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

NCT06895811 | Active Not Recruiting Phase 1

• 1 other identifier: 2022-BRL-302
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

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

Keywords

Prostate cancer; Universal CAR-T; Metastatic Castration-resistant Prostate Cancer; Chimeric Antigen Receptor T cell

Outcome Measures

Primary Outcomes (3)

• The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE V5.0)

  Safety assessment: toxicity profile

  Through 6 months after CAR T cell infusion

• Cytokine Release Syndrome (CRS) grading post CAR T cell infusion.

  Safety assessment: toxicity profile

  Through 6 months after CAR T cell infusion

• Safety assessment: dose-limiting toxicity

  Incidence of dose-limiting toxicity (DLT) within 28 days. Dose-limiting toxicity (DLT) is defined as any relevant adverse event that ≥ grade 3 and did not resolve to a grade ≤ grade 2 within 28 days after the first infusion back.

  28 days after CAR T cell infusion

Secondary Outcomes (6)

• Efficacy assessment: PSA changes

  6 months after CAR T cell infusion

• Efficacy assessment: radiographic Progression-Free Survival (rPFS)

  6 months after CAR T cell infusion

• 6-months Progression-Free Survival (PFS)

  6 months after CAR T cell infusion

• Pharmacokinetics (PK) assessment: expansion of CAR T cells

  From Day 1 till at least 3 months after CAR T cell infusion

• Pharmacokinetics (PK) assessment: persistence of CAR T cells

  From Day 1 till at least 3 months after CAR T cell infusion

Study Arms (1)

PSMA-UCAR T (BRL-302)

EXPERIMENTAL

Biological: PSMA-UCAR T (BRL-302)

Interventions

PSMA-UCAR T (BRL-302) BIOLOGICAL

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.

PSMA-UCAR T (BRL-302)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shanghai Changzheng Hospital: lead
• Bioray Laboratories: collaborator

Study Sites (1)

Changzheng hospital

Shanghai, Shanghai Municipality, 201109, China

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Shancheng Ren, MD, PhD

  Shanghai Changzheng Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Chief of Urology

Study Record Dates

• First Submitted: November 12, 2024
• First Posted: March 26, 2025
• Study Start: March 27, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: April 28, 2026

Record last verified: 2026-04

Locations

CN (1)