GD2/CD56 Bi-specific CAR-T Cell Therapy

• ClinicalTrials.gov Identifier: NCT05437328
• 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 GD2/CD56 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)

• Anti-tumor effects [ Time Frame: 1 year ]
  Objective complete response (CR) are assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
• Anti-tumor effects [ 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 GD2/CD56 T cells [ Time Frame: 1 year ]
  Scale of CAR copies
• The persistence of bi-4SCAR GD2/CD56 T cells [ Time Frame: 1 year ]
  Scale of tumor burden (for efficacy)
• Survival time of the patients [ Time Frame: 3 years ]
  The progression free survival (PFS) time of the patients treated with the bi-4SCAR GD2/CD56 T cells will be evaluated
• Survival time of the patients [ Time Frame: 3 years ]
  The overall survival (OS) time of the patients treated with the bi-4SCAR GD2/CD56 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: GD2/CD56 Bi-specific CAR-T Cell Therapy
• Official Title: GD2/CD56 Bi-specific CAR-T Cells for Cancer Treatment
• Brief Summary: The purpose of this clinical trial is to assess the feasibility, safety and efficacy of anti-GD2/CD56 bi-specific CAR-T cell therapy in patients with GD2 and/or CD56 positive cancer. Another goal of the study is to learn more about the function of the anti-GD2/CD56 bi-specific CAR-T cells and their persistency in patients.

Detailed Description

Patients with refractory and/or recurrent malignancies 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 GD2/CD56 bi-specific chimeric antigen receptor (bi-4SCAR-GD2/CD56). The chimeric antigen receptor (CAR) molecules enable the T cells to recognize and kill tumor cells through the recognition of a surface antigen, GD2 or CD56, which is expressed at high levels on tumor cells but not at significant levels on normal tissues.

Disialoganglioside (GD2) is a well-studied tumor associated antigen which is expressed uniformly in nervous system-related tumors but at low levels in normal tissues. Over the past few years, CAR-T therapy against GD2 in tumor has achieved encouraging but modest outcomes. Only a fraction of patients achieved measurable responses. In solid tumors, GD2 CAR-T therapy alone may not be as effective as CAR-T cell therapy in hematological malignancies.

Similar to GD2, the CD56 antigen (NCAM-1) is highly expressed on malignancies with neuronal or neuroendocrine differentiation, including small-cell lung cancer, glioblastoma and neuroblastoma, tumor types for which new therapeutic options are needed. CD56-CAR-T cell therapy has potential for treating patients with aggressive malignancies that are nonresponsive to conventional radiotherapy and chemotherapy, or are unsuitable for hematopoietic stem cell transplantation.

To overcome tumor escape of single target antigen and enhance in vivo CAR-T efficacy, a novel bi-specific GD2/CD56 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 GD2 and/or CD56 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: Malignant Disease

Intervention

Biological: bi-4SCAR GD2/CD56 T cells

Infusion of bi-4SCAR GD2/CD56 T cells at 10^6 cells/kg body weight via IV

Study Arms

Experimental: bi-4SCAR-GD2/CD56 T Cell Therapy for GD2 and/or CD56 positive tumor

Intervention: Biological: bi-4SCAR GD2/CD56 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 tumors received standard first-line therapy and have been judged to be non-resectable, metastatic, progressive or recurrent.
2. The expression status of GD2 or CD56 antigens in the tumor tissue will be determined for eligibility. Positive expression is defined by GD2 and CD56 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 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 GD2 or CD56-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: NCT05437328
• Other Study ID Numbers: GIMI-IRB-22006
• 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