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

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

This is one center, single-arm, open-label investigator initiated trial to assess the safety and efficacy of enhanced autologous PSMA chimeric antigen receptor T cells in the treatment for patients with refractory castration resistant prostate cancer, and the sample size is set to 7-18 subjects.

Study Overview

• Status: Active, not recruiting
• Conditions: Castration-resistant Prostate Cancer; Metastatic Castration-resistant Prostate Cancer
• Intervention / Treatment: Drug: Enhanced autologous PSMA-CAR T

Detailed Description

This is one center, single-arm, open-label investigator initiated trial to assess the safety and efficacy of enhanced autologous PSMA chimeric antigen receptor T cells in the treatment for patients with refractory castration resistant prostate cancer, and the sample size is set to 7-18 subjects. Based on the "3 + 3" dose escalation design principle, subjects will be divided into 3 groups from low dose to high dose in sequence (Group A; Group B; Group C). Additional subjects will be enrolled into the RP2D group to ensure that 6-9 efficacy-evaluable subjects are available in the RP2D group before entering the phase II study.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 201109
      • Changzheng hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Fully understood and voluntarily signed informed consent for this study;
2. male, aged 18-75 years;
3. expected survival of more than 6 months;
4. metastatic castration-resistant prostate adenocarcinoma (CRPC) patients.
5. Receiving CRPC standard treatment (such as new endocrine therapy, chemotherapy and radium-223, etc., one or more of the combination therapy) after the diagnosis of CRPC, ineffective or progressive disease (PSA continued to rise for 3 months, or bone scan/whole-body MRI/PET-CT showed local recurrence or new metastatic lesions, demonstrating disease progression);
6. PSMA expression in tumor cells was positive in immunohistochemical staining of prostate/metastatic biopsy tissue before enrollment;
7. ECOG score < 2 ;
8. 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 × 109/L; c. neutrophils > 1.5 × 109/L.

Exclusion Criteria:

Subjects meeting any of the following exclusion criteria will be excluded:

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 > 2.5ULN; CK > ULN; CK-MB > ULN; TnT > 1.5ULN; b. total bilirubin > 1.5ULN; c. partial prothrombin time or activated partial thromboplastin time or international normalized ratio > 1.5ULN 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 and fludarabine chemotherapy;
11. unsuitability to participate in this clinical study in the opinion of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Enhanced autologous PSMA-CAR T: Enhanced autologous PSMA-CAR T is an electrotransfer system based on non-viral transposons that integrates the CAR gene into the genome of host cells by electrotransfer using PMSA as a target, while this CAR vector co-expresses enhanced factors and plays a strong regulatory role in innate and adaptive immunity.

Drug: Enhanced autologous PSMA-CAR T; 3 escalated dosing cohorts are designed to explore safety and efficacy of enhanced autologous PSMA-CAR T: cohort A： CART-PSMA cells 0.25×106/kgBW, following lymphodepleting chemotherapy with cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day given according to protocol; cohort B： CART-PSMA cells 0.75×106/kgBW，following lymphodepleting chemotherapy with cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day given according to protocol; cohort C： CART-PSMA cells 2×106/kgBW，following lymphodepleting chemotherapy with cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day given according to protocol;

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DLT	The number and severity of dose-limiting toxicity (DLT) events	Within 28 Days After Enhanced autologous PSMA-CAR T Infusion
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy assessment: PSA changes	Prostate-Specific Antigen (PSA) changes assessed by serum PSA measurement (ng/ml).	6 months after CAR-T cell infusion
Efficacy assessment: radiographic Progression-Free Survival (rPFS)	rPFS is defined as the time between treatment with study drug and the development of imaging progression or death from any cause, whichever occurs first, with imaging progression encompassing the evaluation of progression of primary lesions, non-regional lymph node invasion, soft tissue metastases, and bone metastatic lesions according to RECIST 1.1 and PCWG3 criteria.	3 months after CAR-T cell infusion
Pharmacokinetics (PK) assessment: expansion of CAR-T cells	With the day of the first infusion of the cellular preparation recorded as DO, the monitoring phase of the pharmacokinetic study started from 1 day before the first infusion (D-1). Expansion of CAR T cells will be assessed by concentration profile of CAR-T cells in peripheral blood after CAR-T infusion.	From Day 1 till at least 3 months after CAR-T cell infusion
Pharmacokinetics (PK) assessment: persistence of CAR T cells	With the day of the first infusion of the cellular preparation recorded as DO, the monitoring phase of the pharmacokinetic study started from 1 day before the first infusion (D-1). Persistence of CAR T cells will be assessed by T-cell survival time (area under the curve AUCO-28 at 28 days and area under the curve AUCO-90 at 90 days);	From Day 1 till at least 3 months after CAR-T cell infusion
Pharmacodynamics (PD) assessment eg. (Level of IL-6)	Pharmacokinetic (PD) endpoints is assessed by changes in serum cytokine levels (eg.IL-6) after CAR-T infusion.	From Day 1 till at least 3 months after CAR-T cell infusion

Collaborators and Investigators

• Sponsor: Shanghai Changzheng Hospital
• Collaborators: Bioray Laboratories

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2024
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: January 19, 2024
• First Submitted That Met QC Criteria: January 19, 2024
• First Posted (Actual): January 29, 2024

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Metastasis; Castration-resistant Prostate Cancer; Chimeric Antigen Receptor T cell; Prostate-Specific Membrane Antigen; Refractory Castration-resistant Prostate Cancer
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis
• Other Study ID Numbers: 2022-BRL-501

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No