the informed consent form (ICF), indicating their understanding of the purpose of the study and the required procedures, as well as their willingness to participate in the research. Participants must be willing to comply with the prohibitions and restrictions outlined in the study protocol.
8. Patients of childbearing potential must be willing to take high-efficiency contraceptive measures during the study period and within 120 days after the last dose of treatment

Exclusion Criteria:

1. Patients with prostate having neuroendocrine, small cell, or sarcoma-like features are not eligible
2. Patients with low-risk and medium-risk, localized prostate cancer (the following conditions are met at the same time) are not eligible: prostate specific antigen (PSA) <20 ng/mL multiparameter MRI or PSMA PET / CT shows clinical staging of primary tumor < T3, Gleason score of primary tumor < 8
3. Patients with clinical or radiological evidence of regional or extra-regional lymph node metastases or bone metastases or visceral metastases (any M1）
4. Primary lesion SUVmax < 20.0 as assessed by PSMA-PET examination.
5. Patients who have previously received androgen deprivation therapy (medical or surgical) more than 3 months or focal treatment of prostate cancer or prostate cancer radiotherapy or prostate cancer chemotherapy
6. Patients with severe or uncontrolled concurrent infections
7. Patients must not have New York Heart Association Class III or IV congestive heart failure at the time of screening. Patients must not have any thromboembolic event, unstable angina pectoris, myocardial infarction within 6 months prior to registration
8. Uncontrolled severe hypertension, persistently uncontrolled diabetes, oxygen-dependent lung disease, chronic liver disease, or HIV infection
9. Patients with a history of other malignancies within the past 5 years, except for prostate cancer, are not eligible; however, cured basal cell carcinoma or squamous cell carcinoma of the skin may be eligible
10. Patients with mental illness, mental disability, or inability to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: Experimental Arm

Drug: Darolutamide combined with 177Lu-PSMA-617; 177Lu-PSMA-617: Eligible participants must start receiving 177Lu-PSMA-617 within 14 days. Participants will receive a dosage of 7.4 GBq (± 10%) of 177Lu-PSMA-617, administered once every 6 weeks (± 7 days), for a total of two doses. Darolutamide: Administered at a dosage of 1200 mg orally in two divided doses with meals, starting from the first injection of 177Lu-PSMA-617 and continuing until 6 weeks after the second injection, for a total duration of 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR + MRD	pCR + MRD (pCR: Pathological Complete Response; Minimal Residual Disease (MRD) rate: defined as the proportion of patients achieving MRD among all patients; MRD is defined as postoperative pathology indicating that the longest diameter of the tumor is ≤ 5 mm)	Screening, End of Neoadjuvant Treatment( 12 weeks after baseline)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Sexual Function	The International Index of Erectile Function (IIEF-5) will be used for assessment. This scale consists of five questions, with each question scored from 0 to 5, resulting in a total score range of 0 to 25. A total score greater than 21 indicates normal erectile function; a score of 12 to 21 indicates mild erectile dysfunction; a score of 8 to 11 indicates moderate erectile dysfunction; and a score of 1 to 7 indicates severe erectile dysfunction.	Day 1 of Cycle 1&2 ( each cycle is 6 weeks), 1 month after treatment, 3 and 6 months after treatment, 6 months until 2 years
PSA Response Rate (defined as a decrease in PSA of 50% or more)		Day 1 of Cycle 1&2 (each cycle is 6 weeks), End of Neoadjuvant Treatment (12 weeks after baseline). The last week of each month for the first 3 months after the periprocedural, thereafter the last week of every 3rd month for a total duration of 1 year
PSMA Response Rate	PSMA Response Rate: The assessment of PSMA response will be conducted using PSMA PET/CT at 6 weeks after treatment with 177Lu-PSMA-617. If all PSMA lesions have disappeared, it is classified as PSMA complete response. If the SUVmax (maximum standardized uptake value) decreases by more than 30%, it is classified as partial response. If the SUVmax increases by more than 30% or new PSMA-avid lesions appear, it is classified as disease progression. If the response does not meet the criteria for complete response, partial response, or disease progression, it is classified as stable disease.	Screening, End of Neoadjuvant Treatment (12 weeks after baseline)
1-year biochemical recurrence-free survival, bRFS	1-year Biochemical Recurrence-Free Survival (bRFS): Biochemical recurrence is defined as the occurrence of PSA levels exceeding 0.2 ng/ml in two consecutive tests after radical prostatectomy, with no evidence of recurrence or metastasis on imaging.	The last week of each month for the first 3 months after the periprocedural, thereafter the last week of every 3rd month for a total duration of 1 year
Perioperative Complications		Perioperative Period
Patient Quality of Life	The FACT-P scale (39 items) will be used for assessment. This scale includes a general functional status scale (composed of four subscales: physical, social and family, emotional, and functional) and a prostate cancer-specific subscale. The total score is calculated from the general functional and prostate cancer-specific scores, with a range from 0 to 156; a higher score indicates better functional status.	Day 1 of Cycle 1&2 ( each cycle is 6 weeks), 1 month after treatment, 3 and 6 months after treatmnet,6 months until 2 years
Tumor Radiation Absorbed Dose: The maximum absorbed dose of 177Lu-PSMA-617 treatment for the prostate (measured in Gray [Gy])		Screening, End of Neoadjuvant Treatment(12 weeks after baseline)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Event	All adverse events (AEs) will be assessed and graded according to NCI-CTCAE v5.0. Safety evaluations will be conducted and recorded after the initiation of the study drug, regardless of their relationship to the study drug, until 30 days after the last study treatment or the start of new anticancer therapy (whichever occurs first).	From Day 1 of cycle 1 to the 30 days after study completion, an average of 1year and 4 months.

Collaborators and Investigators

• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Collaborators: Bayer

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: June 18, 2026
• First Submitted That Met QC Criteria: June 24, 2026
• First Posted (Actual): July 1, 2026

Study Record Updates

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

More Information

Terms related to this study

• 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; Prostatic Neoplasms; Pluvicto
• Other Study ID Numbers: 23232

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