Allogeneic B7H3 CAR-γδT Cell Therapy for Advanced Solid Tumors

Trial statusNot yet recruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorPeking University

About this trial

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

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age ≥18 years old, gender is not limited;

Expected survival time ≥3 months;

ECOG score 0~1;

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

Disqualifiers

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;

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

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

Symptomatic brain metastases;

Trial design

Design model

Single group

Treatments tested in this trial

  • Fludarabine

    Drug

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

  • Cyclophosphamide

    Drug

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

  • B7H3 CAR-γδT cells

    Biological/Vaccine

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

Treatment groups

18 Participants
are divided into 2 treatment groups
Group A: Intravenous infusion groupsExperimental treatment 3 interventions
Group B: Abdominal infusion groupExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Incidence of Adverse Events (AEs)

AE is defined as any adverse medical event from the date of randomization to 12 months after B7H3 CAR-γδT cells infusion. Among them, cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria, graft-versushost disease (GVHD) according to criteria defined by the Mount Sinai Acute GVHD International Consortium. Other AEs were graded according to common terminology criteria for adverse events (CTCAE) v5.0.

Time frame
12 months

Secondary outcomes

1

Best objective Response Rate

The incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or unevaluable (UE) as the best response to treatment assessed by investigators and based on the RECIST 1.1 criterion.

Time frame
12 months
2

Duration of Response (DOR)

DOR is defined as the date of their first CR or PR (which is subsequently confirmed) to PD assessed by investigators and based on the RECIST 1.1 criterion, or death regardless of cause.

Time frame
12 months
3

Progression Free Survival (PFS)

PFS is defined as the time from the B7H3 CAR-γδT cells infusion date to the date of disease progression assessed by investigators and based on the RECIST 1.1 criterion, or death any cause. Participants not meeting the criteria for progression by the analysis data cutoff date were censored at their last evaluable disease assessment date.

Time frame
12 months
4

Overall Survival (OS)

OS is defined as the time from B7H3 CAR-γδT cells infusion to the date of death. Subjects who have not died by the analysis data cutoff date will be censored at their last contact date.

Time frame
12 months

Other outcomes

Sponsors and contacts

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Peking University

Lead sponsor

Peking University Cancer Hospital & Institute

Sponsor institution

This trial is not recruiting at the moment. You can still explore other options: