Recruiting
Phase 1
Phase 2

STEAP1 CART with Enzalutamide

Sponsor:

Fred Hutchinson Cancer Center

Code:

NCT06236139

Conditions

Metastatic Castration-Resistant Prostate Carcinoma

Metastatic Prostate Adenocarcinoma

Stage IVB Prostate Cancer AJCC v8

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Anti-STEAP1 CAR T-cells

Biopsy Procedure

Biospecimen Collection

Bone Scan

Computed Tomography

Study Details

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) 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

Metastatic Castration-Resistant Prostate Carcinoma

Metastatic Prostate Adenocarcinoma

Stage IVB Prostate Cancer AJCC v8

Study ID

NCT06236139

Start date

Nov 26, 2024

Status verified date

Aug, 2026

Completion date

Mar 30, 2027

Anticipated

Primary completion date

Mar 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

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 (ADT)
  • 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 ADT
  • 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
  • Participants with brain metastasis
  • 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
  • Participants with no bridging therapy options according to the treating medical oncologist. The specific bridging treatment plan must be documented in the Electronic Medical Record (EMR) by the treating medical oncologist within 2 weeks of signing informed consent

Study Design

Enrollment

48 participants

Anticipated

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 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.

Interventions

Anti-STEAP1 CAR T-cells

Given IV

Biopsy Procedure

Undergo tumor biopsy

Biospecimen Collection

Undergo blood sample collection

Bone Scan

Undergo NM bone scan

Computed Tomography

Undergo CT scan

Cyclophosphamide

Given IV

Echocardiography Test

Undergo ECHO

Enzalutamide

Given PO

Fludarabine

Given IV

Leukapheresis

Undergo leukapheresis

Magnetic Resonance Imaging

Undergo MRI

Multigated Acquisition Scan

Undergo MUGA

Positron Emission Tomography

Undergo PET scan

Primary outcome measure

  • Incidence of grade 3 or higher treatment related unexpected adverse events (AEs) (Phase I) [ Time Frame: Up to 28 days post infusion ]
  • Incidence of AEs (Phase II) [ Time Frame: Up to 28 days post infusion ]
  • Response (Phase II) [ Time Frame: Up to 1 year post infusion ]

Central Contacts and Locations

Central contacts

Fred Hutch Intake

206-606-1024hutchdoc@fredhutch.org

Locations

Fred Hutch/University of Washington Cancer Consortium

Recruiting

Seattle, Washington, United States, 98109

Contacts

Fred Hutch Intake

206-606-1024hutchdoc@fredhutch.org

Principal Investigator:

Rosa Nadal Rios, MD, PhD

More Information

Sponsor

Fred Hutchinson Cancer Center

Last update posted

Aug 11, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Fred Hutchinson Cancer Center on 2026-08-11.