Clinical Study of the Safety and Efficacy of Allogeneic TCR-enhanced Vδ2 T Cell in Patients With Malignant Tumors.

Официальное название

A Clinical Study on the Safety and Efficacy of Allogeneic TCR-enhanced Vδ2 T Cell Injection in the Treatment of Patients With Malignant Tumors

Обзор

The allogeneic TCR-enhanced Vδ2 T cell product is a novel genetically engineered cellular therapeutic. By engineering a specific BTN protein-binding moiety on its cell surface, this product harnesses the intrinsic tumoricidal potential of endogenous Vδ2 T cells and augments BTN protein recognition capability, thereby significantly boosting tumor cell killing potency. Notably, this engineered cell product exhibits no expression of co-stimulatory signaling domains and CD3ζ domains. This design circumvents T cell exhaustion triggered by overactivation and markedly enhances the in vivo persistence of therapeutic cells. This is an open, prospective, open-label Phase I/II clinical trial designed to assess the safety and therapeutic efficacy of allogeneic TCR-enhanced Vδ2 T cell injection in patients with relapsed or refractory hematologic malignancies and advanced solid tumors.

Вмешательства

• Биопрепарат Allogeneic TCR-enhanced Vδ2 T cell Injection
  Allogeneic TCR-enhanced Vδ2 T cells in a standard 3+3 dose-escalation design. Three predefined dose levels are investigated: Dose 1: 1×10\^7 enTCR Vδ2T cells/kg, Dose 2: 3×10\^7 enTCR Vδ2T cells/kg, and Dose 3: 6×10\^7 enTCR Vδ2T cells/kg.
• Препарат Cyclophosphamide injection
  For patients with hematological tumors, cyclophosphamide should be administered from day 5 to day 3 before cell infusion, with a recommended dose of 500 - 1000 mg/m² per day. For patients with solid tumors, cyclophosphamide should be administered from day 4 to day 3 before cell infusion, with a recommended dose of 500 - 700 mg/m² per day.
• Препарат Fludarabine Injection
  For patients with hematological tumors, fludarabine should be administered from day 5 to day 3 before cell infusion, and the recommended dose is 30 - 50 mg/m² per day. For patients with solid tumors, fludarabine should be administered from day 4 to day 3 before cell infusion, with a recommended dose of 30 - 40 mg/m² per day.
• Препарат Albumin paclitaxel injection
  This is only applicable to patients with solid tumors. It should be administered on the fifth day before cell infusion. The recommended dosage is 150-200 mg/m² per day.

Первичные конечные точки

• Adverse Event [Срок оценки: 12 months]
• DLTs [Срок оценки: 28 days after cell infusion]

Вторичные конечные точки (5)

• PK(Pharmacokinetics):Number and Copy Number of allogeneic TCR-enhanced Vδ2 T cell [Срок оценки: 12 months]
• PD(Pharmacodynamics):changes over time [Срок оценки: 12 months]
• Objective Response Rate [Срок оценки: 12 months after cell infusion]
• Overall Survival(OS) [Срок оценки: 12 months]
• Progression Free Survival (PFS) [Срок оценки: 12 months]

Критерии участия

Критерии включения

• Age 18-75 (inclusive).
• Expected survival time ≥ 3 months.
• Meets current clinical diagnostic criteria with a confirmed diagnosis of a malignant hematologic tumor or solid tumor, and has failed standard therapy (for solid tumors, at least one evaluable lesion according to RECIST v1.1 is required).
• Adequate bone marrow reserve and essentially normal liver and kidney function (laboratory tests must meet the following criteria prior to the first allogeneic TCR-enhanced Vδ2 T cell treatment):
• Hematology: White Blood Cell Count (WBC) ≥ 2.5×10⁹/L, Lymphocyte Count (LY) ≥ 0.8×10⁹/L, Hemoglobin (Hb) ≥ 80 g/L, Platelets (PLT) ≥ 75×10⁹/L.
• Liver: ALT ≤ 3 × ULN; AST ≤ 3 × ULN; Total Bilirubin ≤ 3.0 × ULN.
• Kidney: Serum Creatinine ≤ 1.5 × ULN.
• Cardiac: Left Ventricular Ejection Fraction (LVEF) ≥ 50% as measured by echocardiogram.
• Pulmonary: Normal oxygen saturation without supplemental oxygen.
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-1.
• A negative pregnancy test is required for women of childbearing potential. Both male and female subjects must agree to use effective contraception during the treatment period and for 1 year thereafter.
• Able to understand the trial requirements and is willing to participate in the clinical study as required.
• Voluntarily signs the informed consent form for the clinical trial.

Критерии исключения

• Known history of allergy, hypersensitivity, intolerance, or contraindication to allogeneic TCR-enhanced Vδ2 T cell or any components of the study drugs (including fludarabine, cyclophosphamide and albumin paclitaxel).
• Continuous use of immunosuppressants within 1 month prior to allogeneic TCR-enhanced Vδ2 T cell infusion.
• History of cerebrovascular accident or seizure within 6 months prior to signing the informed consent.
• Symptomatic brain metastases.
• Known psychiatric or substance abuse disorders that would compromise compliance with study requirements.
• Positive for Hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb) with detectable Hepatitis B virus (HBV) DNA levels outside the normal reference range; positive for Hepatitis C virus (HCV) antibody with detectable HCV RNA; positive for Human Immunodeficiency Virus (HIV) antibody; positive for syphilis.
• Severe cardiac disease, including but not limited to unstable angina, myocardial infarction (within 6 months prior to screening), congestive heart failure (NYHA Class ≥ III), and severe arrhythmia.
• Active or uncontrolled infection requiring systemic therapy (except for mild urogenital and upper respiratory tract infections).
• Has not recovered from acute toxic effects of prior therapy (i.e., persisting hematological or organ toxicity ≥ Grade 2 related to prior therapy, excluding abnormalities associated with the study disease and its history).
• Diagnosed with immunodeficiency.
• Active infection requiring systemic treatment.
• Female subjects of childbearing potential planning pregnancy within 2 years after cell infusion; or male subjects whose partners are planning pregnancy within 2 years after cell infusion.
• Participation in another investigational drug clinical study within 1 month prior to screening.
• Last anti-tumor therapy administered less than 5 half-lives of the drug prior to planned allogeneic TCR-enhanced Vδ2 T cell infusion.
• Any other condition deemed by the investigator to make the subject unsuitable for participation in this study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Biotherapeutic Department of Chinsese PLA Gereral Hospital — Пекин

Идентификаторы

NCT: NCT07570563 · CHN-PLAGH-BT-100

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗