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

Zhejiang University

Status and phase: Completed; Phase 1

Conditions: Castrate-Resistant Prostate Cancer

Treatments: Drug: PD1-PSMA-CART cells

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04768608

2020-CAR-00CH2

Details and patient eligibility

About

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

Full description

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)

Enrollment: 3 patients

Sex: Male

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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3 participants in 1 patient group

PD1-PSMA-CART

Experimental group

Description:

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.

Treatment:

Drug: PD1-PSMA-CART cells