A Phase I, Open-label Study to Evaluate the Safety and Efficacy of CD160-enhanced Autologous BTC-Ag-T Cells in Advanced Biliary Tract Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- DLT incidence and MTD (Module A)
研究概览
简要总结
BTC-Ag-T (ACH-AgT001) is an autologous experimental T-cell therapy designed for advanced biliary tract cancer. This is an open-label, single-arm Phase 1 study to evaluate the safety, tolerability, and preliminary efficacy of BTC-Ag-T in patients with advanced, unresectable, or metastatic biliary tract cancer who have failed standard-of-care therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Major Inclusion Criteria:
- •Subjects must meet all of the following criteria to be enrolled:
- •- Age ≥ 18 years at the time of signing informed consent.
- •Histologically or cytologically confirmed biliary tract malignancy (intrahepatic, perihilar, or distal extrahepatic cholangiocarcinoma, or gallbladder cancer).
- •3. Disease status
- •Locally advanced unresectable or metastatic disease
- •Prior systemic therapy
- •Patients (including those with refractory BTC and those with postoperative recurrence) must have received prior gemcitabine-based chemotherapy in combination with a PD-1/PD-L1 inhibitor.
- •5. Measurable disease
- •At least one measurable lesion per RECIST v1.1 at baseline imaging.
- •Sufficient viable tumor tissue from biopsy for antigen-presenting tumor cell (APTC) manufacturing
- •Adequate venous access and overall condition to tolerate leukapheresis.
- •Washout and lymphocyte recovery before leukapheresis
- •ECOG performance status 0 or 1
- •Organ function
- •Hematology (no growth-factor support or transfusion within 5 days of testing, unless otherwise stated): ANC ≥ 1.0 × 10⁹/L; platelets ≥ 75 × 10⁹/L; hemoglobin ≥ 8.0 g/dL (transfusion to reach this threshold is permitted).
- •Hepatic: total bilirubin ≤ 2.0 × ULN (≤ 3.0 × ULN allowed for documented Gilbert syndrome); AST and ALT ≤ 5.0 × ULN.
- •Renal: serum creatinine ≤ 1.5 × ULN, or estimated creatinine clearance (e.g., Cockcroft-Gault) ≥ 40 mL/min.
- •Adequate cardiopulmonary reserve to tolerate lymphodepleting conditioning and cell infusion in the investigator's judgment.
- •10. Viral serology
- •No evidence of uncontrolled active viral infection.
- •HIV-1/2 negative.
- •Hepatitis B: HBV DNA is negative.
- •Hepatitis C: HCV RNA is negative.
- •Contraception
- •Women of childbearing potential and men whose partners are of childbearing potential must agree to use highly effective contraception from the time of informed consent through at least 12 months after BTC-Ag-T infusion (or longer if required by local regulation).
- •12. Pregnancy status
- •Women of childbearing potential must have a negative serum or urine pregnancy test at screening.
- •13. Informed consent
- •Able to understand and willing to sign a written informed consent document, and willing to comply with study procedures.
排除标准
- •Subjects who meet any of the following criteria will be excluded:
- •Mixed/combined hepatocellular-cholangiocarcinoma, ampullary carcinoma, and other histologies not consistent with BTC
- •Prior allogeneic transplant or recent gene-modified cell therapy
- •Active CNS metastases
- •Patients with uncontrolled or high-risk active infection are excluded, including hepatitis B virus (HBV), hepatitis C virus (HCV), Epstein-Barr virus (EBV), and active tuberculosis (TB).
- •Active autoimmune disease requiring systemic immunosuppression
- •Significant cardiovascular disease
- •Significant pulmonary disease
- •Severe hepatic decompensation
- •Active variceal bleeding, or recent life-threatening portal-hypertension complications that cannot be stably controlled.
- •Another primary malignancy within the past 3 years, except: tumors treated with curative intent and at low risk of recurrence (e.g., adequately treated basal- or squamous-cell skin cancer, in-situ cervical cancer, or low-Gleason localized prostate cancer, occult thyroid carcinoma).
- •Severe hypersensitivity.
- •Pregnant or lactating women
- •Concurrent participation in another interventional study
- •Any other condition that, in the investigator's judgment, renders the patient unsuitable for enrollment.
研究组 & 干预措施
CD160-Enhanced Autologous BTC-Ag-T
Autologous CD160-enhanced BTC-specific antigen-specific T cells (ACH-AgT001) administered IV after fludarabine/cyclophosphamide lymphodepletion. Module A uses a 3+3 dose escalation. Module B evaluates repeat lymphodepletion / re-induction at the selected dose.
干预措施: BTC-Ag-T (ACH-AgT001) (Biological)
CD160-Enhanced Autologous BTC-Ag-T
Autologous CD160-enhanced BTC-specific antigen-specific T cells (ACH-AgT001) administered IV after fludarabine/cyclophosphamide lymphodepletion. Module A uses a 3+3 dose escalation. Module B evaluates repeat lymphodepletion / re-induction at the selected dose.
干预措施: Cyclophosphamide and Fludarabine (Drug)
结局指标
主要结局
DLT incidence and MTD (Module A)
时间窗: DLT window: Day 0 through Day 28
Proportion of subjects with protocol-defined dose-limiting toxicities (Grade ≥3 cytokine release syndrome (CRS) or Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), persistent Grade 4 cytopenia, or specified Grade ≥3 non-hematologic toxicity attributed to BTC-Ag-T); MTD identified per 3+3 rules.
Safety of repeat lympho-depletion(LD)/re-induction (Module B)
时间窗: Through Day 150; long-term follow-up up to 15 years
Incidence and severity of treatment-emergent adverse events graded per Common Terminology Criteria for Adverse Events (CTCAE) v6.0 and American Society for Transplantation and Cellular Therapy (ASTCT) criteria for CRS / ICANS, summarized by lymphodepletion cycle.
次要结局
- Objective Response Rate (ORR)(24 months)
- Duration of Response (DoR)(24 months)
- Disease Control Rate (DCR)(24 months)
- Progression-Free Survival (PFS)(24 months)
- Overall Survival (OS)(36 months)
- Safety & Tolerability(Through 30 days post final infusion; long-term follow-up up to 15 years)
研究者
Jia Fan
Professor
Shanghai Zhongshan Hospital