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

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

Summary: this is a single-arm, single-center, open-label clinical trial designed to evaluate the clinical safety and tolerability of different doses of prostate-specific membrane antigen (psma)-universal chimeric antigen receptor (ucar) t-lymphocytes (psma-ucar t) for the treatment of patients with refractory castration-resistant prostate cancer (crpc).

this is a single-arm, single-center, open-label clinical trial, which aims to evaluate safety and clinical efficacy of different doses of psma-ucar t (brl-302) in treating patients with refractory crpc. three patients will be firstly enrolled at a dose level (dl) of 5.0 × 10\^6cells/kg in the dl1 group. based on preliminary safety data, efficacy information, and pk/pd parameters obtained at dl1 cohort, the investigator may enroll another three patients in a decreased dose level group of dl-2: 3 × 10\^6 cells/kg or dl-1:1 × 10\^6 cells/ kg, after thorough discussions between the investigators.

Eligibility criteria:
inclusion criteria: 1. fully understood and voluntarily signed informed consent for this study; 2. male, aged 18-80 years; 3. expected survival of more than 6 months; 4. metastatic castration-resistant prostate adenocarcinoma (crpc) patients: have received crpc standard treatment (such as novel hormone therapies, chemotherapy and radium-223, etc., one or more of the combination therapy) after the diagnosis of crpc, and is ineffective or progressive :psa continued rising for 3 months, or bone scan/whole-body mri/pet-ct showed local recurrence or new metastatic lesions, demonstrating disease progression; 5. psma expression in tumor cells was positive in immunohistochemical staining of prostate/metastatic biopsy tissue before enrollment (within 6 months prior to enrollment); 6. ecog score \< 2 ; 7. 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); 8. hematological parameters met the following criteria: a. hemoglobin \> 100 g/l; b. platelet count \> 100 × 10\^9/l; c. neutrophils \> 1.5 × 10\^9/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 \> 2.5\*upper limit of normal (uln); ck \> uln; ck-mb \> uln; tnt \> 1.5\*uln; b. total bilirubin \> 1.5\*uln; c. partial prothrombin time or activated partial thromboplastin time or international normalized ratio \> 1.5\*uln 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 or fludarabine chemotherapy; 11. unsuitability to participate in this clinical study in the opinion of the investigator.

Keywords: prostate cancer universal car-t metastatic castration-resistant prostate cancer chimeric antigen receptor t cell