177Lu-PSMA-617 With Liver Directed Therapy in Metastatic Castration Resistant Prostate Cancer

NCT07145177 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 25929NCI-2025-05994
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, single arm, phase 1b study to determine the safety of combining sequential Prostate-Specific Membrane Antigen (PSMA)-targeted 177Lu-PSMA-617 radionuclide therapy with liver-directed therapy in metastatic castrate-resistant prostate cancer (mCRPC) patients with liver metastases amenable to liver-directed therapy who have progressed on at least one prior androgen pathway inhibitor.

Conditions

Metastatic Prostate Cancer; Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• Percentage of participants with treatment emergent adverse events.

  Treatment emergent adverse events will be classified according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Adverse events and clinically significant laboratory abnormalities (meeting Grade 3, 4, or 5 criteria according to CTCAE) will be summarized by maximum intensity and relationship to Lu-PSMA-617 and liver-directed therapy (if applicable). Descriptive statistics will be utilized to display the data on toxicity seen. Descriptive summaries of discrete data will present the number of study participants and the incidence as a frequency and a percentage.

  up to 12 months

• Objective response Rate (ORR)

  ORR is defined as the proportion of treated participants who obtained an radiographic objective response \[confirmed complete response (CR) or confirmed partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Proportion and 95% confidence interval will be reported.

  up to 12 months

Secondary Outcomes (7)

• Median radiographic Progression-free survival (rPFS)

  up to 12 months

• Median Overall Survival (OS)

  up to 5 years

• Median duration of objective response (mDOR)

  up to 12 months

• Hepatic disease response rate (HDRR)

  up to 12 months

• Hepatic disease control rate (HDCR)

  6 months

Study Arms (1)

Treatment (177Lu-PSMA-617)

EXPERIMENTAL

Participants with diffusely PSMA-avid disease will receive standard doses of both 177Lu-PSMA-617 (7.4 Gigabequerel (GBq) every 6 weeks for up to 6 cycles) and transarterial chemoembolization (TACE) and/or ablation. Participants with one or more PSMA-negative liver lesions and PSMA-avid disease at all other sites will be treated with a single session of liver-directed therapy (either TACE or ablation) prior to initiation of 177Lu-PSMA-617 treatment. After cycle 2 of 177Lu-PSMA-617, participants who have extrahepatic stable disease/response but hepatic stable disease or progression per RECIST v1.1 will undergo liver-directed therapy. If clinically indicated and extrahepatic disease remains stable after cycle 3 of 177Lu-PSMA-617, participants may undergo a second course of liver-directed therapy. Participants will continue on study until progressive disease, study completion, unacceptable toxicity, or death.

Drug: 177Lu-PSMA-617; Procedure: Ablation; Procedure: Trans-arterial chemoembolization (TACE); Procedure: Positron Emission Tomography (PET)/Computerized tomography (CT); Procedure: Tumor Biopsy; Other: Questionnaire

Interventions

177Lu-PSMA-617 DRUG

Given intravenously (IV)

Also known as: Lutetium-177 (177Lu)-PSMA-617

Treatment (177Lu-PSMA-617)

Ablation PROCEDURE

Undergo ablation

Also known as: surgical ablation

Treatment (177Lu-PSMA-617)

Trans-arterial chemoembolization (TACE) PROCEDURE

Undergo TACE

Also known as: TACE

Treatment (177Lu-PSMA-617)

Positron Emission Tomography (PET)/Computerized tomography (CT) PROCEDURE

Undergo imaging

Also known as: PET/CT

Treatment (177Lu-PSMA-617)

Tumor Biopsy PROCEDURE

Undergo biopsy

Also known as: Biopsy

Treatment (177Lu-PSMA-617)

Questionnaire OTHER

Participant will complete questionnaire

Also known as: Quality of life questionnaire

Treatment (177Lu-PSMA-617)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed prostate cancer.
• Progressive disease by PCWG3 criteria at study entry.
• Male participants who are at least 18 years of age on the day of signing informed consent.
• Castrate level of serum testosterone at study entry (\< 50 ng/dL). Note: Participants without prior bilateral orchiectomy are required to remain on Luteinizing hormone-releasing hormone (LHRH) analogue treatment for duration of study treatment.
• Prior progression on at least one second generation androgen signaling inhibitor including abiraterone, apalutamide, darolutamide, and/or enzalutamide.
• Adverse events related to prior anti-cancer treatment (excluding LHRH analogs) must have recovered to Grade ≤ 1 (except for any grade alopecia and grade ≤ 2 neuropathy).
• Prior external beam radiotherapy is allowed if the last radiotherapy treatment was greater than 2 weeks from start of study treatment on Cycle 1 Day 1 (C1D1). Note: Participants must have recovered from all radiation-related toxicities. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
• At least one PSMA-avid extrahepatic lesion on screening PSMA Positron Emission Tomography (PET). A positive lesion is defined as uptake above background liver. Hepatic lesions may be PSMA PETnegative or positive.
• Availability of archival mCRPC tissue, or presence of a metastatic lesion that is amenable to fresh biopsy and willingness to undergo biopsy during screening if no archival mCRPC tissue available.
• The presence of one or more liver metastases amenable to liver-directed therapy in the judgment of the treating interventional radiologist. Liver metastases may be detected by CT or magnetic resonance imaging (MRI), and biopsy confirmation is not required.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 or Karnofsky ≥ 50%.
• Demonstrates adequate organ function as defined below:
• Absolute neutrophil count ≥ 1,500/ microliter (mcL).
• Platelets ≥ 100,000/mcL.
• Hemoglobin \> 9.0 g/dL.

You may not qualify if:

• De novo small cell neuroendocrine prostate cancer.
• One or more extrahepatic soft tissue lesions (lymph nodes \> 1.5 cm in short axis, visceral/soft tissue lesions \> 1 cm) on screening CT that is negative on PSMA PET. Non- PSMA avid liver lesions are allowed.
• Recipient of other systemic anti-cancer therapies administered within 14 days, or 5 half lives, whichever is shorter, prior to initiation of study treatment. Note: LHRH analogues are the exception and are permitted
• Recipient of prior PSMA-directed radioligand treatment.
• Recipient of \> 2 lines of prior taxane-based chemotherapy administered in the castration-resistant setting. Prior taxane in the castration sensitive setting does not count towards this limit. If platinum chemotherapy is added to taxane this does not count as a separate line of treatment.
• Previous bilio-enteric anastomosis, ampulla of Vater sphincterotomy, biliary stent, or biliary drain passing through the ampulla of Vater.
• Currently participating in a study of an investigational therapeutic agent or has used an investigational device within 4 weeks prior to the first dose of study treatment on C1D1. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Clinically significant cardiovascular disease including, but not limited to:
• Uncontrolled or any New York Heart Association Class 3 or 4 congestive heart failure.
• Uncontrolled angina, history of myocardial infarction, unstable angina, or stroke within 6 months before study entry.
• Major surgery within 28 days of study treatment. Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment on C1D1. Minor procedures (e.g., biopsy, cataract surgery, stent placement, endoscopy) are not considered major surgery.
• Has a secondary malignancy requiring active treatment at study entry (except for carcinoma-in-situ, non-muscle invasive bladder cancer, and non-melanoma skin cancer).
• Has an active infection requiring intravenous antibiotics within 7 days prior to C1D1.
• Has a known history of Hepatitis B infection (Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus infection (HCV RNA \[qualitative\] detected, with the following exceptions:
• Participants who are HbsAg positive are eligible if they have received hepatitis B Virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to study entry.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Novartis: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Pluvicto; Lutetium-177; Magnetic Resonance Spectroscopy; Biopsy; Surveys and Questionnaires

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Data Collection; Epidemiologic Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Rahul Aggarwal, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maya Aslam

CONTACT

(415) 514-8987; Maya.Aslam@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2025
• First Posted: August 28, 2025
• Study Start: March 16, 2026
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): October 31, 2030
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)