A Single-Arm, Multicenter, Open-Label Phase IIa Clinical Study to Evaluate the Efficacy and Safety of VG161 in the Treatment of Advanced Intrahepatic Cholangiocarcinoma
VG161 is a recombinant human-IL12/15/PDL1B oncolytic HSV-1 Injectable. This trial is a single-agent, single-arm, multicenter, open-label design clinical trial for advanced intrahepatic cholangiocarcinoma who have failed standard therapy. To evaluate the efficacy of VG161 administered by ultrasound or CT-guided intratumoral injection in patients with advanced intrahepatic cholangiocarcinoma, with the primary outcome measure being objective response rate (ORR).
• 1\. Subjects must fully understand and give informed consent to this study before the trial, and voluntarily sign a written informed consent form.
• 2\. aged 18 to 75 years (inclusive), male or female. 3. patients with histologically or cytologically confirmed advanced intrahepatic cholangiocarcinoma.
• 4\. According to the Guidelines for the Diagnosis and Treatment of Biliary Malignant Tumors (CSCO), patients must have previously received at least systemic first-line therapy for advanced intrahepatic cholangiocarcinoma and failed, or cannot tolerate treatment. Patients who received preoperative neoadjuvant chemotherapy or postoperative adjuvant chemotherapy were counted as having failed first-line treatment if disease progression occurred during chemotherapy or within 6 months after stopping chemotherapy; 5. According to RECIST 1.1 criteria, one or more CT examinations are determined to be measurable and meet the requirements for the volume administered for the first injection, tumor lesions and/or metastases (the injected lesions should preferably be the main tumor burden lesions) that can be injected under ultrasound or CT guidance, and the baseline longest diameter of the injected lesions (lymph node lesions are short diameters) is \> 1.5 cm.
• 6\. Herpes simplex virus type I (HSV-1) antibody test results (HSV-1 IgG or HSV-1 IgM) are positive.
• 7\. ECOG performance score 0-1. 8. Expected survival time of more than 3 months. 9.Adequate organ function:
⁃ Blood routine (no blood transfusion or colony-stimulating factor treatment within 14 days): ANC ≥ 1.5 × 109/L, PLT ≥ 75 × 109/L, Hb ≥ 85 g/L;
⁃ Liver function: TBIL ≤ 1.5 × ULN, ALT ≤ 3 × ULN, AST ≤ 3 × ULN;
⁃ Child-Pugh A-B;
⁃ Renal function: Cr ≤ 1.5 × ULN, and creatinine clearance ≥ 45ml/min (calculated according to Cockcroft-Gault formula);
⁃ 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 agree to use a reliable method of contraception (hormonal or barrier method or abstinence) during the trial and for at least 90 days after the last dose; female patients of childbearing potential must have a negative blood pregnancy test within 7 days prior to enrollment.