PSMA/CD70 Bi-specific CAR-T Cell Therapy

• ClinicalTrials.gov Identifier: NCT05437341
• Recruitment Status: Recruiting
• First Posted: June 29, 2022
• Last Update Posted: June 29, 2022
• Sponsor: Shenzhen Geno-Immune Medical Institute
• Information provided by (Responsible Party): Shenzhen Geno-Immune Medical Institute

Tracking Information

• First Submitted Date: June 21, 2022
• First Posted Date: June 29, 2022
• Last Update Posted Date: June 29, 2022
• Estimated Study Start Date: June 30, 2022
• Estimated Primary Completion Date: December 31, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 25, 2022)

Number of patients with adverse events. [ Time Frame: 6 months ]

Determine the toxicity profile the bi-4SCAR PSMA/CD70 cells with Common Toxicity Criteria for Adverse Effects version 4.0

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: June 25, 2022)

• Tumor remission response evaluation [ Time Frame: 1 year ]
  Objective complete response (CR) are assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
• Tumor remission response evaluation [ Time Frame: 1 year ]
  Objective partial response (PR)) are assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
• The expansion of bi-4SCAR PSMA/CD70 T cells [ Time Frame: 1 year ]
  Scale of CAR copies (for efficacy)
• The persistence of bi-4SCAR PSMA/CD70 T cells [ Time Frame: 1 year ]
  Scale of tumor burden (for efficacy)
• Survival time of the patients [ Time Frame: 3 years ]
  The overall survival (OS) time of the patients treated with the bi-4SCAR PSMA/CD70 T cells will be evaluated
• Survival time of the patients [ Time Frame: 3 years ]
  The progression free survival (PFS) time of the patients treated with the bi-4SCAR PSMA/CD70 T cells will be evaluated

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: PSMA/CD70 Bi-specific CAR-T Cell Therapy
• Official Title: PSMA/CD70 Bi-specific CAR-T Cells for Cancer Treatment
• Brief Summary: The purpose of this study is to assess the feasibility, safety and efficacy of anti-PSMA/CD70 bi-specific CAR-T cell therapy in patients with CD70 and PSMA positive malignancies. Another goal of the study is to learn more about the function of the PSMA/CD70 bi-specific CAR-T cells and their persistency in patients.

Detailed Description

Patients with refractory and/or recurrent cancer have poor prognosis despite complex multimodal therapy; therefore, novel curative approaches are needed. The investigators attempt to use T cells genetically modified to express a 4th generation lentiviral anti-PSMA/CD70 bi-specific chimeric antigen receptor (bi-4SCAR-PSMA/CD70). The chimeric antigen receptor (CAR) molecules enable the T cells to recognize and kill tumor cells through the recognition of a surface antigen, CD70 or PSMA, which is expressed at high levels on tumor cells but not at significant levels on normal tissues.

CD70 is a promising therapeutic target due to its restricted expression in normal tissues and overexpression in malignant tissues. Expression of CD70 was observed on multiple tumor types including kidney, breast, esophageal, liver, colon cancer, glioma, lymphoma as well as melanoma. In addition, it has been reported that anti-CD70 CAR T-cell therapy eliminated primary CD70-positive cells and had strong anti-tumor effects in preclinical animal models. The CD70 targeted CAR-T cells with binding moiety of CD70 specific scFv exhibit a higher affinity and antitumor effect against CD70+ tumor cells.

Prostate-specific membrane antigen (PSMA) is expressed in normal prostate and upregulated in prostate tumor. However, PSMA is not restricted to prostate cancer and it is known that PSMA is enriched in the tumor stromal environment. Based on immunostaining, it is confirmed that PSMA is expressed in a variety of solid tumors, including brain tumor, neuroblastoma and some lymphomas. Therefore, PSMA is a promising target for immunotherapy of many types of cancer.

A potential strategy to prevent relapse due to antigen escape is to infuse T-cells capable of recognizing multiple antigens. To overcome tumor escape of single target antigen and enhance in vivo CAR-T efficacy, a novel bi-specific PSMA/CD70 CAR-T therapy regimen is developed to include booster and consolidation CAR-T applications to target highly-refractory cancer. The aim is to evaluate safety and long term efficacy of the bi-CAR-T therapy strategy in CD70 and/or PSMA positive cancer patients.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Cancer Disease

Intervention

Biological: bi-4SCAR PSMA/CD70 T cells

Infusion of bi-4SCAR PSMA/CD70 T cells at 10^6 cells/kg body weight via IV

Study Arms

Experimental: bi-4SCAR-PSMA/CD70 T Cell Therapy for CD70 and/or PSMA positive cancer

Intervention: Biological: bi-4SCAR PSMA/CD70 T cells

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 25, 2022): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 30, 2026
• Estimated Primary Completion Date: December 31, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Patients with tumor cells have received standard first-line therapy and have been judged to be non-resectable, metastatic, progressive or recurrent.
2. The expression status of CD70 or PSMA antigens in the tumor tissue will be determined for eligibility. Positive expression is defined by CD70 and 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 be 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, selected targeted agent 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 enrollment 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 4 weeks following completion of therapy are eligible.
3. Previous treatment with other genetically engineered CD70 or PSMA-specific CAR T cells.
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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year to 75 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Lung-Ji Chang, PhD; 86-0755-86725195; c@szgimi.org

• Listed Location Countries: China

Administrative Information

• NCT Number: NCT05437341
• Other Study ID Numbers: GIMI-IRB-22004
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Shenzhen Geno-Immune Medical Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Shenzhen Geno-Immune Medical Institute
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Shenzhen Geno-Immune Medical Institute
• Verification Date: June 2022