Cell Therapy (STEAP1 CART) With Enzalutamide for the Treatment of Patients With Metastatic Castration-Resistant Prostate Cancer

NCT ID: NCT06236139

Last Updated: 2025-08-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-11-26

Study Completion Date

2027-03-30

Brief Summary

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This phase I/II trial tests the safety and effectiveness of cell therapy (STEAP1 CART) with enzalutamide in treating patients with prostate cancer that continues to grow despite surgical or medical treatments to block androgen production (castration-resistant) and that has spread from where it first started (the prostate) to other places in the body (metastatic). Prostate cancer is the second leading cause of cancer deaths in men. Localized prostate cancer is often curable and even metastatic disease may respond to treatment for a few years. Despite multiple therapies, including hormone therapy and chemotherapy, metastatic castration-resistant prostate cancer (mCRPC) still remains an incurable disease. Recently, adoptive cellular immunotherapies have been developed to transfer immunogenic cells to the patient to produce an anti-tumor response. Chimeric antigen receptor T (CART)-cell therapy is a type of treatment in which a patient's T-cells (a type of immune cell) are changed in the laboratory so they will attack tumor cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's tumor cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Prostate stem cell antigen and prostate specific membrane antigen CAR T cell therapies have been shown to be safe and effective, but objective tumor responses remain rare. STEAP1 is an antigen that promotes cancer growth and spread and is found to be broadly expressed in mCRPC tissues. STEAP1 CART is CAR T cells that have been engineered with a STEAP1 antigen to better target prostate tumor cells. Enzalutamide is in a class of medications called androgen receptor inhibitors. It works by blocking the effects of androgen (a male reproductive hormone) to stop the growth and spread of cancer cells. Giving STEAP1 CART with enzalutamide may kill more tumor cells in patients with mCRPC.

Detailed Description

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OUTLINE: This is a dose escalation study of STEAP1 CART in combination with enzalutamide followed by a dose expansion study.

Patients undergo leukapheresis then receive cyclophosphamide intravenously (IV) and fludarabine IV on days -5, -4 and -3 and STEAP1 CART IV on day 0. Patients may receive enzalutamide orally (PO) on day 0 then once daily (QD) in the absence of disease progression or unacceptable toxicity. Patients also undergo a tumor biopsy at baseline, day 14 and optionally at progression. Patients additionally undergo blood sample collection, nuclear medicine (NM) bone scan and computed tomography (CT) scan, or magnetic resonance imaging (MRI) or positron emission tomography (PET) scan throughout study. Additionally, patients may undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) at screening.

After completion of study treatment, patients are followed up at 2, 3, 4, 5, 6, 9, and 12 months then every 6 months up to year 5 followed by yearly up to year 15.

Conditions

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

Study Design

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Allocation Method

NA

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (STEAP1 CART, enzalutamide)

Patients undergo leukapheresis then receive cyclophosphamide IV and fludarabine IV on days -5, -4 and -3 and STEAP1 CART IV on day 0. Patients may receive enzalutamide PO on day 0 then QD in the absence of disease progression or unacceptable toxicity. Patients also undergo a tumor biopsy at baseline, day 14 and optionally at progression. Patients additionally undergo blood sample collection, NM bone scan and CT scan, or MRI or PET scan throughout study. Additionally, patients may undergo ECHO or MUGA at screening.

Group Type EXPERIMENTAL

Anti-STEAP1 CAR T-cells

Intervention Type BIOLOGICAL

Given IV

Biopsy

Intervention Type PROCEDURE

Undergo tumor biopsy

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Bone Scan

Intervention Type PROCEDURE

Undergo NM bone scan

Computed Tomography

Intervention Type PROCEDURE

Undergo CT scan

Cyclophosphamide

Intervention Type DRUG

Given IV

Echocardiography

Intervention Type PROCEDURE

Undergo ECHO

Enzalutamide

Intervention Type DRUG

Given PO

Fludarabine

Intervention Type DRUG

Given IV

Leukapheresis

Intervention Type PROCEDURE

Undergo leukapheresis

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Multigated Acquisition Scan

Intervention Type PROCEDURE

Undergo MUGA

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET scan

Interventions

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Anti-STEAP1 CAR T-cells

Given IV

Intervention Type BIOLOGICAL

Biopsy

Undergo tumor biopsy

Intervention Type PROCEDURE

Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Bone Scan

Undergo NM bone scan

Intervention Type PROCEDURE

Computed Tomography

Undergo CT scan

Intervention Type PROCEDURE

Cyclophosphamide

Given IV

Intervention Type DRUG

Echocardiography

Undergo ECHO

Intervention Type PROCEDURE

Enzalutamide

Given PO

Intervention Type DRUG

Fludarabine

Given IV

Intervention Type DRUG

Leukapheresis

Undergo leukapheresis

Intervention Type PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Multigated Acquisition Scan

Undergo MUGA

Intervention Type PROCEDURE

Positron Emission Tomography

Undergo PET scan

Intervention Type PROCEDURE

Other Intervention Names

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Anti-STEAP1 CAR T Cells Anti-STEAP1 CAR-T Cells STEAP1 CAR-T Cells STEAP1-targeting CAR T-cells BIOPSY_TYPE Bx Biological Sample Collection Biospecimen Collected Specimen Collection Bone Scintigraphy CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography CT CT Scan tomography (-)-Cyclophosphamide 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate Asta B 518 B-518 Carloxan Ciclofosfamida Ciclofosfamide Cicloxal Clafen Claphene CP monohydrate CTX CYCLO-cell Cycloblastin Cycloblastine Cyclophospham Cyclophosphamid monohydrate Cyclophosphamide Monohydrate Cyclophosphamidum Cyclophosphan Cyclophosphane Cyclophosphanum Cyclostin Cyclostine Cytophosphan Cytophosphane Cytoxan Fosfaseron Genoxal Genuxal Ledoxina Mitoxan Neosar Revimmune Syklofosfamid WR- 138719 WR-138719 EC ASP9785 MDV3100 Xtandi Fluradosa Leukocytopheresis Therapeutic Leukopheresis Leukocyte Adsorptive Apheresis White Blood Cell Reduction Apheresis Magnetic Resonance 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 Blood Pool Scan Equilibrium Radionuclide Angiography Gated Blood Pool Imaging Gated Heart Pool Scan MUGA MUGA Scan Multi-Gated Acquisition Scan Radionuclide Ventriculogram Scan Radionuclide Ventriculography RNVG SYMA Scanning Synchronized Multigated Acquisition Scanning RNV Scan Medical Imaging, Positron Emission Tomography PET PET Scan Positron emission tomography (procedure) Positron Emission Tomography Scan Positron-Emission Tomography proton magnetic resonance spectroscopic imaging PT

Eligibility Criteria

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Inclusion Criteria

* Tissue confirmation of prostate adenocarcinoma
* Measurable disease by RECIST 1.1 criteria or bone only metastases with measurable PSA ( ≥ 1 ng/mL)
* Must have progressed (at least 2 rising PSA levels with at least a 1-week interval and a minimum PSA of 1.0 ng/mL, progression per RECIST 1.1, or 2 or more new bone lesions by bone scan), after becoming castration-resistant
* Have received the following for metastatic prostate cancer:

* At least two lines of treatment
* At least two Food and Drug Administration (FDA)-approved therapies with at least one being a second generation androgen receptor signaling inhibitor (e.g., abiraterone, darolutamide, apalutamide, or enzalutamide)
* All available targeted therapies for which they are eligible in the metastatic setting (e.g., PARP inhibitors for BRCA 1/2 and immune checkpoint inhibitor for MSI-H or TMB-H ≥ 10 mut/Mb)
* Castrate levels of testosterone (\< 50 ng/dL) with or without the use of androgen deprivation therapy
* 18 years or older at the time of enrollment
* Capable of understanding and providing a written informed consent
* Fertile male participants and their female partners must be willing to use an effective contraceptive method before, during, and for at least 4 months after the STEAP1 CART cell infusion
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Participants will be permitted to receive radiation therapy for palliative purposes throughout the study period, except during the 2-week period prior to undergoing leukapheresis
* Serum creatinine =\< 1.5 x upper limit of normal (ULN) or estimated creatinine clearance \> 50 mL/min as calculated using the Cockcroft-Gault formula and not dialysis dependent
* Total bilirubin ≤ 1.5 x ULN. Participants with suspected Gilbert syndrome may be included if Total bilirubin (Bili) \> 3 mg/dL but no other evidence of hepatic dysfunction
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 5 x ULN
* ≤ grade 1 dyspnea and oxygen saturation (SaO2) ≥ 92% on ambient air
* If pulmonary function tests (PFTs) are performed based on the clinical judgement of the treating physician, participants with forced expiratory volume in 1 second (FEVI) \>= 50% of predicted and diffusion capacity of the lung for carbon monoxide (DLCO) (corrected) of \>= 40% of predicted will be eligible
* Participants \>= 60 years of age are required to have left ventricular ejection fraction (LVEF) evaluation performed within 1 year prior to lymphodepletion chemotherapy. LVEF may be established with echocardiogram or MUGA scan, and left ejection fraction must be \>= 35%. Cardiac evaluation for other participants is at the discretion of the treating physician
* Absolute neutrophil count (ANC) \> 1500 cells/ mm\^3
* Hemoglobin \> 9 g/dL
* Platelets \> 100,000 per mm\^3

Exclusion Criteria

* Expecting to conceive or father children for the duration of the trial through 4 months after T cell infusion
* Active autoimmune disease: Participants with active autoimmune disease requiring immunosuppressive therapy are excluded. Case by case exemptions are possible with approval by principal investigator (PI)
* Corticosteroid therapy at a dose equivalent of \>15 mg of prednisone per day (or equivalent). Pulsed corticosteroid use for disease control is acceptable
* Concurrent use of other investigational anti-cancer agents except for androgen deprivation therapy
* Active uncontrolled infection: human immunodeficiency virus (HIV) positive participants on highly active antiretroviral therapy (HAART) with a CD4 count \> 500 cells/mm\^3 are considered controlled, as are individuals with a history of hepatitis C who have successfully completed antiviral therapy with an undetectable viral load, and those with hepatitis B who have hepatitis well controlled on medication
* Uncontrolled concurrent illness: Participants may not have uncontrolled or concurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia that would limit compliance with study requirements
* Untreated brain metastases: Participants with small asymptomatic brain metastases ( \< 1 cm) or those with brain metastases previously treated and controlled with surgery or radiotherapy will be considered for inclusion at discretion of principal investigator, so long as all other eligibility criteria are met
* Active treatment for prior immune related adverse event to any immunotherapy: Participants receiving ongoing treatment for prior serious immune-related adverse events are excluded, with exception of hormone supplementation or corticosteroid therapy at equivalent of \> 15 mg prednisone (or equivalent) per day, unless otherwise approved by PI
* Significant underlying neurologic disease: Study participants must not have significant active underlying neurologic disease, unless approved by PI. Peripheral neuropathy related to diabetes or prior chemotherapy is acceptable
* Other medical, social, or psychiatric factor that interferes with medical appropriateness and/or ability to comply with study, as determined by the PI
* Known allergic reactions to any of the components of study treatments
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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PromiCell Therapeutics, Inc.

UNKNOWN

Sponsor Role collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Rosa Nadal Rios, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

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Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Fred Hutch Intake

Role: CONTACT

206-606-1024

Facility Contacts

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Fred Hutch Intake

Role: primary

206-606-1024

Other Identifiers

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NCI-2023-10316

Identifier Type: REGISTRY

Identifier Source: secondary_id

20204

Identifier Type: OTHER

Identifier Source: secondary_id

RG1123855

Identifier Type: -

Identifier Source: org_study_id

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