Allogeneic B7H3 CAR-γδT Cell Therapy for Advanced Solid Tumors

NCT ID: NCT06825455

Last Updated: 2025-02-13

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-03-01
• Study Completion Date: 2027-12-31

Brief Summary

γδT cells can directly recognize non-peptide tumor antigens, such as IPP phosphorylated metabolites, without relying on specific major histocompatibility complexes (MHCs). This unique characteristic leads to a lower risk of graft-versus-host disease (GVHD). The clinical safety of γδT cells in allogeneic tumor therapies has been validated multiple times, highlighting their significant potential in developing universal CAR-T cell therapies.

B7H3 (CD276), a member of the B7 negative co-stimulatory molecule family, is minimally expressed or absent in normal tissues but highly expressed in various tumor tissues. As a result, B7H3 is regarded as a highly promising tumor-associated antigen and a universal drug target with substantial therapeutic potential.

By utilizing γδT cells as carrier cells, the development of universal B7H3 CAR-γδT cell injections for advanced solid tumors can effectively address risks such as autologous cell preparation failure and treatment delays. This innovative approach offers a highly efficient solution for solid tumor treatment and holds great promise for advancing immunotherapy in this field

Detailed Description

This study is an open-label, dose-escalation exploratory clinical trial using γδ T cells derived from healthy donors, genetically engineered to express a chimeric antigen receptor (CAR) targeting B7H3 on their membrane. Preclinical in vitro and in vivo experiments demonstrated the modified CAR-γδ T cells possess specific cytotoxicity against B7H3-positive tumor cells.

According to the patients' disease conditions, they were divided into an intravenous infusion group and an intraperitoneal infusion group. Both groups underwent a dose-escalation study using the "3+3" design.

Conditions

Advanced Solid Tumors; Ovarian Cancers; Peritoneal (metastatic) Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intravenous infusion groups

Patients with advanced solid tumor. A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, allogenic targeting B7H3 chimeric antigen receptor γδT cells.

Group Type: EXPERIMENTAL

Fludarabine

Intervention Type: DRUG

Intravenous infusion group:30mg/m2 x 3 days (Day-4\~-2)

Cyclophosphamide

Intervention Type: DRUG

Intravenous infusion group:500mg/m2 x 3 days (Day-4\~-2)

B7H3 CAR-γδT cells

Intervention Type: BIOLOGICAL

A single infusion of 6.0×107 CAR+ cells, 2.0×108CAR+ cells, and 6.0×108CAR+ cells

Abdominal infusion group

Patients with ovarian cancer or peritoneal (metastatic) cancer.Before cell injection, for subjects with obvious ascites, the ascites should be pumped as clean as possible through peritoneal puncture, and then the abdomen should be rinsed with saline before the cell infusion is performed.

Group Type: EXPERIMENTAL

B7H3 CAR-γδT cells

Intervention Type: BIOLOGICAL

A single infusion of 6.0×107 CAR+ cells, 2.0×108CAR+ cells, and 6.0×108CAR+ cells

Interventions

Fludarabine

Intravenous infusion group:30mg/m2 x 3 days (Day-4\~-2)

Intervention Type: DRUG

Cyclophosphamide

Intravenous infusion group:500mg/m2 x 3 days (Day-4\~-2)

Intervention Type: DRUG

B7H3 CAR-γδT cells

A single infusion of 6.0×107 CAR+ cells, 2.0×108CAR+ cells, and 6.0×108CAR+ cells

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Age ≥18 years old, gender is not limited;

2. Expected survival time ≥3 months;

3. ECOG score 0~1;

4. Patients who meet the clinical diagnostic criteria and have a clear pathological diagnosis of malignant solid tumors that have failed standard treatment;

5. Tumor tissue samples (specimens within one year are recommended) positive for B7H3 by immunohistochemical (IHC) staining or flow assay;

6. Presence of at least one evaluable lesion according to RECIST V1.1;

7. Tumors limited to peritoneal (metastatic) and ovarian cancer in patients in the laparotomy group;

8. Substantially normal bone marrow reserve function and normal liver and renal function (laboratory tests need to be fulfilled before the first treatment with cell injection):

Blood: white blood cell count (WBC) ≥3E9/L, lymphocyte count (LY) ≥0.8E9/L, hemoglobin (Hb) ≥80g/L, platelet (PLT) ≥75E9/L; Liver: ALT ≤ 3 × ULN; AST ≤ 3 × ULN; total bilirubin ≤ 3.0 × ULN; Kidney: serum creatinine ≤ 1.5 × upper limit of normal range (ULN); Heart: left ventricular ejection fraction ≥50% on echocardiography; lung: normal oxygen saturation without oxygen.

9. Pregnancy test should be negative for women of childbearing potential and both men and women agree to use effective contraception during treatment and for 1 year thereafter;

10. Be able to understand the requirements and matters of the trial and be willing to participate in the clinical study as required;

11. Sign the trial informed consent form.

Exclusion Criteria

1. Known hypersensitivity, allergy, intolerance, or contraindication to cell infusion or any of the drug components that may be used in the study, including fludarabine and cyclophosphamide;

2. Patients who have been continuously using immunosuppressive drugs within 1 month prior to cell infusion;

3. Cerebrovascular accident or seizure within 6 months prior to signing the informed consent form;

4. Symptomatic brain metastases;

5. a known psychiatric or substance abuse disorder that would interfere with cooperation with the trial requirements;

6. Hepatitis B surface antigen (HBsAg) positivity or hepatitis B core antibody (HBcAb) positivity and a peripheral blood test for hepatitis B virus (HBV) DNA titer that is not within the normal reference range; hepatitis C virus (HCV) antibody positivity and peripheral blood hepatitis C virus (HCV) RNA positivity; human immunodeficiency virus (HIV) antibody positivity; syphilis Positive for syphilis;

7. Serious cardiac disease: including, but not limited to, unstable angina pectoris, myocardial infarction (occurring within 6 months prior to screening), congestive heart failure (NYHA classification ≥ III), and severe arrhythmias;

8. Presence of active or uncontrolled infections requiring systemic therapy (except for mild genitourinary and upper respiratory tract infections);

9. has not recovered from acute toxic effects of prior therapy (prior therapy-induced hematologic or organ toxicity ≥ Grade 2, except for abnormalities related to study disease and medical history);

10. have a confirmed diagnosis of an immunodeficiency

11. suffering from an active infection requiring systemic therapy;

12. a female subject of childbearing potential who plans to become pregnant within 2 years of cell infusion; or a male subject whose partner plans to become pregnant within 2 years of cell infusion;

13. Participation in a clinical study of another innovative drug within 1 month prior to screening;

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking University

OTHER

Sponsor Role: lead

Responsible Party

Shen Lin

Vice President of Beijing Cancer Hospital

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Beijing Cancer Hospital

Beijing, , China

Countries

China

Central Contacts

Lin Shen

Role: CONTACT

doctorshenlin@sina.cn

010-88196561

Changsong Qi

Role: CONTACT

xiwangpku@126.com

010-88196561

Facility Contacts

Changsong Qi, Ph.D

Role: primary

xiwangpku@126.com

+86-13811394004

Other Identifiers

QH10407-ST-01（0）

Identifier Type: -

Identifier Source: org_study_id