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

Metastatic Castration-resistant Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06228404
• Other study ID #: 2022-BRL-501
• Status: Recruiting
• Phase: Early Phase 1
• Start date: March 3, 2024
• Est. completion date: December 2025

Study information

• Verified date: April 2024
• Source: Shanghai Changzheng Hospital
• Contact: Shancheng Ren, MD/PhD
• Phone: 139 1779 3885
• Email: renshancheng[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: December 2025
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Castration-resistant Prostate Cancer
• Metastatic Castration-resistant Prostate Cancer
• Prostatic Neoplasms

Intervention

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;

Locations

Country	Name	City	State
China	Changzheng hospital	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Shanghai Changzheng Hospital	Bioray Laboratories

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DLT	The number and severity of dose-limiting toxicity (DLT) events	Within 28 Days After Enhanced autologous PSMA-CAR T Infusion
Secondary	PSA response rate	PSA50 response, PSA90 response: PSA response determined as = 50% or = 90% reduction in PSA level from baseline to post-baseline and reassessed at least 3 weeks later	From 3 weeks to 6 months after Enhanced autologous PSMA-CAR T infusion
Secondary	ORR	Objective response rate ORR = CR + PR	6 months after Enhanced autologous PSMA-CAR T infusion