A Phase I Study of the In Vivo CAR-T Platform for Treating Advanced Malignant Tumors Based on Target Screening
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Incidence of Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
This is a single-arm, open-label, single-center, dose-escalation Phase I platform study designed to evaluate the safety, tolerability, preliminary efficacy, pharmacokinetics, and pharmacodynamics of an in vivo CAR-T therapy (V001 Injection, targeting BCMA, GPRC5D, DLL3,FcRH5, etc.) in patients with advanced malignant tumors.
详细描述
This is a single-arm, open-label, single-center, dose-escalation Phase I platform study designed to evaluate the safety, tolerability, preliminary efficacy, pharmacokinetics, and pharmacodynamics of an in vivo CAR-T therapy (V001 Injection, targeting BCMA, GPRC5D, DLL3, etc.) based on a lentiviral vector platform in patients with advanced malignant tumors (including hematological malignancies and solid tumors). The study employs a platform design, enrolling patients into different cohorts based on target and indication.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years.
- •Histologically confirmed advanced hematological malignancies (e.g., multiple myeloma, lymphoma) or solid tumors (e.g., small cell lung cancer) that are relapsed or refractory.
- •Tumor cells express the relevant target (e.g., BCMA, GPRC5D, DLL3) as required for the specific cohort.
- •ECOG performance status 0-2 (hematological malignancies) or 0-1 (solid tumors) and life expectancy ≥ 3 months.
- •Adequate organ function (e.g., creatinine clearance ≥45 mL/min, LVEF ≥45%).
- •Patients of childbearing potential must agree to use effective contraception during the study and for 1 year after dosing.
- •Signed informed consent form.
排除标准
- •Active, uncontrolled infection.
- •Active central nervous system metastases or involvement.
- •Prior anticancer therapy, radiotherapy, or investigational therapy within specified timeframes before the first study dose.
- •Severe cardiac or pulmonary disease (e.g., NYHA Class III/IV heart failure), severe hepatic or renal impairment.
- •Active Hepatitis B, Hepatitis C, HIV, or syphilis infection.
- •Prior allogeneic hematopoietic stem cell transplantation (within specified window) or active graft-versus-host disease.
- •Pregnancy or lactation.
- •History of severe allergy to any components of the investigational product.
- •Any other condition deemed by the investigator to increase risk or interfere with study results.
研究组 & 干预措施
V001-BCMA
Intravenous administration of V001-BCMA as a single agent for patients with B-cell-related hematologic malignancies. Dose cohorts: 1x10^8 TU、2x10^8 TU、≤4x10^8 TU and ≤8x10^8 TU.
干预措施: V001-BCMA (Genetic)
V001-GPRC5D
Intravenous administration of V001-GPRC5D as a single agent for patients with B-cell-related hematologic malignancies. Dose cohorts: 1x10^8 TU、2x10^8 TU、≤4x10^8 TU and ≤8x10^8 TU.
干预措施: V001-GPRC5D (Genetic)
V001-DLL3
Intravenous administration of V001-BCMA as a single agent for patients with small cell lung cancer. Dose cohorts: 1x10^8 TU、2x10^8 TU、≤4x10^8 TU and ≤8x10^8 TU.
干预措施: V001-DLL3 (Genetic)
V001-FcRH5
Intravenous administration of V001-FcRH5 as a single agent for patients with B-cell-related hematologic malignancies. Dose cohorts: 1x10^8 TU、2x10^8 TU、≤4x10^8 TU and ≤8x10^8 TU.
干预措施: V001-FcRH5 (Genetic)
结局指标
主要结局
Incidence of Dose-Limiting Toxicities (DLTs)
时间窗: Within 28 days after the first infusion
Incidence and characteristics of DLTs graded according to NCI CTCAE v5.0. The DLT observation period is 28 days post-infusion.
Maximum Tolerated Dose (MTD)
时间窗: During the dose-escalation phase (approximately 12 months)
To determine the MTD of V001 Injection.
Incidence of Adverse Events (AEs)
时间窗: From signing ICF until 24 months after the last infusion.
Incidence and severity of treatment-emergent adverse events (TEAEs) graded according to NCI CTCAE v5.0.
次要结局
- Objective Response Rate (ORR)(At Day 28, Months 2, 3, 6, 9, 12, 18, 24 post-infusion)
- Duration of Response (DOR)(From date of the first response until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months)
- Progression-Free Survival (PFS)(From date of infusion until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months)
- Overall Survival (OS)(From the date of infusion until the date of death from any cause, assessed up to 24 months)
- Peak concentration of CAR-T cells in peripheral blood(At multiple timepoints post-infusion up to Month 24)
- time to peak of CAR-T cells in peripheral blood(At multiple timepoints post-infusion up to Month 24)
- AUC of CAR-T cells in peripheral blood(At multiple timepoints post-infusion up to Month 24)