Advanced hepatocellular carcinoma
Conditions
Interventions
SH006 Injection + Bevacizumab group:The combined administration of SH006 Injection and Bevacizumab
SH006 Injection + Oxaliplatin + Capecitabine group:H006 Injection + Oxaliplatin + Capecitabine Combination Regimen
SH006 Injection + Bevacizumab + Oxaliplatin + Capecitabine group:Combined administration of SH006 Injection, Bevacizumab, Oxaliplatin and Capecitabine
Sponsors
Zhongshan Hospital, Fudan University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1.The subject is capable of understanding the informed consent form, voluntarily participates in the study, and signs the informed consent form. 2.The subject is aged between 18 and 75 years old (inclusive), as determined on the day of signing the informed consent form, regardless of gender. 3.The subject is a patient with hepatocellular carcinoma confirmed by histopathological or clinical diagnosis according to the Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2024 Edition, National Health Commission). 4.The subject is at Barcelona Clinic Liver Cancer (BCLC) stage C, or at stage B but not suitable for radical surgical treatment and/or local treatment. 5.The subject has previously failed treatment with a regimen containing an immune - checkpoint inhibitor. 6.According to the RECIST 1.1 criteria, the subject has at least one measurable lesion. The long diameter of the lesion, accurately measured by computed tomography (CT) or magnetic resonance imaging (MRI) (preferably with intravenous contrast agent), should be >= 10 mm (except for lymph nodes, where the short axis must be >= 15 mm), and the lesion is suitable for repeated measurement. For lesions that have previously undergone radiotherapy, interventional therapy, or ablation, there must be evidence of clear progression at the site, and the lesion should meet the criteria of a measurable lesion according to RECIST 1.1. 7.The subject has a Child - Pugh score = 3 months; 10. Organ function levels must meet the following requirements (no blood transfusion or blood products within 14 days prior to screening, and no use of hematopoietic-stimulating factor correction): (1) Complete blood count: Absolute neutrophil count (ANC) > = 1.5×10^9/L, platelet count (PLT) > = 75×10^9/L, hemoglobin (Hb) > = 90 g/L; (2) Liver function: albumin (ALB) > = 28 g/L, total bilirubin (TBIL) =2 should have urine collection within 24 hours and a quantitative urine protein < 1g within 24 hours; 11. Patients positive for hepatitis B surface antigen (HBsAg) require HBV DNA < 2000 IU/mL and complete antiviral therapy. Those who have not previously received antiviral therapy should receive antiviral therapy one week before dosing or during the study (e.g., entecavir, tenofovir fumarate modal, etc.); In cases of hepatitis C antibody (HCV-Ab) positivity, HCV RNA is below the lower detection threshold; 12. Female subjects of childbearing age should use effective contraception during the trial period and within 6 months after the last dose, and a negative pregnancy test within 7 days before starting treatment; Male subjects used effective contraception from the date of signing informed consent until 6 months after the last dose; 13. Subjects are able and willing to comply with visits, treatment plans, laboratory tests, and other study-related procedures as stipulated in the study protocol.
Exclusion criteria
Exclusion criteria: 1.Prior histological confirmation of intrahepatic cholangiocarcinoma (ICC), combined hepatocellular-cholangiocarcinoma (cHCC-CCA), fibrolamellar HCC, or sarcomatoid HCC; or diagnosis of diffuse HCC. 2.Portal vein tumor thrombus involving the main trunk, or concurrent involvement of the main trunk and superior mesenteric vein; inferior vena cava tumor thrombus; 3.History of hepatic encephalopathy or liver transplantation; 4.Presence of central nervous system metastases; 5.Clinically significant moderate/severe ascites requiring therapeutic paracentesis (excluding asymptomatic minimal ascites on imaging only), or uncontrolled/moderate-to-severe pleural/pericardial effusion; 6.Anticancer surgery within 3 months prior to first dose; interventional/radiotherapy/ablation within 4 weeks (except palliative bone radiotherapy within 2 weeks); puncture drainage/biopsy within 1 week; 7.Chemotherapy within 3 weeks prior to first dose; targeted/endocrine/immunotherapy within 4 weeks (exceptions: mitomycin/nitrosoureas within 6 weeks; oral fluoropyrimidines/small-molecule TKIs within 2 weeks; any TCM with HCC indication within 2 weeks); 8.Prior exposure to anti-TIGIT agents; 9.Persistent toxicity >CTCAE v5.0 Grade 1 or baseline from prior therapy (except non-safety risks like alopecia/hypothyroidism with hormone replacement; 10.Active infection (e.g., acute bacterial infection, active syphilis/HIV; 11.Active bleeding, coagulopathy, bleeding diathesis, or ongoing anticoagulant/antiplatelet therapy; 12.GI bleeding within 6 months or high bleeding risk (e.g., active ulcer, fecal occult blood =++; mandatory endoscopy for persistent occult blood+/esophageal varices; 13.GI perforation/fistula within 6 months; other perforation/fistula history; 14.Other malignancy within 5 years (except cured basal/squamous cell skin cancer, superficial bladder cancer, localized prostate/cervical/ductal breast cancer, papillary thyroid cancer; 15. Suffering from severe cardiovascular and cerebrovascular diseases, including but not limited to the following: (1) Acute myocardial infarction or unstable angina within 6 months prior to the first dose, and who have undergone coronary angioplasty or coronary stent implantation; (2) Cerebrovascular accident or transient ischemic attack occurring within 6 months prior to the first dose; (3) Other arteriovenous thromboembolic events occurring within 6 months prior to the first dose, including pulmonary artery embolism, deep vein thrombosis, or other serious thromboembolic events; Except for implantable intravenous port or duct-derived thrombosis, or superficial venous thrombosis stabilized after conventional anticoagulant therapy. Low-dose low-molecular-weight heparin (e.g., enoxaparin 40 mg/day) is allowed for prophylactic use; (4) New York Heart Association Class II to IV congestive heart failure or left ventricular ejection fraction (LVEF) =100 mmHg) despite optimal treatment); (6) = grade 2 arrhythmias (CTCAE v5.0); (7) ECG QTcF interval prolongation (QTcF >480 ms); 16. History of autoimmune diseases, including but not limited to systemic lupus erythematosus, nephritis, rheumatoid arthritis, inflammatory bowel disease, autoimmune hepatitis (excluding the following: type 1 diabetes, skin diseases requiring no systemic treatment (such as vitiligo), controlled celiac disease, childhood asthma with complete resolution
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety-related observation results such as adverse events.;Progression-Free Survival (PFS);Overall Survival; | — |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy indicators (objective response rate, overall survival, duration of response, disease control rate, time to response, time to progression (TTP));Pharmacokinetic (PK) evaluation indicators (PK parameters, including but not limited to Tmax, Cmax, AUClast, Tmax,ss, Cmax,ss, AUCtau,ss, t1/2, MRT, Vz, and CLz); | — |
Countries
China
Contacts
Public ContactWang Peng
Zhongshan Hospital, Fudan University
Outcome results
None listed