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

NCT ID: NCT06895811

Last Updated: 2025-04-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-03-27
• Study Completion Date: 2025-11-30

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).

Detailed Description

This is a single-arm, single-center, open-label clinical trial, which aims to evaluate safety and clinical efficacy of different doses of PSMA-UCAR T (BRL-302) in treating patients with refractory CRPC.

Three patients will be firstly enrolled at a dose level (DL) of 5.0 × 10^6cells/kg in the DL1 group. 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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PSMA-UCAR T (BRL-302)

Group Type: EXPERIMENTAL

PSMA-UCAR T (BRL-302)

Intervention Type: 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.

Interventions

PSMA-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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Fully understood and voluntarily signed informed consent for this study;

2. Male, aged 18-80 years;

3. Expected survival of more than 6 months;

4. 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;

5. PSMA expression in tumor cells was positive in immunohistochemical staining of prostate/metastatic biopsy tissue before enrollment (within 6 months prior to enrollment);

6. ECOG score < 2 ;

7. 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);

8. 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 Criteria

1. Have received any previous treatment with CAR-T therapy ;

2. Have received any previous treatment that targets PSMA;

3. Tumor pathology suggests a special type of prostate cancer (e.g., neuroendocrine prostate cancer, etc.)

4. Severe mental disorders;

5. 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.

6. 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;

7. Active infectious disease or any major infectious event requiring high grade antibiotics;

8. 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;

9. Participation in other clinical studies in the past three months or previous treatment with any gene therapy product;

10. Intolerance or hypersensitivity to cyclophosphamide or fludarabine chemotherapy;

11. Unsuitability to participate in this clinical study in the opinion of the investigator.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Bioray Laboratories

INDUSTRY

Sponsor Role: collaborator

Shanghai Changzheng Hospital

OTHER

Sponsor Role: lead

Responsible Party

Ren Shancheng

Professor, Chief of Urology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Shancheng Ren, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Shanghai Changzheng Hospital

Locations

Changzheng hospital

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Shancheng Ren, MD, PhD

Role: CONTACT

renshancheng@gmail.com

139 1779 3885

Duocai Li

Role: CONTACT

liduocai226@qq.com

18721655820

Facility Contacts

Shancheng Ren, PhD/MD

Role: primary

renshancheng@gmail.com

8613917793885

Other Identifiers

2022-BRL-302

Identifier Type: -

Identifier Source: org_study_id