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

NCT06236139 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: RG1123855NCI-2023-1031620204
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (6)

• Incidence of grade 3 or higher adverse events (AEs) (Phase I)

  Toxicity will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.

  Up to 28 days post infusion

• Incidence of AEs (Phase II)

  Toxicity will be graded according to NCI CTCAE v 5.0.

  Up to 28 days post infusion

• Response (Phase II)

  Response will be defined as best overall response rate by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and/or Prostate Cancer Working Group 3 (PCWG3) criteria.

  Up to 1 year post infusion

• Prostate specific antigen (PSA) response

  PSA responses, defined as \>= 50% reductions in PSA from baseline at any point post baseline assessment will be calculated.

  At baseline up to 1 year post infusion

• Time to response (TTR)

  TTR will be assessed from the time of study infusion to time of first documented response (partial response \[PR\] or better).

  At time from study infusion to time of first documented response up to 1 year post infusion

• Duration of response (DOR)

  DOR will be assessed from the time of first documented response (PR or better) to time of confirmed disease progression.

  At time of first documented response to time of confirmed progression up to 1 year post infusion

Secondary Outcomes (6)

• Progression free survival (PFS)

  At time from initiation of protocol treatment to disease progression or death up to 1 year post infusion

• Overall survival (OS)

  At time from initiation of protocol treatment to death of any cause up to 1 year post infusion

• Frequency of participants that achieve an overall response rate (ORR, including complete and partial response) according to RECIST v.1.1 or PCWG3

  Anti-tumor response according to RECIST v1.1 or PCWG3 up to 1 year post infusion

• Frequency of participants that achieve a stable disease (SD) according to RECIST v.1.1 or PCWG3

  Anti-tumor response according to RECIST v1.1 or PCWG3 up to 1 year post infusion

• Frequency of participants that achieve a clinical benefit rate (ORR + SD) stable disease RECIST v.1.1 or PCWG3

  Anti-tumor response according to RECIST v1.1 or PCWG3 up to 1 year post infusion

Study Arms (1)

Treatment (STEAP1 CART, enzalutamide)

EXPERIMENTAL

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.

Biological: Anti-STEAP1 CAR T-cells; Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Drug: Cyclophosphamide; Procedure: Echocardiography; Drug: Enzalutamide; Drug: Fludarabine; Procedure: Leukapheresis; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan; Procedure: Positron Emission Tomography

Interventions

Computed Tomography PROCEDURE

Undergo CT scan

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

Treatment (STEAP1 CART, enzalutamide)

Enzalutamide DRUG

Given PO

Also known as: ASP9785, MDV3100, Xtandi

Treatment (STEAP1 CART, enzalutamide)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-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

Treatment (STEAP1 CART, enzalutamide)

Echocardiography PROCEDURE

Undergo ECHO

Also known as: EC

Treatment (STEAP1 CART, enzalutamide)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (STEAP1 CART, enzalutamide)

Leukapheresis PROCEDURE

Undergo leukapheresis

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

Treatment (STEAP1 CART, enzalutamide)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: 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

Treatment (STEAP1 CART, enzalutamide)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: 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

Treatment (STEAP1 CART, enzalutamide)

Positron Emission Tomography PROCEDURE

Undergo PET scan

Also known as: 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

Treatment (STEAP1 CART, enzalutamide)

Anti-STEAP1 CAR T-cells BIOLOGICAL

Given IV

Also known as: Anti-STEAP1 CAR T Cells, Anti-STEAP1 CAR-T Cells, STEAP1 CAR-T Cells, STEAP1-targeting CAR T-cells

Treatment (STEAP1 CART, enzalutamide)

Biopsy PROCEDURE

Undergo tumor biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (STEAP1 CART, enzalutamide)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

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

Treatment (STEAP1 CART, enzalutamide)

Bone Scan PROCEDURE

Undergo NM bone scan

Also known as: Bone Scintigraphy

Treatment (STEAP1 CART, enzalutamide)

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• PromiCell Therapeutics, Inc.: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Biopsy; Specimen Handling; Cyclophosphamide; enzalutamide; fludarabine; Leukapheresis; Magnetic Resonance Spectroscopy

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)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Rosa Nadal Rios, MD, PhD

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fred Hutch Intake

CONTACT

206-606-1024; hutchdoc@fredhutch.org

Study Design

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

Study Record Dates

• First Submitted: January 9, 2024
• First Posted: February 1, 2024
• Study Start: November 26, 2024
• Primary Completion (Estimated): March 30, 2027
• Study Completion (Estimated): March 30, 2027
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)