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

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

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

Study Overview

• Status: Completed
• Conditions: Castrate-Resistant Prostate Cancer
• Intervention / Treatment: Drug: PD1-PSMA-CART cells

Detailed 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)

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The First Affiliated Hospital, Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PD1-PSMA-CART; 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; PD1-PSMA-CART cells will be given IV at split doses; Other Names: Non-viral PD1 integrated anti-PSMA chimeric antigen receptor T cell

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Zhejiang University
• Collaborators: Bioray Laboratories
• Investigators: Principal Investigator: Weijia Fang, MD, The First Affiliated Hospital, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): December 23, 2021
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): May 30, 2023

Study Registration Dates

• First Submitted: February 18, 2021
• First Submitted That Met QC Criteria: February 23, 2021
• First Posted (Actual): February 24, 2021

Study Record Updates

• Last Update Posted (Actual): July 17, 2023
• Last Update Submitted That Met QC Criteria: July 14, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Castrate-Resistant Prostate Cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 2020-CAR-00CH2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No