PSMA-specific CAR-T Cell Therapy

Phase I/II Clinical Trial of 4SCAR-PSMA T Cell Therapy Targeting PSMA Positive Malignancies

The purpose of this clinical trial is to assess the feasibility, safety and efficacy of PSMA-specific CAR-T cell therapy in patients with PSMA positive tumor. Another goal of the study is to learn more about the function of the PSMA CAR-T cells and their persistency in the patients.

Study Overview

• Status: Recruiting
• Conditions: PSMA Positive Tumors or Tumor Tissues
• Intervention / Treatment: Biological: 4SCAR-PSMA T cells

Detailed Description

Prostate-specific membrane antigen (PSMA) is expressed in normal prostate and is upregulated in prostate tumor. Therefore, PSMA is a promising target for antigen-specific immunotherapy in patients with prostate cancer. However, it has been reported that PSMA expression is not restricted to prostate cancer and PSMA is often enriched in the tumor stromal environment. By immunostaining, we found that PSMA is expressed in a variety of solid tumors, including brain tumor, neuroblastoma and some lymphoma tumor tissues.

This study aims to use T cells obtained directly from the patient, which can be genetically modified to express PSMA-specific chimeric antigen receptor (CAR). The CAR molecules enable the T cells to recognize and kill tumor cells or tumor stromal tissues through the recognition of a surface antigen, PSMA. This study will evaluate the side effects and the best dose of anti-PSMA CAR-T cells to target PSMA positive tumors and tumor microenvironment.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • Recruiting
      • Shenzhen Geno-immune Medical Institute
    • Shenzhen, Guangdong, China, 518000
      • Recruiting
      • Shenzhen Children's Hospital
      • Contact: Xiuli Yuan, MD; Phone Number: 86-18938690212; Email: 18938690212@163.com
    • Shenzhen, Guangdong, China, 518101
      • Recruiting
      • Shenzhen Hospital of Southern Medical University
      • Contact: Jie Mao, MD; Phone Number: 86-0755-233; Email: myw921@163.com
    • Shenzhen, Guangdong, China, 518107
      • Recruiting
      • The Seventh Affilliated Hospital of Sun Yat-Sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with tumors have received standard first-line therapy and have been judged to be non-respectable, metastatic, progressive or recurrent.
2. The expression status of PSMA antigens in the tumor tissue will be determined for eligibility. Positive expression is defined by PMSA antibody staining results based on immunohistochemistry or flow cytometry analyses.
3. Body weight greater than or equal to 10 kg.
4. Age: ≥1 year and ≤ 75 years of age at the time of enrollment.
5. Life expectancy: at least 8 weeks.

6. Prior Therapy:

   There is no limit to the number of prior treatment regimens. Any grade 3 or 4 non-hematologic toxicity of any previous therapy must have resolved to grade 2 or less.

7. Participant must not have received hematopoietic growth factors for at least 1 week prior to mononuclear cells collection.
8. At least 7 days must have elapsed since the completion of therapy with a biologic agent, targeted agent, tyrosine kinase inhibitor or a metronomic non-myelosuppressive regimen.
9. At least 4 weeks must have elapsed since prior therapy that included a monoclonal antibody.
10. At least 1 week since any radiation therapy at the time of study entry.
11. Karnofsky/jansky score of 60% or greater.
12. Cardiac function: Left ventricular ejection fraction greater than or equal to 40/55 percent.
13. Pulse Ox greater than or equal to 90% on room air.
14. Liver function: defined as alanine transaminase (ALT) <3x upper limit of normal (ULN), aspartate aminotransferase (AST) <3x ULN; serum bilirubin and alkaline phosphatase <2x ULN.
15. Renal function: Patients must have serum creatinine less than 3 times upper limit of normal.
16. Marrow function: White blood cell count ≥1000/ul, Absolute neutrophil count ≥500/ul, Absolute lymphocyte count ≥500/ul, Platelet count ≥25,000/ul (not achieved by transfusion).
17. Patients with known bone marrow metastatic disease will be eligible for study as long as they meet hematologic function criteria, and the marrow disease does not have hematologic toxicity.
18. For all patients enrolled in this study, themselves or their parents or legal guardians must sign an informed consent and assent.

Exclusion Criteria:

1. Existing severe illness (e.g. significant cardiac, pulmonary, hepatic diseases, etc.) or major organ dysfunction, or greater than grade 2 hematologic toxicity.
2. Untreatable central nervous system (CNS) metastasis: Patients with previous CNS tumor involvement that has been treated and is stable for at least 6 weeks following completion of therapy are eligible.
3. Previous treatment with other genetically engineered PSMA-specific CAR T cells or antibody therapy.
4. Active HIV, Hepatitis B virus (HBV), Hepatitis C virus (HCV) infection or uncontrolled infection.
5. Patients who require systemic corticosteroid or other immunosuppressive therapy.
6. Evidence of tumor potentially causing airway obstruction.
7. Inability to comply with protocol requirements.
8. Insufficient CAR T cells availability.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 4SCAR-PSMA Cell Therapy for PSMA positive tumor; Infusion of 4SCAR-PSMA T cells at 10^6 cells/kg body weight via IV	Biological: 4SCAR-PSMA T cells; Infusion of 4SCAR-PSMA T cells at 10^6 cells/kg body weight via IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with adverse events.	Determine the toxicity profile the 4SCAR-PSMA cells with Common Toxicity Criteria for Adverse Effects version 4.0	3 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-tumor effects	Objective responses (complete response (CR) + partial response (PR)) are assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.	1 year
The expansion and persistence of 4SCAR-PSMA T cells	Scale of CAR copies and tumor burden (for efficacy)	1 year
Survival time of the patients	The survival time of the patients treated with the 4SCAR-PSMA T cells, including progression free survival (PFS) and overall survival (OS) will be evaluated.	3 year

Collaborators and Investigators

• Sponsor: Shenzhen Geno-Immune Medical Institute
• Collaborators: The Seventh Affiliated Hospital of Sun Yat-sen University; Shenzhen Children's Hospital; Shenzhen Hospital of Southern Medical University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Anticipated): October 31, 2023
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: June 9, 2020
• First Submitted That Met QC Criteria: June 10, 2020
• First Posted (Actual): June 12, 2020

Study Record Updates

• Last Update Posted (Actual): June 12, 2020
• Last Update Submitted That Met QC Criteria: June 10, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Prostate cancer; PSMA; CAR; Tumor microenvironment; chimeric antigen receptor; adoptive T cell transfer
• Other Study ID Numbers: GIMI-IRB-20003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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