clinical study of safety and efficacy of enhanced psma car- t in refractory crpc

Conditions: Metastatic Castration-resistant Prostate Cancer; Castration-resistant Prostate Cancer

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.

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.

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: 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.

Keywords: castration-resistant prostate cancer metastasis prostate-speciﬁc membrane antigen chimeric antigen receptor t cell refractory castration-resistant prostate cancer