PD1 Integrated Anti-PSMA CART in Treating Patients With Castrate-Resistant Prostate Cancer

Study Overview
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Brief Summary
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PD1-PSMA-CART in Treating Patients With Castrate-Resistant Prostate Cancer

Detailed Description
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Clinical trial for the safety and efficacy of Non-viral programmed cell death protein-1(PD1) integrated anti-prostate-specific-membrane-antigen(PSMA) chimeric antigen receptor T(CART) cells in the treatment of Refractory Castrate-Resistant Prostate Cancer(CRPC)

Official Title
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Clinical Trial for the Safety and Efficacy of Non-viral PD1 Integrated Anti-PSMA Chimeric Antigen Receptor T Cells in the Treatment of Refractory Castrate-Resistant Prostate Cancer

Conditions
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Castrate-Resistant Prostate Cancer

Intervention / Treatment
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* Drug: PD1-PSMA-CART cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fully understand and voluntarily sign informed consent. Aged 18 to 75 years old. Expected survival > 6 months. CRPC patients:Serum testosterone reached castration level (<50ng/dl or<1.7nmol/L) and: prostate specific antigen (PSA) increased more than 50% at intervals of one week or three consecutive times, with PSA>2 ng/ml; or imaging scans revealed two or more new lesions or enlargement of soft tissue lesions that met the criteria for evaluating solid tumor response. CRPC patients received abiraterone or chemotherapy for 3 months or more, and were ineffective or progressive (PSA continued to rise for 3 months, or bone scan/whole-body imaging showed local recurrence or new metastasis). Immunohistochemical staining of repetitive biopsy tissues showed the expression of PSMA in tumor cells was more than 50%. Eastern Cooperative Oncology Group (ECOG) score ≤2. Virological examination was negative. Hematological indexes: hemoglobin > 100 g/L, platelet count > 100×10^9/L, absolute neutrophil count > 1.5×10^9/L. Exclusion Criteria: Prior treatment with any CART therapy targeting any target. Prior treatment with any PSMA targeting therapy. Need steroid therapy, except physiological replacement therapy. Prior treatment with any immunotherapy, including tumor vaccine therapy, radium-223, checkpoint inhibitors and others. Subjects with severe mental disorders. Subjects with other malignant tumors. Subjects with severe cardiovascular diseases: a, New York Heart Association (NYHA) stage III or IV congestive heart failure; b, history of myocardial infarction or coronary artery bypass grafting (CABG) within 6 months; c, clinical significance of ventricular arrhythmia, or history of unexplained syncope, non-vasovagal or dehydration; d, history of severe non-ischemic cardiomyopathy; e, the left ventricular ejection fraction (left ventricular ejection fraction< 55%) was decreased by echocardiography or multiple gated acquisition scan (within 8 weeks before peripheral blood mononuclear cell (PBMC) collection), and abnormal interventricular septal thickness and atrioventricular size associated with myocardial amyloidosis. Patients with ongoing or active infection. Organ function: a, Alanine aminotransferase or Aspartate aminotransferase >2.5*Upper limit of normal (ULN); Creatine kinase>1.5*ULN; Creatine kinase isoenzyme >1.5*ULN; Troponin T >1.5*ULN; b, Total bilirubin >1.5*ULN; c, Partial prothrombin time or activated partial thromboplastin time or international standardized ratio > 1.5*ULN without anticoagulant treatment. History of participation in other clinical studies within 3 months or treatment with any gene therapy product. Intolerant or allergic to cyclophosphamide or fludarabine. Subjects not appropriate to participate in this clinical study judged by investigators.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: Group A: 0.5×10^6 cells / kg; Group B: 1.0×10^6 cells / kg; Group C: 2.0×10^6 cells / kg.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PD1-PSMA-CART<br>Patients undergo leukapheresis by receiving cyclophosphamide and fludarabine on days -6 to -4, and then receive PD1-PSMA-CART intravenous injection (IV) at split doses from day 0 on. | Drug: PD1-PSMA-CART cells<br>* PD1-PSMA-CART cells will be given IV at split doses<br>* Other names: Non-viral PD1 integrated anti-PSMA chimeric antigen receptor T cell;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of toxicity graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events | All adverse events (AEs) will be listed and summarized. Summaries of laboratory data will include, at a minimum, treatment-emergent laboratory abnormalities. Summaries of AEs and laboratory abnormalities will be based on the All Treated analysis set. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prostate specific antigen (PSA) response rate | proportion of patients with ≥50% PSA decline from baseline at any time point after therapy and maintained for ≥4weeks | 180 days | 
| Radiographic response rate by RECIST 1.1 & PCWG3 | Proportion of patients with a best response of either complete response or partial response, assessed using Prostate Cancer Working group3(PCWG3) response criteria & Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 | 180 days | 
| Number of persistent CART cells detected by Quantitative Real-time Polymerase Chain Reaction or flow cytometry | Number of persistent CART cells detected by Quantitative Real-time Polymerase Chain Reaction or flow cytometry | 180 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Castrate-Resistant Prostate Cancer