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

NCT ID: NCT06228404

Last Updated: 2024-04-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-03
• Study Completion Date: 2025-12-31

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.

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.

Conditions

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

Study Design

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

Study Groups

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.

Group Type: EXPERIMENTAL

Enhanced autologous PSMA-CAR T

Intervention Type: 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;

Interventions

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;

Intervention Type: DRUG

Eligibility Criteria

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

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 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

Chief of Urology

Responsibility Role: PRINCIPAL_INVESTIGATOR

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

Weidong Xu

Role: CONTACT

ayxwd@qq.com

139 1687 9385

Facility Contacts

Shancheng Ren, PhD

Role: primary

renshancheng@gmail.com

13917793885

Other Identifiers

2022-BRL-501

Identifier Type: -

Identifier Source: org_study_id