Biliary Tract Neoplasms, Cholangiocarcinoma, Extrahepatic, Cholangiocarcinoma, Intrahepatic, Cholangiocarcinoma, Perihilar, Gallbladder Cancer
Conditions
Keywords
Adoptive T-cell therapy, Antigen-specific T cells, CD160, Autologous T cell therapy, Biliary tract cancer, Cholangiocarcinoma, APTC - antigen-presenting tumor cell, Lymphodepletion, Phase 1, Investigator-initiated trial
Brief summary
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.
Interventions
BIOLOGICALBTC-Ag-T (ACH-AgT001)
CD160-enhanced autologous antigen-specific T cells. IV infusion.
Combination of cyclophosphamide and Fludarabine as part of lymphodepletion
Sponsors
Shanghai Zhongshan Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open-label, single-arm, sequential dose-escalation design with two operationally distinct modules. Module A uses a 3+3 design across three dose levels to identify dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and the recommended phase 2 dose (RP2D). Module B evaluates the safety and feasibility of repeat lymphodepletion / re-induction at the selected dose. All participants receive the same class of investigational product.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Major Inclusion Criteria: Subjects must meet all of the following criteria to be enrolled: 1\. Age \- Age ≥ 18 years at the time of signing informed consent. 2. Diagnosis * 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 4. 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 6. Adequate venous access and overall condition to tolerate leukapheresis. 7. Washout and lymphocyte recovery before leukapheresis 8. ECOG performance status 0 or 1 9. 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. 11. 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.
Exclusion criteria
Subjects who meet any of the following criteria will be excluded: 1. Mixed/combined hepatocellular-cholangiocarcinoma, ampullary carcinoma, and other histologies not consistent with BTC 2. Prior allogeneic transplant or recent gene-modified cell therapy 3. Active CNS metastases 4. 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). 5. Active autoimmune disease requiring systemic immunosuppression 6. Significant cardiovascular disease 7. Significant pulmonary disease 8. Severe hepatic decompensation 9. Active variceal bleeding, or recent life-threatening portal-hypertension complications that cannot be stably controlled. 10. 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). 11. Severe hypersensitivity. 12. Pregnant or lactating women 13. Concurrent participation in another interventional study 14. Any other condition that, in the investigator's judgment, renders the patient unsuitable for enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DLT incidence and MTD (Module A) | 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) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 24 months | The proportion of patients achieving Complete Response (CR) plus Partial Response (PR), as defined per RECIST v1.1 criteria. |
| Duration of Response (DoR) | 24 months | Duration of response per RECIST v1.1 in responders. |
| Disease Control Rate (DCR) | 24 months | Disease control rate (CR + PR + SD ≥ 12 weeks) per RECIST v1.1. |
| Progression-Free Survival (PFS) | 24 months | Time from the date of Ag-T cell infusion to the first objective documentation of disease progression (per RECIST v1.1) or death due to any cause. |
| Overall Survival (OS) | 36 months | Time from the date of Ag-T cell infusion to death from any cause. |
| Safety & Tolerability | Through 30 days post final infusion; long-term follow-up up to 15 years | Adverse events graded per NCI-CTCAE v6.0; CRS / ICANS per ASTCT criteria; long-term gene-therapy follow-up per regulatory guidance. |
Countries
China
Contacts
CONTACTGuoming Shi, MD, PhD
PRINCIPAL_INVESTIGATORGuoming Shi, MD, PhD
Department of Liver Surgery and Transplantation, Shanghai Zhongshan Hospital, Fudan University
Outcome results
None listed