Pluvicto for the Treatment of African American Men With Metastatic Castration-Resistant Prostate Cancer (PluvEquity)

A Phase II Study to Validate the Efficacy and Safety of Pluvicto in African American Men With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

This phase II trial tests how well Pluvicto works in treating African American patients with prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and that has continued to grow and spread despite the surgical removal of the testes or medical intervention to block androgen production (castration-resistant). Pluvicto is a targeted radioligand therapy. It works like a guided missile, combining tumor seeking molecules with a radioactive isotope. It circulates through the bloodstream, binds to a protein on prostate cancer cells called prostate specific membrane antigen, and destroys them using radiation. Pluvicto is approved by the Food and Drug Administration for the treatment of metastatic castration-resistant prostate cancer. This trial may help researchers determine the safety and efficacy of Pluvicto specifically in African American patients with metastatic castration-resistant prostate cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Stage IVB Prostate Cancer AJCC v8; Metastatic Castration-Resistant Prostate Adenocarcinoma
• Intervention / Treatment: Procedure: Computed Tomography; Other: Questionnaire Administration; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Bone Scan; Drug: Lutetium Lu 177 Vipivotide Tetraxetan; Procedure: Single Photon Emission Computed Tomography; Procedure: PSMA PET Scan

Detailed Description

PRIMARY OBJECTIVE:

I. To establish the clinical efficacy of lutetium Lu 177 vipivotide tetraxetan (Pluvicto) in African American (AA) men with metastatic castration-resistant prostate cancer (mCRPC) who have progressed on one androgen receptor pathway inhibitor (ARPI) and have not been treated with taxane chemotherapy for mCRPC.

SECONDARY OBJECTIVES:

I. To establish in AA men with mCRPC who have progressed on one androgen receptor (AR) pathway inhibitor and have not been treated with taxane chemotherapy for mCRPC the:

Ia. Safety and tolerability of Pluvicto; Ib. Overall survival following treatment with Pluvicto; Ic. Objective radiographic response rate to Pluvicto; Id. Prostate specific antigen (PSA) response rate to Pluvicto; Ie. Impact of Pluvicto on quality of life.

TERTIARY/EXPLORATORY OBJECTIVES:

I. Identify tumor genomic and transcriptional profiles that are associated with response to Pluvicto in AA men.

II. Identify circulating tumor deoxyribonucleic acid (DNA) molecular features that are associated with response to Pluvicto in AA men.

III. Evaluate the association of genetic ancestry with response to Pluvicto in AA men.

OUTLINE:

Patients receive Pluvicto intravenously (IV) on day 1 of each cycle. Cycles repeat every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo prostate specific membrane antigen (PSMA) positron emission tomography (PET), computed tomography (CT), bone scan, single photon emission computed tomography (SPECT), collection of blood samples, and optional biopsy throughout the trial.

After completion of study treatment, patients are followed up every 3 months for up to 36 months.

• Study Type: Interventional
• Enrollment (Estimated): 88
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Wilena Session; Phone Number: 404-778-3448; Email: wsessio@emory.edu

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital/Winship Cancer Institute
      • Contact: Jacob E. Berchuck, MD; Phone Number: 404-778-1900; Email: jberchuck@emory.edu
      • Principal Investigator: Jacob E. Berchuck, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Participants must have the ability to understand and sign an approved informed consent form (ICF) prior to participation in any study procedures

• Participants must have the ability to understand and comply with all protocol requirements

• Participants must have the ability to understand and comply with institutional radiation safety requirements

• Participants must be ≥ 18 years of age

• Participants must self-identify as being African-American

• Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

• Participants must have histological pathological, and/or cytological confirmation of adenocarcinoma of the prostate

• Participants have PSMA-positive disease on PSMA scan

• Participants must have a castrate level of serum/plasma testosterone (< 50 ng/dL or < 1.7 nmol/L)

• Participants must have progressed only once on prior second generation androgen receptor-directed therapy (ARDT) (abiraterone, enzalutamide, darolutamide, or apalutamide)

  • First generation androgen receptor inhibitor therapy (e.g. bicalutamide) is allowed but not considered as prior ARDT therapy
  • Second generation ARDT must be the most recent therapy received

• Participants must have progressive mCRPC. Documented progressive mCRPC will be based on at least 1 of the following criteria:

  • Serum/plasma PSA progression defined as 2 increases in PSA measured at least 1 week apart. The minimal start value is 2.0 ng/mL; 1.0 ng/mL is the minimal starting value if confirmed rise in PSA is the only indication of progression
  • Soft-tissue progression defined (Prostate Cancer Working Group Scher Prostate Cancer 2016 Oncology Response Criteria [PCWG3]-modified Response Evaluation Criteria in Solid Tumors [RECIST] version [v]1.1 [Eisenhauer et al 2009, Scher et al 2016])
  • Progression of bone disease: two new lesions; only positivity on the bone scan defines metastatic disease to bone (PCWG3 criteria [Scher et al 2016])

• Participants must have ≥ 1 metastatic lesion that is present on screening/baseline CT, MRI, or bone scan imaging obtained ≤ 28 days prior to randomization

• Participants must have recovered to ≤ grade 2 from all clinically significant toxicities related to prior therapies (i.e. prior chemotherapy, radiation, etc.) except alopecia

• Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L

• Platelets ≥ 100 x 10^9/L

• Hemoglobin ≥ 9 g/dL

• Total bilirubin < 2 x the institutional upper limit of normal (ULN). For participants with known Gilbert's syndrome ≤ 3 x ULN is permitted

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 3.0 x ULN OR ≤ 5.0 x ULN for participants with liver metastases

• Estimate glomerular filtration rate (eGFR) ≥ 50 mL/min/1.73m^2 using the Modification of Diet in Renal Disease (MDRD) equation

• Albumin ≥ 2.5 g/dL

• Candidates for change in ARDT as assessed by the treating physician

  • Participants cannot have previously progressed nor had intolerable toxicity to both enzalutamide and abiraterone

Exclusion Criteria:

• Previous treatment with any of the following within 6 months of enrollment: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation

• Previous PSMA-targeted radioligand therapy is not allowed

• Prior treatment with cytotoxic chemotherapy for castration resistant or castrate sensitive prostate cancer (e.g., taxanes, platinum, estramustine, vincristine, methotrexate, etc.), immunotherapy or biological therapy (including monoclonal antibodies). (Note: Taxane exposure [maximum 6 cycles] in the adjuvant or neoadjuvant setting is allowed if 12 months have elapsed since completion of this adjuvant or neoadjuvant therapy. Prior treatment with sipuleucel-T is allowed)

• Any investigational agents within 28 days prior to day of randomization

• Known hypersensitivity to any of the study treatments or its excipients or to drugs of similar classes

• Concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor, biological therapy, or investigational therapy

• Transfusion or use of bone marrow stimulating agents for the sole purpose of making a subject eligible for study inclusion

• Participants with a history of central nervous system (CNS) metastases who are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity. Participants with CNS metastases are eligible if received therapy (surgery, radiotherapy, gamma knife), asymptomatic and neurologically stable without corticosteroids. Participants with epidural disease, canal disease and prior cord involvement are eligible if those areas have been treated, are stable, and not neurologically impaired

• A superscan as seen in the baseline bone scan, defined as 99mTc bone scintigraphy pattern demonstrating diffuse, confluent, and intense radiotracer uptake throughout the majority of the axial and appendicular skeleton, with markedly reduced or absent renal visualization and minimal soft tissue activity

• Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression

• History or current diagnosis of the following electrocardiography (ECG) abnormalities indicating significant risk of safety for study participants:

  • Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third degree AV block)
  • History of familial long QT syndrome or known family history of Torsades de Pointe
  • Cardiac or cardiac repolarization abnormality, including any of the following: history of myocardial infarction (MI), angina pectoris, or coronary artery bypass graft (CABG) within 6 months prior to starting study treatment

• Concurrent serious (as determined by the principal investigator) medical conditions, including, but not limited to New York Heart Association class III or IV congestive heart failure, history of congenital prolonged QT syndrome, uncontrolled infection, known active hepatitis B or C or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation

  • HIV-infected participants who are at a low risk of AIDS-related outcomes may participate in this trial
  • Participants with an active documented coronavirus disease 2019 (COVID-19) infection (any grade of disease severity) at time of informed consent may be included only when completely recovered (in accordance with local guidance)

• Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. Participants with a prior history of malignancy that has been adequately treated and who have been disease free and treatment free for more than 3 years prior to randomization are eligible, as are participants with adequately treated non-melanoma skin cancer and superficial bladder cancer

• Sexually active males unwilling to use a condom during intercourse while taking study treatment and for 14 weeks after stopping study treatment. A condom is required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of study treatment via seminal fluid to their partner. In addition, male participants must not donate sperm for the time period specified above. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF

• Unmanageable concurrent bladder outflow obstruction or urinary incontinence. Note: Participants with bladder outflow obstruction or urinary incontinence, which is manageable and controlled with best available standard of care (including [incl.] pads, drainage) are allowed

• History of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study

• Any condition that precludes raised arms position

• Eligible for treatments other than ARDT based on presence of any mutations or biomarkers that are known as predictors of better response (e.g., AR-V7 or BRCA)

• Not able to understand and to comply with study instructions and requirements

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: Treatment (Pluvicto); Patients receive Pluvicto IV on day 1 of each cycle. Cycles repeat every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo PSMA PET scan, CT scan, bone scan, collection of blood samples, and optional SPECT scans and pre- and post-treatment biopsies.

Procedure: Computed Tomography; Undergo CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Diagnostic CAT Scan; Diagnostic CAT Scan Service Type; Other: Questionnaire Administration; Ancillary studies; Procedure: Biopsy Procedure; Undergo biopsy; Other Names: Bx; BIOPSY_TYPE; Biopsy; Procedure: Biospecimen Collection; Undergo collection of blood samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Sample Collection; Procedure: Bone Scan; Undergo bone scan; Other Names: Bone Scintigraphy; Drug: Lutetium Lu 177 Vipivotide Tetraxetan; Given IV; Other Names: 177Lu-labeled PSMA-617; 177Lu-PSMA-617; Pluvicto; Lu177-PSMA-617; Lutetium-177-PSMA-617; AAA 617; AAA-617; AAA617; Lutetium Lu 177-PSMA-617; LUTETIUM LU-177 VIPIVOTIDE TETRAXETAN; Procedure: Single Photon Emission Computed Tomography; Undergo SPECT; Other Names: ST; Medical Imaging, Single Photon Emission Computed Tomography; Single Photon Emission Tomography; single-photon emission computed tomography; SPECT; SPECT imaging; SPECT SCAN; SPET; tomography, emission computed, single photon; Tomography, Emission-Computed, Single-Photon; Single-Photon Emission Computed; Procedure: PSMA PET Scan; Undergo PSMA PET scan; Other Names: PSMA PET; Prostate-specific Membrane Antigen PET; PSMA-Positron emission tomography

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic progression-free survival (rPFS)	Will be estimated using the Kaplan-Meier method, and a 95% confidence interval for median rPFS will be estimated using the Brookmeyer-Crowley approach.	From the start of study treatment to the first objective documentation of radiographic disease progression or death, assessed up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Frequencies and percentages will be used to summarize safety events. Toxicities will be tabulated by grade, association, and cycle number.	Up to 36 months
Overall survival	Will be estimated using the Kaplan-Meier method, and a 95% confidence interval for median overall survival will be estimated using the Brookmeyer-Crowley approach.	From the start of study treatment to the date of death, assessed up to 36 months
Objective response rate	ORR is defined as the proportion of subjects achieving a best overall response of complete response (CR) or partial response (PR). Will be summarized with a 2-sided 95% confidence interval using the Clopper-Pearson method.	Up to 36 months
Disease control rate (DCR)	DCR is defined as the proportion of subjects achieving a best overall response of CR, PR, or stable disease.	Up to 36 months
Prostate specific antigen (PSA) response rate	Will be defined as the proportion of subjects achieving a ≥ 50% decline (PSA50) or ≥ 90% decline (PSA90) in PSA from baseline, confirmed per Prostate Cancer Working Group Scher Prostate Cancer 2016 Oncology Response criteria. PSA50 and PSA90 will be summarized with 2-sided 95% confidence intervals using the Clopper-Pearson method.	Up to 36 months
Health related quality of life (FACT-P)	Will be quantified through patient-reported outcome instruments administered during study participation using the Functional Assessment of Cancer Therapy-Prostate (FACT-P). Descriptive statistics such as mean, median, interquartile range, and min/max will be reported for continuous variables, and frequencies and percentages will be reported for categorical variables.	Up to 36 months
Health related quality of life (FACT-RNT)	Will be quantified through patient-reported outcome instruments administered during study participation using the Functional Assessment of Cancer Therapy-Radionuclide Therapy (FACT-RNT). Descriptive statistics such as mean, median, interquartile range, and min/max will be reported for continuous variables, and frequencies and percentages will be reported for categorical variables.	Up to 36 months

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: National Cancer Institute (NCI); Novartis
• Investigators: Principal Investigator: Jacob E Berchuck, MD, Emory University Hospital/Winship Cancer Institute

Study record dates

Study Major Dates

• Study Start (Estimated): November 2, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: September 25, 2026
• First Submitted That Met QC Criteria: September 30, 2026
• First Posted (Actual): October 6, 2026

Study Record Updates

• Last Update Posted (Actual): October 6, 2026
• Last Update Submitted That Met QC Criteria: September 30, 2026
• Last Verified: September 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; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Cytological Techniques; Cytodiagnosis; Physical Phenomena; Hydrolases; Enzymes; Enzymes and Coenzymes; Diagnostic Techniques, Surgical; Electromagnetic Phenomena; Magnetic Phenomena; Electromagnetic Radiation; Radiation; Radiation, Ionizing; Elementary Particles; Light; Optical Phenomena; Radiation, Nonionizing; Peptide Hydrolases; Metalloproteases; Carboxypeptidases; Exopeptidases; Metalloexopeptidases; Pluvicto; Biopsy; Specimen Handling; X-Rays; Photons; Glutamate Carboxypeptidase II
• Other Study ID Numbers: 2026P000169; P30CA138292 (U.S. NIH Grant/Contract); NCI-2026-06345 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); WINSHIP6884-26 (Other Identifier: Emory University Hospital/Winship Cancer Institute); 2026P000169 (Other Identifier: Emory University Hospital/Winship Cancer Institute)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No