Advanced Hepatocellular Carcinoma
Conditions
Interventions
Control Arm:Regorafenib
Arm 2: SH006 Injection + Bevacizumab:SH006+Bevacizumab Combinative administration
Arm 3:SH006+Oxaliplatin+Capecitabine Combinative administration
Arm 1:SH006+Bevacizumab+Oxaliplatin+Capecitabine Combinative administration
Sponsors
Nanjing Tianyinshan Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. The subjects are able to understand the informed consent form, voluntarily participate and sign the informed consent form; 2. Age range is 18 to 75 years old (inclusive) (based on the day of signing the informed consent form), regardless of gender; 3. Patients with hepatocellular carcinoma confirmed by histopathology or clinical diagnosis (according to the Guidelines for Diagnosis and Treatment of Primary Liver Cancer (National Health Commission, 2024 Edition)); 4. Barcelona Clinic Liver Cancer (BCLC) Stage C, or Stage B not suitable for curative surgery and/or locoregional therapy; 5. Previously failed at least one line of therapy containing an immune checkpoint inhibitor; 6. At least one measurable lesion according to RECIST 1.1 criteria: a lesion accurately measured by computed tomography (CT) or magnetic resonance imaging (MRI) (preferably with intravenous contrast) as having a long diameter >=10 mm (except lymph nodes, which must have a short axis >=15 mm), and suitable for repeated measurement. For lesions previously treated with radiotherapy, intervention, or ablation, there must be documented evidence of definite progression at the site, meeting the RECIST 1.1 criteria for measurable lesions; 7. Child-Pugh score = 3 months as judged by the investigator; 10. Organ function levels must meet the following requirements (no blood transfusion, blood products, or hematopoietic growth factors for correction within 14 days prior to screening): a. Hematology: Absolute Neutrophil Count (ANC) >=1.5×10?/L, Platelets (PLT) >=75×10?/L, Hemoglobin (Hb) >=90 g/L; b. Liver Function: Albumin (ALB) >=28 g/L, Total Bilirubin (TBIL) =2+, a 24-hour urine collection should be performed, and the 24-hour urine protein quantification must be <1 g. 11. For subjects positive for Hepatitis B Surface Antigen (HBsAg), HBV DNA must be <2000 IU/mL, and they must receive continuous antiviral therapy. Those not previously on antiviral therapy should initiate it 1 week before the first dose or during the study (e.g., Entecavir, Tenofovir Disoproxil Fumarate, etc.). For subjects positive for Hepatitis C Antibody (HCV-Ab), HCV RNA must be below the lower limit of detection. 12. Female subjects of childbearing potential must use effective contraception during the trial and for 6 months after the last dose, with a negative pregnancy test within 7 days before treatment initiation. Male subjects must use effective contraception from signing the informed consent form until 6 months after the last dose. 13. Subjects must have the ability and willingness to comply with the visits, treatment plans, laboratory tests, and other study-related procedures stipulated in the protocol.
Exclusion criteria
Exclusion criteria: 1. Patients with a previous histological diagnosis of intrahepatic cholangiocarcinoma (ICC), combined hepatocellular-cholangiocarcinoma (cHCC-CCA), fibrolamellar hepatocellular carcinoma, or sarcomatoid hepatocellular carcinoma; or patients diagnosed with diffuse liver cancer; 2. Tumor thrombus in the portal vein involving the main portal trunk, or involving both the main trunk and the superior mesenteric vein; or tumor thrombus in the inferior vena cava; 3. History of hepatic encephalopathy; history of liver transplantation; 4. Presence of central nervous system metastases; 5. Clinically symptomatic moderate or severe ascites requiring therapeutic paracentesis or drainage (except for those with only imaging findings of minimal ascites and no clinical symptoms), or uncontrolled or moderate/sepleural effusion, or pericardial effusion; 6. Received anti-tumor surgery within 3 months prior to the first dose in this trial; received interventional therapy, radiotherapy, or ablation therapy within 4 weeks prior to the first dose (palliative radiotherapy for bone metastases within 2 weeks prior to the first dose is allowed); underwent procedures such as puncture drainage or tissue biopsy within 1 week prior to the first dose; 7. Received chemotherapy within 3 weeks, or targeted therapy, endocrine therapy, or immunotherapy within 4 weeks prior to the first dose in this trial, with the following exceptions: use of mitomycin or nitrosoureas within 6 weeks prior to the first dose; use of oral fluoropyrimidines (e.g., Tegafur/Gimeracil/Oteracil Potassium [S-1], Capecitabine) and small-molecule targeted agents within 2 weeks prior to the first dose; use of any Chinese patent medicine indicated for liver cancer (including modern Chinese medicine preparations with liver cancer indications: Akliding Capsules, Delisheng Injection, Kanglaite Injection or Soft Capsules, Aidi or Kangsai Di Injection, Xiaoaiping [Tongguanteng], Elemente, Huaier Granules, and Ganfule Tablets) within 2 weeks prior to the first dose; 8. Prior treatment with anti-TIGIT therapy; 9. Presence of toxicities from previous treatments that have not recovered to <= Grade 1 per CTCAE v5.0 or to baseline levels (except for toxicities deemed by the investigator to pose no safety risk, such as alopecia, hypothyroidism manageable with hormone replacement therapy, etc.); 10. Presence of active infection (e.g., acute bacterial infection, active syphilis, or active human immunodeficiency virus [HIV] infection); 11. Active bleeding or coagulation disorders, bleeding tendency, or receiving thrombolytic, anticoagulant, or antiplatelet therapy; 12. History of gastrointestinal bleeding within 6 months prior to the first dose, or clear tendency for gastrointestinal bleeding, such as known history of locally active ulcer; subjects with fecal occult blood ++ or above are ineligible; if fecal occult blood is persistently +, or CT suggests the presence of gastroesophageal varices, or the investigator deems gastroscopy necessary, gastroscopy should be performed; or presence of severe gastroesophageal varices; 13. History of gastrointestinal perforation and/or fistula within the past 6 months; history of perforation or fistula at other sites; 14. Diagnosis of any other malignancy within the past 5 years (except for radically resected and non-recurrent skin basal cell carcinoma, skin squamous cell carcinoma, superficial or non-invasive bladder cancer, localized prostate cancer, carcinoma in situ of the cerv
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-Free Survival (PFS) ;Safety Assessment; | — |
Secondary
| Measure | Time frame |
|---|---|
| Immunogenicity Evaluation Endpoints;Overall survival;Pharmacokinetic (PK) Evaluation Endpoints; | — |
Countries
China
Contacts
Public ContactFeng Liao
Nanjing Tianyinshan Hospital
Outcome results
None listed