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

NCT06228404 | Active Not Recruiting Early Phase 1

• 1 other identifier: 2022-BRL-501
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Keywords

Castration-resistant Prostate Cancer; Metastasis; Prostate-Specific Membrane Antigen; Chimeric Antigen Receptor T cell; Refractory Castration-resistant Prostate Cancer

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (5)

• Efficacy assessment: PSA changes

  6 months after CAR-T cell infusion

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

  3 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

• Pharmacodynamics (PD) assessment eg. (Level of IL-6)

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

Study Arms (1)

Enhanced autologous PSMA-CAR T:

EXPERIMENTAL

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

Interventions

Enhanced autologous PSMA-CAR T DRUG

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;

Enhanced autologous PSMA-CAR T:

Eligibility Criteria

• Age: 18 Years - 75 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 18-75 years;
• expected survival of more than 6 months;
• metastatic castration-resistant prostate adenocarcinoma (CRPC) patients.
• 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);
• PSMA expression in tumor cells was positive in immunohistochemical staining of prostate/metastatic biopsy tissue before 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 × 109/L; c. neutrophils \> 1.5 × 109/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 \> 2.5ULN; 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;
• participation in other clinical studies in the past three months or previous treatment with any gene therapy product;
• intolerance or hypersensitivity to cyclophosphamide and 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

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

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

Model Details: A：0.25×106/kgBW B: 0.75×106/kgBW C: 2×106/kgBW

Study Record Dates

• First Submitted: January 19, 2024
• First Posted: January 29, 2024
• Study Start: March 3, 2024
• Primary Completion: May 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)