Clinical Study of VG161 in Advanced Intrahepatic Cholangiocarcinoma

Inclusion Criteria:

1. Subjects must fully understand and give informed consent to this study beforethe trial, and voluntarily sign a written informed consent form.

2. aged 18 to 75 years (inclusive), male or female. 3. patients withhistologically or cytologically confirmed advanced intrahepaticcholangiocarcinoma.

3. According to the Guidelines for the Diagnosis and Treatment of BiliaryMalignant Tumors (CSCO), patients must have previously received at leastsystemic first-line therapy for advanced intrahepatic cholangiocarcinoma andfailed, or cannot tolerate treatment. Patients who received preoperativeneoadjuvant chemotherapy or postoperative adjuvant chemotherapy were counted ashaving failed first-line treatment if disease progression occurred duringchemotherapy or within 6 months after stopping chemotherapy; 5. According toRECIST 1.1 criteria, one or more CT examinations are determined to bemeasurable and meet the requirements for the volume administered for the firstinjection, tumor lesions and/or metastases (the injected lesions shouldpreferably be the main tumor burden lesions) that can be injected underultrasound or CT guidance, and the baseline longest diameter of the injectedlesions (lymph node lesions are short diameters) is > 1.5 cm.

4. Herpes simplex virus type I (HSV-1) antibody test results (HSV-1 IgG or HSV-1IgM) are positive.

5. ECOG performance score 0-1. 8. Expected survival time of more than 3 months. 9.Adequate organ function:

6. Blood routine (no blood transfusion or colony-stimulating factor treatmentwithin 14 days): ANC ≥ 1.5 × 109/L, PLT ≥ 75 × 109/L, Hb ≥ 85 g/L;

7. Liver function: TBIL ≤ 1.5 × ULN, ALT ≤ 3 × ULN, AST ≤ 3 × ULN;

8. Child-Pugh A-B;

9. Renal function: Cr ≤ 1.5 × ULN, and creatinine clearance ≥ 45ml/min (calculatedaccording to Cockcroft-Gault formula);

10. Coagulation function: activated partial thromboplastin time (APTT) ≤ 1.5 × ULN,prothrombin time (PT) ≤ 1.5 × ULN, international normalized ratio (INR) ≤ 1.5 ×ULN; 10.Eligible patients of childbearing potential (men and women) must agreeto use a reliable method of contraception (hormonal or barrier method orabstinence) during the trial and for at least 90 days after the last dose;female patients of childbearing potential must have a negative blood pregnancytest within 7 days prior to enrollment.

Exclusion Criteria:

1. received chemotherapy, radiotherapy, biological therapy, endocrine therapy,targeted therapy, immunotherapy and other anti-tumor drugs within 4 weeksbefore the first use of the study drug, of which oral fluorouracil and smallmolecule targeted drugs were within 2 weeks before the first use of the studydrug or within 5 half-lives of the drug (whichever was longer).

2. Patients who have received transcatheter arterial chemoembolization (TACE)within 4 weeks before the first use of the study drug.

3. Received other clinical trial drugs that are not approved for marketing within 4 weeks before the first use of the study drug.

4. Major organ surgery (excluding needle biopsy) or significant trauma within 4weeks before the first dose of study drug.

5. Have received a vaccine within 4 weeks prior to the first dose of study drug.

6. Patients who have received systemic corticosteroids (prednisone > 10 mg/day orequivalent doses of the same class of drugs) or other immunosuppressive agentswithin 14 days before the first dose of study drug; except for the following:topical, ocular, intra-articular, intranasal, and inhaled corticosteroids;short-term corticosteroids (≤ 10 mg prednisone equivalent) for prophylaxis (e.g., prevention of contrast agent allergy).

7. The adverse reactions of previous anti-tumor treatment have not recovered toCTCAE 5.0 grade evaluation ≤ 1 (except alopecia and other toxicities that arejudged by the investigator to have no safety risk); 8. Patients with centralnervous system metastasis, spinal cord metastasis and/or spinal cordcompression.

8. in the herpes simplex virus recurrence and infection period, and there arecorresponding clinical manifestations, such as oral herpes labialis, herpetickeratitis, herpetic dermatitis, genital herpes and so on.

9. other active uncontrolled infections. 11. History of immunodeficiency,including positive HIV antibody test and positive Treponema pallidum antibodytest.

10. Patients with active chronic hepatitis B or active hepatitis C. (Excepthepatitis B virus carriers, hepatitis B virus stable after drug treatment [HBV-DNA negative or < 500 IU/ml] and cured hepatitis C patients [HCV RNAnegative]) 13. History of serious cardiovascular disease:

11. Ventricular arrhythmia requiring clinical intervention;

12. QTc interval > 480 ms;

13. Acute coronary syndrome, congestive heart failure, stroke or other Grade IIIand above cardiovascular events within 6 months before the first use of studydrugs;

14. New York Heart Association (NYHA) functional classification ≥ II or leftventricular ejection fraction (LVEF) < 40%;

15. Uncontrolled hypertension after treatment (judged by the investigator); 14.Patients with active, or have had and have the possibility of relapse ofautoimmune diseases (such as systemic lupus erythematosus, rheumatoidarthritis, vasculitis, etc.); except for clinically stable autoimmunethyroiditis, autoimmune-mediated hypothyroidism treated with stable doses ofthyroid replacement hormone, type I diabetes treated with stable doses ofinsulin, vitiligo or recovered childhood asthma/allergy, without anyintervention in adults.

16. Having received immunotherapy and have experienced immune-related adverseevents (irAEs) such as immune-related pneumonia and myocarditis, which mayaffect the safety of the investigational drug as judged by the investigator.

17. Known alcohol or drug dependence. 17. Patients with mental disorders or poorcompliance. 18. Pregnant or lactating women. 19. The investigator believes thatthe subject has other serious systemic diseases or other reasons and is notsuitable for this clinical study.