Clinical trial NCT06825455: Allogeneic B7H3 CAR-γδT Cell Therapy for Advanced Solid Tumors
Official title: Clinical Study of the Safety and Tolerability of B7H3 CAR-γδT Cell Injection in the Treatment of Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: Advanced Solid Tumors
Ovarian Cancers
Peritoneal (metastatic) Cancer
Keywords: cell therapy
γδT
CAR-T
Lead sponsor: Peking University
Sponsor class: OTHER
First posted: 2025-02-13
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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;

Primary outcomes:
measure: Incidence of Adverse Events (AEs)
timeFrame: 12 months
Secondary outcomes:
measure: Best objective Response Rate
timeFrame: 12 months
measure: Duration of Response (DOR)
timeFrame: 12 months
measure: Progression Free Survival (PFS)
timeFrame: 12 months
measure: Overall Survival (OS)
timeFrame: 12 months
measure: Immunogenicity: Proportion of subjects with anti drug antibody (ADA)
timeFrame: 12 months
measure: Pharmacodynamics
timeFrame: Up to 28 days after infusion
measure: Pharmacokinetics
timeFrame: 12 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
Study officials:
References: