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.
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
At least two lines of treatment
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
Sequential
Anti-STEAP1 CAR T-cells
Biological/VaccineGiven IV
Biopsy Procedure
Procedure/SurgeryUndergo tumor biopsy
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Bone Scan
Procedure/SurgeryUndergo NM bone scan
Computed Tomography
Procedure/SurgeryUndergo CT scan
Cyclophosphamide
DrugGiven IV
Echocardiography Test
Procedure/SurgeryUndergo ECHO
Enzalutamide
DrugGiven PO
Fludarabine
DrugGiven IV
Leukapheresis
Procedure/SurgeryUndergo leukapheresis
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Multigated Acquisition Scan
Procedure/SurgeryUndergo MUGA
Positron Emission Tomography
Procedure/SurgeryUndergo PET scan
Incidence of grade 3 or higher treatment related unexpected 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.
Incidence of AEs (Phase II)
Toxicity will be graded according to NCI CTCAE v 5.0.
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.
Progression free survival (PFS)
PFS will be estimated using the method of Kaplan and Meier with time zero being the time of first T cell infusion.
Frequency of participants that achieve an overall response rate (ORR, including complete and partial response) according to RECIST v.1.1 or PCWG3
To measure how well the treatment succeeds in producing the desired effect.
ORR by immune RECIST
Frequency of participants that achieve a stable disease (SD) according to RECIST v.1.1 or PCWG3
To measure how well the treatment succeeds in producing the desired effect.
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Fred Hutchinson Cancer Center
Lead sponsor
PromiCell Therapeutics, Inc.
Collaborator
National Cancer Institute (NCI)
Collaborator
