GD2/CD70 Bi-specific CAR-T Cell Therapy

NCT ID: NCT05438368

Last Updated: 2022-06-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-06-30

Study Completion Date

2026-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Cancer Disease

Keywords

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CAR-T cancer GD2 CD70

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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bi-4SCAR-GD2/CD70 T Cell Therapy for GD2 and/or CD70 positive tumor

Group Type EXPERIMENTAL

bi-4SCAR GD2/CD70 T cells

Intervention Type BIOLOGICAL

Infusion of bi-4SCAR GD2/CD70 T cells at 10\^6 cells/kg body weight via IV

Interventions

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bi-4SCAR GD2/CD70 T cells

Infusion of bi-4SCAR GD2/CD70 T cells at 10\^6 cells/kg body weight via IV

Intervention Type BIOLOGICAL

Eligibility Criteria

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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.
Minimum Eligible Age

1 Year

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Shenzhen Geno-Immune Medical Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Shenzhen Geno-immune Medical Institute

Shenzhen, Guangdong, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Lung-Ji Chang, PhD

Role: CONTACT

Phone: 86-0755-86725195

Email: [email protected]

Facility Contacts

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Lung-Ji Chang, PhD

Role: primary

Other Identifiers

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GIMI-IRB-22005

Identifier Type: -

Identifier Source: org_study_id