Safety and Efficacy of CD160-Enhanced Autologous Antigen-Specific T-Cells (BTC-Ag-T) in Advanced Biliary Tract Cancer

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

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.

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.