GD2/CD70 Bi-specific CAR-T Cell Therapy

• ClinicalTrials.gov Identifier: NCT05438368
• Recruitment Status: Recruiting
• First Posted: June 30, 2022
• Last Update Posted: June 30, 2022
• Sponsor: Shenzhen Geno-Immune Medical Institute
• Information provided by (Responsible Party): Shenzhen Geno-Immune Medical Institute

Study Description

Brief Summary:

The purpose of this study is to assess the feasibility, safety and efficacy of GD2/CD70 bi-specific CAR-T cell therapy in patients with GD2 and/or CD70 positive tumor. Another goal of the study is to learn more about the function of the GD2/CD70 bi-specific CAR-T cells and their persistency in patients.

Condition or disease	Intervention/treatment	Phase
Cancer Disease	Biological: bi-4SCAR GD2/CD70 T cells	Phase 1; Phase 2

Detailed Description:

Patients with refractory and/or recurrent cancer may 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-GD2/CD70 bi-specific chimeric antigen receptor (bi-4SCAR-GD2/CD70). The chimeric antigen receptor (CAR) molecules enable the T cells to recognize and kill target cells through the recognition of a surface antigen, GD2 or CD70, which is expressed at high levels on cancer 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.

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, hepatoma as well as melanoma. In addition, it has been reported that anti-CD70 CAR T-cells eliminated 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 exhibited a higher affinity and antitumor effect against CD70+ tumor cells. A potential strategy to prevent relapse due to antigen escape is to infuse T-cells capable of recognizing multiple antigens.

To overcome escape of single target antigen in tumor cells and to enhance in vivo CAR-T efficacy, a novel bi-specific GD2/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 GD2 and/or CD70 positive cancer patients.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: GD2/CD70 Bi-specific CAR-T Cells for Cancer Treatment
• Estimated Study Start Date: June 30, 2022
• Estimated Primary Completion Date: December 31, 2025
• Estimated Study Completion Date: June 30, 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: bi-4SCAR-GD2/CD70 T Cell Therapy for GD2 and/or CD70 positive tumor	Biological: bi-4SCAR GD2/CD70 T cells; Infusion of bi-4SCAR GD2/CD70 T cells at 10^6 cells/kg body weight via IV

Outcome Measures

Primary Outcome Measures :

1. Number of patients with adverse events. [ Time Frame: 6 months ]
   Determine the toxicity profile the bi-4SCAR GD2/CD70 cells with Common Toxicity Criteria for Adverse Effects version 4.0

Secondary Outcome Measures :

1. 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.
2. 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.
3. The expansion of bi-4SCAR GD2/CD70 T cells [ Time Frame: 1 year ]
   Scale of CAR copies (for efficacy)
4. The persistence of bi-4SCAR GD2/CD70 T cells [ Time Frame: 1 year ]
   Scale of tumor burden (for efficacy)
5. Survival time of the patients [ Time Frame: 3 years ]
   The progression free survival (PFS) time of the patients treated with the bi-4SCAR GD2/CD70 T cells will be evaluated
6. Survival time of the patients [ Time Frame: 3 years ]
   The overall survival (OS) time of the patients treated with the bi-4SCAR GD2/CD70 T cells will be evaluated

Eligibility Criteria

• Ages Eligible for Study: 1 Year to 75 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Patients with tumors received standard first-line therapy and judged to be non-resectable, metastatic, progressive or recurrent.
2. The expression status of GD2 or CD70 antigens in the tumor tissue will be determined for eligibility. Positive expression is defined by GD2 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 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 CD70-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.

Contacts and Locations

Contacts

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

Locations

China, Guangdong

Shenzhen Geno-immune Medical Institute; Recruiting

Shenzhen, Guangdong, China, 518000

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

Sponsors and Collaborators

Shenzhen Geno-Immune Medical Institute

More Information

• Responsible Party: Shenzhen Geno-Immune Medical Institute
• ClinicalTrials.gov Identifier: NCT05438368
• Other Study ID Numbers: GIMI-IRB-22005
• First Posted: June 30, 2022
• Last Update Posted: June 30, 2022
• Last Verified: June 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Shenzhen Geno-Immune Medical Institute:

CAR-T; cancer; GD2; CD70