RecruitingPhase 1NCT06895811

Clinical Study of Safety and Efficacy of Universal PSMA CAR- T in Refractory CRPC

The Safety and Efficacy Evaluation of Universal PSMA Chimeric Antigen Receptor T Cells in the Treatment of Refractory Castration Resistant Prostate Cancer

Sponsor

Shanghai Changzheng Hospital

Enrollment

3 participants

Start Date

Mar 27, 2025

Study Type

INTERVENTIONAL

Conditions

Metastatic Prostate Cancer Metastatic Castration-resistant Prostate Cancer Castration-resistant Prostate Cancer

Summary

This is a single-arm, single-center, open-label clinical trial designed to evaluate the clinical safety and tolerability of different doses of Prostate-Specific Membrane Antigen (PSMA)-Universal Chimeric Antigen Receptor (UCAR) T-lymphocytes (PSMA-UCAR T) for the treatment of patients with refractory castration-resistant prostate cancer (CRPC).

Eligibility

Sex: MALEMin Age: 18 YearsMax Age: 80 Years

Inclusion Criteria9

Fully understood and voluntarily signed informed consent for this study;
Male, aged 18-80 years;
Expected survival of more than 6 months;
Metastatic castration-resistant prostate adenocarcinoma (CRPC) patients:
Have received CRPC standard treatment (such as novel hormone therapies, chemotherapy and radium-223, etc., one or more of the combination therapy) after the diagnosis of CRPC, and is ineffective or progressive :PSA continued rising for 3 months, or bone scan/whole-body MRI/PET-CT showed local recurrence or new metastatic lesions, demonstrating disease progression;
PSMA expression in tumor cells was positive in immunohistochemical staining of prostate/metastatic biopsy tissue before enrollment (within 6 months prior to enrollment);
ECOG score \< 2 ;
Virological examination HAV (hepatitis A virus), HBV (hepatitis B virus), HCV (hepatitis C virus), HIV (human immunodeficiency virus), TP (Treponema pallidum) quantitative detection was negative, (antigen and antibody screening method unknown, confirmed by nucleic acid method);
Hematological parameters met the following criteria: a. hemoglobin \> 100 g/L; b. platelet count \> 100 × 10\^9/L; c. neutrophils \> 1.5 × 10\^9/L.

Exclusion Criteria11

Have received any previous treatment with CAR-T therapy ;
Have received any previous treatment that targets PSMA;
Tumor pathology suggests a special type of prostate cancer (e.g., neuroendocrine prostate cancer, etc.)
Severe mental disorders;
Suffered from previous malignancies, except for the following: a. basal cell carcinoma or squamous cell carcinoma after standardized treatment; b. having a primary malignancy, but completely resected, with a complete remission time of ≥ 5 years.
Subjects with severe cardiovascular disease; a.New York Heart Association (NYHA) stage III or IV congestive heart failure; b.Myocardial infarction ≤ 6 months prior to enrollment or coronary artery bypass graft (CABG); c.Clinically significant ventricular arrhythmia, or history of unexplained syncope, nonvasovagal or not due to dehydration; d.History of severe non-ischemic cardiomyopathy; e.Decreased left ventricular ejection fraction (LVEF \< 55%) as assessed by echocardiogram or multigated acquisition (MUGA) scan, abnormal interventricular septal thickness and atrioventricular size associated with myocardial amyloidosis;
Active infectious disease or any major infectious event requiring high grade antibiotics;
Organ function in the following abnormalities: a. serum aspartate aminotransferase or alanine aminotransferase \> 2.5\*Upper Limit of Normal (ULN); CK \> ULN; CK-MB \> ULN; TnT \> 1.5\*ULN; b. total bilirubin \> 1.5\*ULN; c. partial prothrombin time or activated partial thromboplastin time or international normalized ratio \> 1.5\*ULN in the absence of anticoagulant therapy;
Participation in other clinical studies in the past three months or previous treatment with any gene therapy product;
Intolerance or hypersensitivity to cyclophosphamide or fludarabine chemotherapy;
Unsuitability to participate in this clinical study in the opinion of the investigator.

Interventions

BIOLOGICALPSMA-UCAR T (BRL-302)

Three patients will be firstly enrolled at a dose level (DL) of 5.0 × 10\^6cells/kg in the DL1 group, following lymphodepleting chemotherapy which will be given under instruction of protocol and investigators' assessment; Based on preliminary safety data, efficacy information, and PK/PD parameters obtained at DL1 cohort, the investigator may enroll another three patients in a decreased dose level group of DL-2: 3 × 10\^6 cells/kg or DL-1:1 × 10\^6 cells/ kg, after thorough discussions between the investigators.