Clinical trial NCT06228404: Clinical Study of Safety and Efficacy of Enhanced PSMA CAR- T in Refractory CRPC
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Metastatic Castration-resistant Prostate Cancer
Castration-resistant Prostate Cancer
Keywords: Castration-resistant Prostate Cancer
Metastasis
Prostate-Speciﬁc Membrane Antigen
Chimeric Antigen Receptor T cell
Refractory Castration-resistant Prostate Cancer
Lead sponsor: Shanghai Changzheng Hospital
Sponsor class: OTHER
Collaborators: name: Bioray Laboratories
First posted: 2024-01-29
Enrollment: 18
Sex: MALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: A：0.25×106/kgBW B: 0.75×106/kgBW C: 2×106/kgBW
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: DLT
timeFrame: Within 28 Days After Enhanced autologous PSMA-CAR T Infusion
Secondary outcomes:
measure: PSA response rate
timeFrame: From 3 weeks to 6 months after Enhanced autologous PSMA-CAR T infusion
measure: ORR
timeFrame: 6 months after Enhanced autologous PSMA-CAR T infusion
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Changzheng hospital
state: Shanghai
Study officials:
References: