177^Lu-PSMA-617 in Combination With Sipuleucel-T for the Treatment of Metastatic Castration-Resistant Prostate Cancer

NCT07219147 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 25161NCI-2025-07470P30CA033572
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial compares the effect of lutetium Lu 177 (177\^Lu)-prostate-specific membrane antigen (PSMA)-617 in combination with Sipuleucel-T to 177\^Lu-PSMA-617 alone in treating patients with prostate that has spread from where it first started (primary site) to other places in the body (metastatic) and has continued to grow and spread despite surgical or medical intervention to block androgen production (castration-resistant). 177\^Lu-PSMA-617, a type of radioconjugate, binds to a protein called PSMA, which is found on some prostate tumor cells. It gives off radiation that may kill the tumor cells. Sipuleucel-T, a type of vaccine and a type of cellular adoptive immunotherapy, is made from immune system cells. The cells are treated with a protein that is made by combining a protein found on prostate tumor cells with a growth factor. When the cells are injected back into the patient, they may stimulate T cells to kill prostate tumor cells. Giving 177\^Lu-PSMA-617 in combination with sipuleucel-T may be safe, tolerable, and/or effective compared to 177\^Lu-PSMA-617 alone in treating patients with metastatic castration-resistant prostate cancer.

Conditions

Stage IVB Prostate Cancer AJCC v8; Metastatic Castration-Resistant Prostate Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Anti-prostatic acid phosphatase (PAP) immunoglobulin G (IgG) antibody response rate

  Will be defined as the proportion of patients with an IgG titer \> 400. Comparisons between study arms will be performed using the Fisher's exact test. Descriptive statistics will be used to summarize the antibody response rates, and Clopper-Pearson exact 95% confidence intervals will be calculated.

  Between week 7 and week 19

• Change in anti-PAP IgG antibody titers

  Descriptive statistics will be used to summarize antibody titer levels at each time point. Comparisons between study arms will be performed using the Wilcoxon signed-rank test or Student's t-test, as appropriate.

  Between week 7 and week 19

Secondary Outcomes (6)

• Change in anti-PA2024 antibody titers

  Between week 7 and week 19

• Incidence of adverse events

  Up to 30 days after last dose of study treatment

• Proportion of patients achieving a ≥ 50% reduction in prostate specific antigen (PSA) levels (PSA50 response rate)

  At baseline up to 3 years

• Objective response rate

  Up to 3 years

• Radiographic progression-free survival (rPFS)

  From enrollment to progression or death from any cause, assessed up to 3 years

Study Arms (2)

Arm A (177^Lu-PSMA-617)

ACTIVE COMPARATOR

Patients receive 177\^Lu-PSMA-617 IV. Treatment repeats every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, PSMA PET/CT, bone scan, and MRI throughout the study. Additionally, patients may undergo MRI or CT of the brain throughout the study.

Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Drug: Lutetium Lu 177 Vipivotide Tetraxetan; Procedure: Magnetic Resonance Imaging; Procedure: PSMA PET Scan; Biological: Sipuleucel-T

Arm B (177^Lu-PSMA-617, sipuleucel-T)

EXPERIMENTAL

Patients receive 177\^Lu-PSMA-617 IV. Treatment repeats every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Starting during week 8 of treatment, patients receive sipuleucel-T IV over 1 hour. Treatment repeat every 2 weeks for up to 3 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo leukapheresis, blood sample collection, PSMA PET/CT, bone scan, and MRI throughout the study. Additionally, patients may undergo MRI or CT of the brain throughout the study.

Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Procedure: Leukapheresis; Drug: Lutetium Lu 177 Vipivotide Tetraxetan; Procedure: Magnetic Resonance Imaging; Procedure: PSMA PET Scan; Biological: Sipuleucel-T

Interventions

PSMA PET Scan PROCEDURE

Undergo PSMA PET/CT

Also known as: Prostate-specific Membrane Antigen PET, PSMA PET, PSMA-Positron emission tomography

Arm A (177^Lu-PSMA-617); Arm B (177^Lu-PSMA-617, sipuleucel-T)

Sipuleucel-T BIOLOGICAL

Given IV

Also known as: APC 8015, APC-8015, APC8015, APC8015 Vaccine, PA2024 (PAP/GM-CSF)-Loaded Dendritic Cell Vaccine, Provenge, SipT

Arm A (177^Lu-PSMA-617); Arm B (177^Lu-PSMA-617, sipuleucel-T)

Bone Scan PROCEDURE

Undergo bone scan

Also known as: Bone Scintigraphy

Arm A (177^Lu-PSMA-617); Arm B (177^Lu-PSMA-617, sipuleucel-T)

Computed Tomography PROCEDURE

Undergo CT and PSMA PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Arm A (177^Lu-PSMA-617); Arm B (177^Lu-PSMA-617, sipuleucel-T)

Leukapheresis PROCEDURE

Undergo leukapheresis

Also known as: Leukocyte Adsorptive Apheresis, Leukocytopheresis, Therapeutic Leukopheresis, White Blood Cell Reduction Apheresis

Arm B (177^Lu-PSMA-617, sipuleucel-T)

Lutetium Lu 177 Vipivotide Tetraxetan DRUG

Given IV

Also known as: 177Lu-labeled PSMA-617, 177Lu-PSMA-617, AAA 617, AAA-617, AAA617, Lu177-PSMA-617, Lutetium Lu 177-PSMA-617, LUTETIUM LU-177 VIPIVOTIDE TETRAXETAN, Lutetium-177-PSMA-617, Pluvicto

Arm A (177^Lu-PSMA-617); Arm B (177^Lu-PSMA-617, sipuleucel-T)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm A (177^Lu-PSMA-617); Arm B (177^Lu-PSMA-617, sipuleucel-T)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Arm A (177^Lu-PSMA-617); Arm B (177^Lu-PSMA-617, sipuleucel-T)

Eligibility Criteria

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

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• If unavailable, exceptions may be granted with study principal investigator (PI) approval
• Age: ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) ≤ 1
• Male
• Progressive castration-resistant metastatic prostate cancer with pathologically confirmed adenocarcinoma of the prostate without small cell features
• Patients must have either:
• Measurable disease
• For extranodal (visceral) lesions (e.g. lung, liver, etc.) to be considered measurable, they must be ≥ 10 mm in one dimension, using spiral CT
• For lymph nodes to be considered measurable (i.e., target or evaluable lesions), they must be ≥ 20 mm in at least one dimension, using spiral CT
• OR non-measurable disease
• All other lesions, including small lesions (longest diameter \< 20 mm with conventional techniques or \< 10 mm with spiral CT scan) and truly non-measurable lesions
• Lesions that are considered non-measurable include bone lesions (only). Progression on first generation ADT

You may not qualify if:

• Any approved or investigational anticancer therapy, including chemotherapy, hormonal therapy (e.g., androgen receptor \[AR\] antagonists, 5 alpha reductase inhibitor, estrogen), or radiotherapy, within 4 weeks prior to initiation of study treatment
• Treatment with any of the following medications or interventions within 28 days of registration:
• External beam radiation therapy or surgery
• Chrysanthemum morifolium/Ganoderma lucidum/Glycyrrhiza glabra/Isatis indigotica/Panax pseudoginseng/Rabdosia rubescens/Scutellaria baicalensis/Serona repens supplement (PC-SPES) (or PC-SPEC) or saw palmetto
• Systemic corticosteroids. Use of inhaled, intranasal, and topical steroids is acceptable
• Megestrol acetate (Megace®), diethyl stilbestrol (DES), or cyproterone acetate
• Ketoconazole
• alpha-reductase inhibitors (e.g., finasteride \[Proscar®\], dutasteride \[Avodart®\])
• High dose calcitriol (1,25\[OH\]2 vitamin \[Vit\]D) (i.e., \> 7.0 ug/week)
• Prior treatment with 177\^Lu-PSMA-617 and/or sipuleucel-T
• Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
• Treatment with any investigational vaccine within 2 years of registration or treatment with any other investigational product within 28 days of registration
• Patients with acute leukemias, accelerated/blast-phase chronic myelogenous leukemia, chronic lymphocytic leukemia, Burkitt lymphoma, plasma cell leukemia, or non-secretory myeloma
• Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Specimen Handling; Leukapheresis; Pluvicto; Magnetic Resonance Spectroscopy; Glutamate Carboxypeptidase II; sipuleucel-T

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)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Carboxypeptidases; Exopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloexopeptidases; Metalloproteases

Study Officials

• Alex Chehrazi-Raffle, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alexander Chehrazi-Raffle, MD

CONTACT

6263598111; aChehraziraffle@coh.org

Study Design

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

Study Record Dates

• First Submitted: October 17, 2025
• First Posted: October 21, 2025
• Study Start: March 6, 2026
• Primary Completion (Estimated): July 26, 2028
• Study Completion (Estimated): July 26, 2028
• Last Updated: April 20, 2026

Record last verified: 2026-04

Locations

US (1)